[Guideline adherence and quality assurance in radiological diagnostics in cases of suspected child abuse in Germany]. / Leitlinientreue und Qualitätssicherung in der bildgebenden Diagnostik bei Verdacht auf Kindesmisshandlung in Deutschland.

BACKGROUND: Diagnostic imaging plays a key role in the evaluation of non-accidental consequences of injuries in childhood. Fractures are the second most common consequence of child abuse, after skin lesions such as abrasions or bleeding. With the evidence of radiological criteria, non-accidental fractures can be differentiated from accidental fractures. Special types of fractures such as the classic metaphyseal lesion can only be differentiated if the image quality is high. AIM: The goal of this prospective study was to assess adherence to guidelines and quality assurance of radiological diagnostics in the event of suspected abuse in Germany. For this purpose, the quantity and diagnostic quality in university and non-university hospitals as well as the existence of a pediatric radiology department were analyzed. MATERIALS AND METHODS: In all, 958 X­ray examinations of 114 suspected abuse cases (46 girls, 68 boys) were evaluated; 42 cases from university, 42 from maximum care and 30 from regular care clinics with a median age of 6 months (3 weeks-3 years of age) were assessed as DICOM data by 3 pediatric radiologists in a consensus procedure with regard to adherence to guidelines and various quality parameters. An accompanying questionnaire was used to compare the theoretical knowledge with the respective practical implementation. RESULTS: A mean of 8.4 X­rays (range 1-22) were made per case. In 12 of 114 assessed cases (10%) there was a complete skeletal status according to the S1 guideline. A babygram was performed in 13 cases (10.5%). Departments with focus on pediatric radiology produced significantly more X­rays per skeletal status than facilities without this specialization (p < 0.04). Significantly higher qualitative implementation was recorded in university hospitals (p < 0.001). Regardless of the type of institution, there was only marginal agreement between the questionnaire response and the available image material. CONCLUSION: In Germany, a guideline-compliant procedure in the event of suspected child abuse is largely lacking. It remains to be seen whether this will change in the future with the broader implementation of child protection groups and the S3+ child protection guideline adopted in 2019 (AWMF register 027-069). The establishment of reference centers for a second diagnosis and recommendations for imaging technology can also improve the quality of care over the long term.

Assessment of histological response of paediatric bone sarcomas using FDG PET in comparison to morphological volume measurement and standardized MRI parameters.

PURPOSE: The objective of this study was to evaluate positron emission tomography (PET) using (18)F-fluoro-2-deoxy-D-glucose (FDG) in comparison to volumetry and standardized magnetic resonance imaging (MRI) parameters for the assessment of histological response in paediatric bone sarcoma patients. METHODS: FDG PET and local MRI were performed in 27 paediatric sarcoma patients [Ewing sarcoma family of tumours (EWS), n = 16; osteosarcoma (OS), n = 11] prior to and after neoadjuvant chemotherapy before local tumour resection. Several parameters for assessment of response of the primary tumour to therapy by FDG PET and MRI were evaluated and compared with histopathological regression of the resected tumour as defined by Salzer-Kuntschik. RESULTS: FDG PET significantly discriminated responders from non-responders using the standardized uptake value (SUV) reduction and the absolute post-therapeutic SUV (SUV2) in the entire patient population (SUV, p = 0.005; SUV2, p = 0.011) as well as in the subgroup of OS patients (SUV, p = 0.009; SUV2, p = 0.028), but not in the EWS subgroup. The volume reduction measured by MRI/CT did not significantly discriminate responders from non-responders either in the entire population (p = 0.170) or in both subgroups (EWS, p = 0.950; OS, p = 1.000). The other MRI parameters alone or in combination were unreliable and did not improve the results. Comparing diagnostic parameters of FDG PET and local MRI, metabolic imaging showed high superiority in the subgroup of OS patients, while similar results were observed in the population of EWS. CONCLUSION: FDG PET appears to be a useful tool for non-invasive response assessment in the group of OS patients and is superior to MRI. In EWS patients, however, neither FDG PET nor volumetry or standardized MRI criteria enabled a reliable response assessment to be made after neoadjuvant treatment.

Early and late therapy response assessment with [18F]fluorodeoxyglucose positron emission tomography in pediatric Hodgkin's lymphoma: analysis of a prospective multicenter trial.

PURPOSE: In adult Hodgkin's lymphoma (HL) risk stratification after early therapy response assessment with [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) seems to allow tailoring therapy with less toxicity for patients with adequate metabolic response. This study delivers the first prospective data on the potential of FDG-PET for response assessment in pediatric HL. PATIENTS AND METHODS: FDG-PET was performed in 40 pediatric HL patients before polychemotherapy (PET-1), after two cycles of polychemotherapy (PET-2), and after completion of polychemotherapy (PET-3). Mean follow-up was 46 months (range, 26 to 72 months). RESULTS: At early and late response assessment, the proportion of PET-negative patients was significantly higher compared with those patients with negative findings in conventional imaging methods (CIMs; PET-2, 26 of 40 v CIM-2, one of 40; P < .001; PET-3, 21 of 29 v CIM-3, four of 29; P < .001). Sensitivity and negative predictive value were 100% for early and late therapy response assessment by PET. Both patients suffering a relapse during follow-up were identified by PET-2/3, whereas one of these patients was not detected by CIM-3. PET was superior to CIMs with regard to specificity in early and late therapy response assessment (68% v 3%, and 78% v 11%, respectively; both P < .001). Specificity of early therapy response assessment by PET was improved to 97% by quantitative analysis of maximal standardized uptake value reduction using a cutoff value of 58%. CONCLUSION: Pediatric HL patients with a negative PET in response assessment have an excellent prognosis while PET-positive patients have an increased risk for relapse.

Use of positron emission tomography for staging, preoperative response assessment and posttherapeutic evaluation in children with Wilms tumour.

PURPOSE: To evaluate FDG-PET for staging, grading, preoperative response assessment and posttherapeutic evaluation in children with Wilms tumour (WT). METHODS: In this study, 23 FDG-PET examinations in 12 paediatric patients (female, n = 5; male, n = 7; age, 1-19 years) with WT (primary, n = 9; relapsed, n = 3) were analysed. All patients were examined with conventional imaging methods (CIM) according to the SIOP2001/GPOH trial protocol. Additionally, FDG-PET/PET-CT was performed for staging (n = 12), preoperative response assessment (n = 6) and posttherapeutic evaluation (n = 5). Imaging results of FDG-PET and CIM were analysed regarding the accuracy in tumour visualisation, impact on therapeutic management and preoperative response assessment, with clinical follow-up and histopathology as the standard of reference. RESULTS: FDG-PET and CIM showed concordant results for staging of primary WT, whereas FDG-PET was superior in 1/3 cases with recurrent WT. Concerning histological differentiation, one case with anaplastic WT had an standard uptake value (SUV) of 12.3, which was remarkably higher than the average SUV in the eight cases with intermediate risk histology. No parameter analysed for PET or CIM was reliably predictive for histological regression or clinical outcome. After completion of therapy, FDG-PET was superior to CIM in 2/5 cases in detecting residual disease with therapeutic relevance. CONCLUSION: FDG-PET does not provide additional information to the traditional imaging work-up for staging WT patients, preoperative response assessment and clinical outcome. FDG-PET was advantageous in ruling out residual disease after completion of first line treatment and in pretherapeutic staging of relapse patients. Furthermore, there seems to be a good correlation of initial SUV and histological differentiation.

Positron emission tomography for staging of pediatric sarcoma patients: results of a prospective multicenter trial.

PURPOSE: The objective of this study was to evaluate the impact of positron emission tomography (PET) using fluorine-18-fluorodeoxyglucose (FDG) for initial staging and therapy planning in pediatric sarcoma patients. PATIENTS AND METHODS: In this prospective multicenter study, 46 pediatric patients (females, n = 22; males, n = 24; age range, 1 to 18 years) with histologically proven sarcoma (Ewing sarcoma family tumors, n = 23; osteosarcoma, n = 11; rhabdomyosarcoma, n = 12) were examined with conventional imaging modalities (CIMs), including ultrasound, computed tomography (CT), magnetic resonance imaging, and bone scintigraphy according to the standardized algorithms of the international therapy optimization trials, and whole-body FDG-PET. A lesion- and patient-based analysis of PET alone and CIMs alone and a side-by-side (SBS) analysis of FDG-PET and CIMs were performed. The standard of reference consisted of all imaging material, follow-up data (mean follow-up time, 24 +/- 12 months), and histopathology and was determined by an interdisciplinary tumor board. RESULTS: FDG-PET and CIMs were equally effective in the detection of primary tumors (accuracy, 100%). PET was superior to CIMs concerning the correct detection of lymph node involvement (sensitivity, 95% v 25%, respectively) and bone manifestations (sensitivity, 90% v 57%, respectively), whereas CT was more reliable than FDG-PET in depicting lung metastases (sensitivity, 100% v 25%, respectively). The patient-based analysis revealed the best results for SBS, with 91% correct therapy decisions. This was significantly superior to CIMs (59%; P < .001). CONCLUSION: In staging pediatric sarcoma, subsidiary FDG-PET scanning depicts important additional information and has a relevant impact on therapy planning when analyzed side-by-side with CIMs.

Brain morphology alterations in the basal ganglia and the hypothalamus following prenatal exposure to antiepileptic drugs.

If humans are exposed prenatally to antiepileptic drugs (AEDs), cognitive impairment may be the consequence. Driven by results of experimental work showing that AEDs may induce neuronal death in the developing rodent brain, we wanted to explore whether prenatal exposure to AEDs (PAE) may result in structural changes in the human brain. For this purpose we investigated a group of healthy young adults with PAE and a group of age-matched unexposed healthy controls by magnetic resonance imaging (MRI) of the brain. Local differences in cerebral morphology associated with PAE were analysed in volumetric MRI data by use of voxelwise comparisons of grey and white matter images. Significant regional decreases of grey matter volumes were found in PAE subjects in the area of the lentiform nucleus, including both pallidum and putamen bilaterally, and the hypothalamus. No significant regional differences in white matter volumes were found. We conclude that PAE causes subtle morphological changes in grey matter of the human brain which are conform with lower cell numbers in the basal ganglia and the hypothalamus.

Correlative imaging strategies implementing CT, MRI, and PET for staging of childhood Hodgkin disease.

BACKGROUND: The value of different correlative imaging strategies with F18-fluorodeoxyglucose positron emission tomography (FDG-PET) and conventional imaging modalities (CIM) for initial staging of pediatric Hodgkin disease (HD) was assessed. METHODS: Thirty-three patients (age, 4 to 18 y) with histologically proven HD underwent initial staging with computed tomography (thorax), magnetic resonance imaging (neck, abdomen, pelvis), and FDG-PET in a prospective study. Image fusion (PET-CIM) was performed using a semiautomatic voxel-based algorithm. Analysis of separate, side-by-side (SBS) and fused PET and CIM was performed evaluating 21 nodal and 6 extranodal regions per patient for presence of lymphoma, applying a 5-point confidence scale. The reference data was clinical follow-up (>12 mo). RESULTS: Concerning lymph node regions above and below the diaphragm the accuracy of CIM, PET, SBS, and image fusion was 86%, 89%, 94%, 97%, and 94%, 94%, 97%, 98%. In extranodal regions, the accuracy was 96%, 96%, 100%, and 100%. The reviewers' confidence was improved significantly by image fusion. Staging and therapy assignment on the basis of CIM was correctly modified by SBS in 5 and 4, by image fusion in 7 and 5 patients. CONCLUSIONS: Combined reading of FDG-PET and CIM is crucial for accurate staging in pediatric HD. Image fusion improves the observers' confidence and has impact on the therapeutic management.

Melorheostosis of the hand in a 7-year-old girl.

Melorheostosis of the hand is rare. We report a 7-year-old girl who presented with a contracture of the left hand. Diagnosis was made by conventional radiography and bone scintigraphy. MRI proved to be a very useful tool to visualize the soft-tissue changes. This is especially important when surgical repair is considered.

Ehlers-Danlos syndrome type VI with cystic malformations of the meninges in a 7-year-old girl.

UNLABELLED: A 7-year-old girl with thoracolumbar kyphoscoliosis was admitted for further diagnostic evaluation after a spinal MRI scan had shown several intraspinal extramedullary lesions. The clinical features including joint hypermobility and cigarette-paper like scars led to the presumptive diagnosis of Ehlers-Danlos syndrome type VI (EDS VI). Analysis of urinary lysyl- and hydroxylysyl-pyridinoline cross-links excretion confirmed a deficiency of lysylhydroxylase 1 and the diagnosis of EDS VIA. Findings on the spinal MRI scan were interpreted as spinal meningeal cysts. Over a period of 2 years, the patient developed no neurological deficits and no radiological signs of progression of the spinal lesions. CONCLUSION: We assume cystic malformations of the meninges to be most likely the result of connective tissue weakness in Ehlers-Danlos syndrome type VI.

Brachydactyly type C caused by a homozygous missense mutation in the prodomain of CDMP1.

Brachydactyly type C (BDC) is characterized by shortening of the middle phalanges of the index, middle, and little finger with hyperphalangy, usually of the index and middle finger. Heterozygous mutations of the cartilage derived morphogenetic protein-1 (CDMP1) resulting in a loss of function have been reported in BDC. We here describe a large kindred with a semi-dominant form of BDC and pronounced ulnar deviation of the second and third digits. In this family a novel homozygous missense mutation was identified (517A > G) changing methionine to valine at amino acid position 173. The mutation is located within a highly conserved seven amino acid region of the prodomain of CDMP1. Hand radiographs of heterozygous mutation carriers showed mild shortening of the metacarpals IV and V; a finding confirmed by the analysis of their metacarpophalangeal profiles (MCPPs). The mutation described here points toward an important function of the prodomain for the folding, secretion, and availability of biologically active CDMP1.

Survival to adulthood and dominant inheritance of platyspondylic skeletal dysplasia, Torrance-Luton type.

We present a second family with survival to adulthood and dominant transmission of the Torrance-Luton type of platyspondylic chondrodysplasia, and demonstrate the radiographs at different ages together with radiographs and further data of the first family which was published in the Journal of Pediatrics (J Pediatr 136:411-413). Two families are described with survival to adulthood and dominant transmission of the Torrance-Luton type of platyspondylic chondrodysplasia. Although lethality is increased in patients with this disorder, mild expressions of the genetic defect are compatible with survival into adulthood. The heterogeneous group of platyspondylic lethal skeletal dysplasias (PLSD) originally included thanatophoric dysplasias (TD1/2: MIM 187600, 187100) as the most common forms of this condition, as well as TD variants San Diego type (PLSD-SD: MIM 270230) and Torrance-Luton type (PLSD-TL: MIM 151210). Fibroblast growth factor receptor 3 ( FGFR3) gene mutations have been detected in TD1/2 and PLSD-SD. Molecular studies in one of our two families with the Torrance-Luton type did not disclose mutations in the FGFR3 coding region, suggesting that this type of platyspondylic chondrodysplasia is not a thanatophoric dysplasia variant. In contrast to TD1/2 and PLD-SD, the Torrance-Luton type platyspondylic dysplasia is compatible with survival to adulthood.

Homozygous and double heterozygous Factor V Leiden and Factor II G20210A genotypes predispose infants to thromboembolism but are not associated with an increase of foetal loss.

Prospective and controlled data about the individual risk profile in asymptomatic children with homozygous or double heterozygous risk genotypes for Factor V Leiden (FVL) and factor II (FII) G20210A are currently unavailable. The systematic and prospective observational study presented here was designed to determine the impact of the homozygous and double heterozygous FVL and FII G20210A genotypes on the prenatal and postnatal risk profiles of affected children. Risk infants and heterozygous controls were identified by screening of 85,304 neonates. Follow-up included the comparison of prenatal and postnatal development, ultrasonography of brain and kidneys, and a panel of independent determinants of thrombophilia. The numbers of identified or expected FVL homozygotes and double heterozygotes did not differ significantly (FVL: 116 versus 91, p=0.08; FVL/FII: 94 versus 76, p=0.17), indicating the absence of a prenatal disadvantage. A prenatal advantage was suggested in FII homozygotes, whose identified number far exceeded the expected (19 versus 4, p=0.002). Clinical and/or imaging abnormalities indicated spontaneous thromboembolic events in 4 of 129 risk infants (3%) but in none of the 178 controls (p=0.02). Physical and neurological development was normal in both groups during the first 2 years of life. The risk genotypes appear to confer a significant predisposition for spontaneous thromboembolic events in infancy without impeding development within the first two years of life. Foetal risk genotypes do not cause an increased foetal loss rate. Moreover, homozygous FII G20210A appears to be associated with a prenatal advantage.

Cerebral manifestations, hemihypertrophy and lymphoedema of one leg in a child with epidermal nevus syndrome (Schimmelpenning-Feuerstein-Mims).

The report focuses on a rare variant form of epidermal nevus syndrome (ENS) (Schimmelpenning-Feuerstein-Mims syndrome) describing lesions involving the skin, eyes, skeleton, heart and brain in an 11-year-old boy. Despite his evident brain pathology, the boy lacks neurological symptoms and mental retardation. We describe his unusual MRI appearances and radiographic skeletal findings. To our knowledge this is the first report of ENS with lymphoedema occurring together in the same individual.