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Shape analysis of infant's heads is crucial to diagnose cranial deformities and evaluate head growth. Currently available 3D imaging systems can be used to create 3D head models, promoting the clinical practice for head evaluation. However, manual analysis of 3D shapes is difficult and operator-dependent, causing inaccuracies in the analysis. This study aims to validate an automatic landmark detection method for head shape analysis. The detection results were compared with manual analysis in three levels: (1) distance error of landmarks; (2) accuracy of standard cranial measurements, namely cephalic ratio (CR), cranial vault asymmetry index (CVAI), and overall symmetry ratio (OSR); and (3) accuracy of the final diagnosis of cranial deformities. For each level, the intra- and interobserver variability was also studied by comparing manual landmark settings. High landmark detection accuracy was achieved by the method in 166 head models. A very strong agreement with manual analysis for the cranial measurements was also obtained, with intraclass correlation coefficients of 0.997, 0.961, and 0.771 for the CR, CVAI, and OSR. 91% agreement with manual analysis was achieved in the diagnosis of cranial deformities. Considering its high accuracy and reliability in different evaluation levels, the method showed to be feasible for use in clinical practice for head shape analysis.

Das Strategiepapier der GPR zeigt Entwicklungsmöglichkeiten der Kinder- und Jugendradiologie als Querschnittsfach zwischen der Radiologie und der konservativen und operativen Kinder- und Jugendmedizin auf. Zitierweise

Glutaric aciduria type 1 is a rare inherited neurometabolic disorder of lysine metabolism caused by pathogenic gene variations in GCDH (cytogenic location: 19p13.13), resulting in deficiency of mitochondrial glutaryl-CoA dehydrogenase (GCDH) and, consequently, accumulation of glutaric acid, 3-hydroxyglutaric acid, glutaconic acid and glutarylcarnitine detectable by gas chromatography/mass spectrometry (organic acids) and tandem mass spectrometry (acylcarnitines). Depending on residual GCDH activity, biochemical high and low excreting phenotypes have been defined. Most untreated individuals present with acute onset of striatal damage before age 3 (to 6) years, precipitated by infectious diseases, fever or surgery, resulting in irreversible, mostly dystonic movement disorder with limited life expectancy. In some patients, striatal damage develops insidiously. In recent years, the clinical phenotype has been extended by the finding of extrastriatal abnormalities and cognitive dysfunction, preferably in the high excreter group, as well as chronic kidney failure. Newborn screening is the prerequisite for pre-symptomatic start of metabolic treatment with low lysine diet, carnitine supplementation and intensified emergency treatment during catabolic episodes, which, in combination, have substantially improved neurologic outcome. In contrast, start of treatment after onset of symptoms cannot reverse existing motor dysfunction caused by striatal damage. Dietary treatment can be relaxed after the vulnerable period for striatal damage, that is, age 6 years. However, impact of dietary relaxation on long-term outcomes is still unclear. This third revision of evidence-based recommendations aims to re-evaluate previous recommendations (Boy et al., J Inherit Metab Dis, 2017;40(1):75-101; Kolker et al., J Inherit Metab Dis 2011;34(3):677-694; Kolker et al., J Inherit Metab Dis, 2007;30(1):5-22) and to implement new research findings on the evolving phenotypic diversity as well as the impact of non-interventional variables and treatment quality on clinical outcomes.

Acquired polyneuropathies (PN) are rare in childhood and adolescent. We report on a 15-year-old male patient who presented with progressive gait instability, ataxia, neuropathic pain, distal muscle weakness and progressive loss of ambulation. Nerve conduction studies (NCS) revealed a progressive demyelinating sensorimotor polyneuropathy predominantly of the lower limbs. Cerebrospinal fluid (CSF) analyses revealed a cytoalbuminologic dissociation. Extensive diagnostic workup for autoantibodies and inflammatory markers was inconclusive. Corticosteroids and intravenous immunoglobulins did not affect. Cranial MRI revealed leptomeningeal enhancement of the cerebellum and the brainstem. Brain biopsy of the cerebellar lesions revealed an unclassifiable sarcoma. The patient was treated according to the CWS guidance study resulting in a decrease in enhanced lesion size. After two years NCS still revealed a demyelinating sensorimotor PN. This case report describes for the first time the clinical course of a chronic PN, putative paraneoplastic, associated with isolated unclassifiable CNS-sarcoma in an adolescent patient. Paraneoplastic pathogenesis should be considered in an unusual sequence of subacute progressive neurological symptoms even in children and adolescents.

ZusammenfassungIschämische Hirninfarkte sind im Kindesalter selten, können aber bei den betroffenen Individuen zu irreversiblen Schäden und einer schwerwiegenden Beeinträchtigung der Lebensqualität führen. Ein signifikanter Anteil der Infarkte im Kindesalter geht auf primäre ZNS Vaskulitiden (PACNS) zurück. Zur sicheren Diagnose müssen Differenzialdiagnosen, inklusive Systemerkrankungen die mit Vaskulitis einhergehen können ausgeschlossen werden. In Analogie zur Klassifikation der systemischen Vaskulitis, wird die PACNS nach dem Kaliber der betroffenen Gefäße eingeteilt. Die Diagnose und Einteilung erfolgt anhand der klinischen Präsentation, laborchemischer und bildgebender Untersuchungen, sowie Hirnbiospien im Falle von Kleingefäß ZNS Vaskulitiden. In Ermangelung prospektiver und kontrollierter klinischer Studien orientiert sich das therapeutische Vorgehen derzeit an kleinen Fallserien und Expertenempfehlungen. Die zur Verfügung stehende Medikamententherapie umfasst systemische Antikoagulation, hochdosierte Kortikosteroide und, wenn nötig, Cyclophosphamid zur Remissionsinduktion, sowie Basismedikamente zur Remissionserhaltung. Die Pathophysiologie der PACNS wird aktuell nur sehr inkomplett verstanden. Die Untersuchung und Entdeckung genetischer Ursachen wird jedoch zu einer Neuklassifikation und zielgerichteten und individualisierten Therapieoptionen beitragen. Um dies voranzutreiben sind nicht zuletzt aufgrund der Seltenheit der PACNS im Kindesalter internationale Kooperationen notwendig.

Background Neurological development is determined by brain growth. Methods to measure total brain volume (TBV) in clinical settings are limited. MR-imaging represents the gold-standard. Aims The present study tests the hypotheses that in infants without any brain pathology, TBV – as determined by MRI – can be accurately estimated by cranial volume (CrV), measured by 3D-laser scanning. In case of good correlation of CrV with TBV it was further tested, whether CrV can be also estimated by (I) head circumference (HC) or (II) by other technology than laser scanning. Study design & subjects To test the hypothesis, that TBV can be reliably estimated by CrV-measurement, data from routine MRI and 3D-laser-scanner measurements were analyzed in infants if no major structural brain anomaly was found in MR-imaging. To test whether CrV can be predicted by HC-measurements during infancy, data from routine follow-up visits were used from preterms born in a two year period. Preterms are invited for a routine follow-up visit (which includes laser scanning of the head) at an age of 3 months and, for further follow-ups at 6, 9 or 12 months. To compare accuracy of CrV measurement by other techniques, a puppet head was measured, using different 3D-measurement principles: (i) Structured light projection system, (ii) The non-invasive laser-shape-digitizer, and (iii) Structure-from-motion (SFM) technique. Outcome measures TBV was compared with CrV using a Passing-Bablok-Regression. To determine how well HC predicts CrV, the coefficient of determinant (R2) was calculated for each age group. Results CrV and TBV of 25 infants (median age 19 month, body weight of 11 kg) showed a median bias of −86.7 mm3 with a slightly smaller TBV (median of 1034.1 mm3, IQR 875.9 … 1179.8 mm3) than CrV (median 1092.2, IQR 950.5 … 1258.4 mm3). CrV was poorly estimated by HC, with R2 between 0.79 and 0.87 at 3 and 9 month of age respectively. For the non-invasive laser-shape-digitizer and the SFM-technique the accuracy was good (radial coordinate differences ±0.3 vs. ±0.5 mm). Conclusion The present study provides convincing evidence that CrV can be used to estimate TBV in routine care, whereas HC is a poor predictor of individual CrV.

Chronic nonbacterial osteomyelitis (CNO) is an inflammatory bone disorder that most frequently affects children and adolescents. Chronic recurrent multifocal osteomyelitis (CRMO) is a severe form of CNO, usually characterized by symmetrical inflammatory bone lesions and its waxing and waning character. Sometimes severe and chronic pain can significantly affect the quality of life and psychosocial development of individuals affected. In the absence of prospectively tested and widely accepted diagnostic criteria or disease biomarkers, CNO remains a diagnosis of exclusion, and infections, malignancy and other differentials require consideration (1). The pathophysiology of CNO is not fully understood, but imbalanced cytokine expression and increased inflammasome activation in monocytes from CNO patients contribute to a pro-inflammatory phenotype that contributes to bone inflammation (2). Currently, no medications are licensed for the use in CNO. Most patients show at least some response to nonsteroidal anti-inflammatory drugs, others require more aggressive treatment that can include corticosteroids, cytokine-blocking agents and/or bisphosphonates (3). While under the care of an experienced team and sufficient treatment, the prognosis is good, but some patients will develop sequalae which can include vertebral compression fractures (1)., Highlights • CNO is an autoinflammatory bone disorder mostly affecting children and adolescents. • Dysregulated cytokine expression and pathological activation of inflammasomes play a central role. • Treatment is based on experience from case series and expert consensus treatment plans. • Understanding the exact molecular pathophysiology will allow patient stratification and individualized treatment.

Human induced pluripotent stem cells (hiPSCs) hold great potential for modeling human diseases and the development of innovative therapeutic approaches. Here, we report on a novel, simplified differentiation method for forming functional osteoclasts from hiPSCs. The three-step protocol starts with embryoid body formation, followed by hematopoietic specification, and finally osteoclast differentiation. We observed continuous production of monocyte-like cells over a period of up to 9 weeks, generating sufficient material for several osteoclast differentiations. The analysis of stage-specific gene and surface marker expression proved mesodermal priming, the presence of monocyte-like cells, and of terminally differentiated multinucleated osteoclasts, able to form resorption pits and trenches on bone and dentine in vitro. In comparison to peripheral blood mononuclear cell (PBMC)-derived osteoclasts hiPSC-derived osteoclasts were larger and contained a higher number of nuclei. Detailed functional studies on the resorption behavior of hiPSC-osteoclasts indicated a trend towards forming more trenches than pits and an increase in pseudoresorption. We used hiPSCs from an autosomal recessive osteopetrosis (ARO) patient (BIHi002-A, ARO hiPSCs) with compound heterozygous missense mutations p.(G292E) and p.(R403Q) in CLCN7, coding for the Cl-/H+-exchanger ClC-7, for functional investigations. The patient's leading clinical feature was a brain malformation due to defective neuronal migration. Mutant ClC-7 displayed residual expression and retained lysosomal co-localization with OSTM1, the gene coding for the osteopetrosis-associated transmembrane protein 1, but only ClC-7 harboring the mutation p.(R403Q) gave strongly reduced ion currents. An increased autophagic flux in spite of unchanged lysosomal pH was evident in undifferentiated ARO hiPSCs. ARO hiPSC-derived osteoclasts showed an increased size compared to hiPSCs of healthy donors. They were not able to resorb bone, underlining a loss-of-function effect of the mutations. In summary, we developed a highly reproducible, straightforward hiPSC-osteoclast differentiation protocol. We demonstrated that osteoclasts differentiated from ARO hiPSCs can be used as a disease model for ARO and potentially also other osteoclast-related diseases. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Children : open access pediatrics journal 8(8), 687 (2021). doi:10.3390/children8080687 special issue: "Special issue "Neuromuscular disorders in children and adolescents" / special issue editor: Rudolf Korinthenberg, guest editor", Published by MDPI, Basel

Das Strategiepapier der GPR zeigt Entwicklungsmöglichkeiten der Kinder- und Jugendradiologie als Querschnittsfach zwischen der Radiologie und der konservativen und operativen Kinder- und Jugendmedizin auf. ZITIERWEISE: · Mentzel H, von Kalle T, Antoch G et al. Challenges in Pediatric Radiology – Strategies of the board of the German speaking Society of Pediatric Radiology. Fortschr Röntgenstr 2020; 192: 531 – 536.

Background The safety of gadolinium-based contrast agents is a hot topic in radiology. Purpose To evaluate the safety profile of gadobutrol during routine use. Material and Methods Prospective, non-interventional study in 80 centers in Germany. The primary outcome was the number of adverse drug reactions (ADR) following gadobutrol administration. Results A total of 3710 patients were included in the analysis, including 404 children (10.9%). A total of 6026 magnetic resonance imaging examinations of organs/organ systems and 872 magnetic resonance angiography examinations were performed. A total of 22 (0.59%) patients experienced at least one ADR. Nausea and vomiting were the most frequent ADRs, experienced by nine (0.24%) and three (0.08%) patients, respectively. One serious ADR was recorded (anaphylactoid reaction). No deaths were reported. Conclusion This non-interventional study in 3710 patients confirmed gadobutrol as a safe and reliable contrast agent in adults and children.

IgG4-related disease (IgG4-RD) is an inflammatory disorder characterized by tumor-like swelling in one or more organs, elevated serum IgG4 levels, and histological alterations with infiltration of IgG4-positive plasma cells. IgG4-RD is rare and likely underdiagnosed in children. We report a case of a 16-year-old girl with IgG4-positive colitis that developed weeks after IgG4-related ophthalmic disease and discuss diagnosis and treatment in the context of the literature available. Since the pathophysiology of IgG4-RD is unknown, treatment options are empiric and, for the most part, untargeted. Systemic corticosteroid treatment is the basis of anti-inflammatory treatment in IgG4-RD and induced early remission in our patient. During corticosteroid taper, the patient developed weight loss and intestinal inflammation. Histopathological assessment of the intestinal walls confirmed IgG4-positive colitis. Immune-modulating treatment with non-biologic (e.g., methotrexate (MTX) and mycophenolate mofetil) or biologic (rituximab) disease-modifying antirheumatic drugs has been reported in treatment refractory or corticosteroid-dependent patients. The patient responded to treatment with anti-inflammatory therapy with food rich in TGF-β2 (modulen) and MTX. This is one of the first pediatric patients reported with IgG4-related colitis extending the phenotype of pediatric IgG4-RD. International collaboration to prospectively document clinical presentation and treatment responses may help to further establish the phenotype and treatment options and to raise awareness for IgG4-RD.

Bakterielle Arthritiden (BA) im Kindes- und Jugendalter sind selten. Aus diesem Grund bestand lange ein quantitativer und qualitativer Datenmangel fur eine rationale Handlungsempfehlung. Dies hat sich in den letzten Jahren durch umfangreichere – auch randomisierte – Studien geandert. Die vorliegenden Empfehlungen basieren auf den Ergebnissen einer Expertendiskussion padiatrischer Infektiologen, Kinderorthopaden, Kinderradiologen und padiatrischer Rheumatologen, die im Rahmen der Worlitzer Konsensusgesprache vom 17.04.2016 bis 18.04.2016 stattfand. Dabei wurde statt der haufig ublichen Bezeichnung „septische Arthritis“ der Begriff „bakterielle Arthritis“ gewahlt, da die Kinder nicht zwangslaufig ein septisches Bild zeigen. Aufgrund der umfangreichen und detaillierten Literaturrecherche, die den Empfehlungen zugrunde liegt, wird die Arbeit in 2 Teilen publiziert: Der vorliegende Teil 2 fokussiert den Schwerpunkt Therapie; Teil 1 befasst sich schwerpunktmasig mit der Diagnose der BA. Gemas mittlerweile durchgefuhrten randomisierten Studien reicht eine Antibiotikatherapie mit – im Vergleich zu fruheren Empfehlungen – kurzerer Behandlungsdauer aus; der Stellenwert der Steroide ist noch nicht definitiv geklart. Bei den interventionellen Verfahren zeigte sich, dass die Notwendigkeit einer obligaten Arthrotomie nicht mehr aufrechtzuerhalten ist. Vielmehr reicht die arthroskopische Spulung oder sogar die alleinige – moglichst quantitative – Aspiration bei unkomplizierten Verlaufen aus.

Bakterielle Arthritiden (BA) im Kindes- und Jugendalter sind selten. Aus diesem Grund bestand lange ein quantitativer und qualitativer Datenmangel fur eine rationale Handlungsempfehlung. Dies hat sich in den letzten Jahren durch umfangreichere – auch randomisierte – Studien geandert. Die vorliegenden Empfehlungen basieren auf den Ergebnissen einer Expertendiskussion padiatrischer Infektiologen, Kinderorthopaden, Kinderradiologen und padiatrischer Rheumatologen, die im Rahmen der Worlitzer Konsensusgesprache vom 17.04.2016 bis 18.04.2016 stattfand. Dabei wurde statt der haufig ublichen Bezeichnung „septische Arthritis“ der Begriff „bakterielle Arthritis“ gewahlt, da die Kinder nicht zwangslaufig ein septisches Bild zeigen. Aufgrund der umfangreichen und detaillierten Literaturrecherche, die den Empfehlungen zugrunde liegt, wird die Arbeit in 2 Teilen publiziert: Der vorliegende Teil 1 fokussiert den Schwerpunkt Diagnostik, Teil 2 wird sich schwerpunktmasig mit der Therapie der BA befassen. In der Diagnostik der BA bleibt der mikrobiologische Erregernachweis essenziell, und die Magnetresonanztomographie hat sich als wichtigste bildgebende Untersuchung etabliert.

Objective.The autoinflammatory bone disorder chronic nonbacterial osteomyelitis (CNO) covers a wide clinical spectrum, ranging from mild self-limited presentations to chronically active or recurrent courses, which are then referred to as chronic recurrent multifocal osteomyelitis (CRMO). Little is known about treatment options and longterm outcomes. We investigated treatment responses and outcomes in children with CNO.Methods.A retrospective chart review was conducted in a tertiary referral center, covering 2004–2015. Disease activity was measured at 0, 3, 6, 12, and 24 months after treatment initiation, and at the last recorded visit.Results.Fifty-six patients with CNO were identified; 44 had multifocal CNO. Fifty percent of patients relapsed after a median of 2.4 years, and as few as 40% remained relapse-free after 5 years. Nonsteroidal antiinflammatory drugs were used as first-line treatment in 55 patients, inducing remission after 3 months in all individuals with relapse rates of 50% after 2 years. Further treatment included corticosteroids (n = 23), tumor necrosis factor-α (TNF-α) inhibitors (n = 7), and bisphosphonates (n = 8). While 47% of patients with CNO relapsed within 1 year after corticosteroid therapy, favorable outcomes were achieved with TNF-α inhibitors or bisphosphonates (pamidronate).Conclusion.CNO is a chronic disease with favorable outcomes within the first year, but high relapse rates in longterm followup. Particularly, patients with CRMO with long-lasting, uncontrolled inflammation were at risk for the development of arthritis. Our findings underscore the importance of a timely diagnosis and treatment initiation. Prospective studies are warranted to establish evidence-based diagnostic and therapeutic approaches to CNO.

Deformational plagiocephaly (DP) is an asymmetric flattening of the occiput, which can be caused by a preference for a sleeping position or a restriction of the head rotation. The absence of a standardized method to quantify the severity of DP is problematic, being the severity of the condition the main factor for the recommendation of a specific treatment. To improve the quality of assessment of DP and thanks to the recent emergence of novel software solutions to process point-clouds, 3D surface acquisition of the infant's head is performed. Although these strategies proved their added-value, they have high costs and require medical training to learn how to correctly manipulate the geometry acquisition system and the software. However, no 3D synthetic and realistic models are currently available, hampering the development of novel methods. In this sense, the future purpose of this work is to generate an artificial benchmark of 3D models of infant heads with deformational plagiocephaly and make it freely available to potentiate the development of these novel methods. Thus, a selection of the best parameters that characterize plagiocephaly is here performed. To create a parametric model of the head with DP, measurements retrieved from state-of-the-art studies and 40 clinical magnetic resonance images of infant heads (33 with normal shape and 7 with mild deformity) were extracted and evaluated. We expect to apply these parameters in a future work on an artificial intelligence framework to generate the models., “SmartORTHOSIS - Ortótese inteligente personalizada para plagiocefalia posicional”, with the reference NORTE-01-0145-FEDER024300, financed by the “Fundo Europeu de Desenvolvimento Regional (FEDER)”, by “Programa Operacional Regional do Norte” (NORTE2020), and by Fundação para a Ciência e Tecnologia (FCT)

Non-arteriosclerotic arteriopathies have emerged as important underlying pathomechanism in pediatric arterial ischemic stroke (AIS). The pathogenesis and classification of cerebral arteriopathies in childhood are heterogeneous. Different classifications base on (i) the anatomic site; (ii) the distribution and size of the affected vessel; (iii) the time course, for example, transient vs. progressive, monophasic vs. recurrent; (iv) the putative pathogenesis; (v) the magnetic resonance imaging morphology of the vasculopathies. Inflammation affecting the cerebral vessels is increasingly recognized as common cause of pediatric AIS. Primary cerebral vasculitis or primary angiitis of the central nervous system (CNS) in childhood (cPACNS) is an important differential diagnosis in pediatric AIS. Primary angiitis of the CNS is a rare disorder, and the pathogenesis is poorly understood so far. The current classification of cPACNS is based on the affected cerebral vessel size, the disease course, and angiographic pattern. Two large subtypes are currently recognized comprising large- and medium-sized vessel CNS vasculitis referred to as angiography-positive cPACNS and angiography-negative small vessel cPACNS. As the clinical manifestations of cPACNS are rather diverse, precise diagnosis can be challenging for the treating pediatrician because of the lack of vital laboratory tests or imaging features. Initial misdiagnosis is common because of overlapping phenotypes and pediatric AIS mimics. As untreated cPACNS is associated with a high morbidity and mortality, timely diagnosis, and induction of immunomodulatory and symptomatic therapy are essential. Survival and neurological outcome depend on early diagnosis and prompt therapy. Primary angiitis of the central nervous system in childhood differs in several aspects from primary cerebral angiitis in adults. The aim of this article is to give a brief comprehensive summary on pediatric primary cerebral vasculitis focusing on the clinical perspective regarding the classification, the putative pathogenesis, the disease course, the diagnostic tools, and emerging treatment options. A modified terminology for clinical practice is discussed.

Whole-body MRI is an imaging method that uses advanced modern MRI equipment to provide high-resolution images of the entire body. The goal of these guidelines is to specify the indications for which whole-body MRI can be recommended in children and adolescents and to describe the necessary technical requirements. CITATION FORMAT: · Schaefer JF, Berthold LD, Hahn G et al. Whole-Body MRI in Children and Adolescents - S1 Guidelines. Fortschr Röntgenstr 2019; 191: 618 - 625.Die Ganzkörper-Magnetresonanztomografie (GK-MRT) ist eine bildgebende Methode, welche unter Nutzung fortgeschrittener Verfahren moderner MRT-Geräte eine hochaufgelöste Darstellung des gesamten Körpers ermöglicht. Ziel dieser Leitlinie ist es, Indikationen zu benennen, bei denen die GK-MRT im Kindes- und Jugendalter empfohlen werden kann, und dafür notwendige, technische Voraussetzungen zu beschreiben. ZITIERWEISE: · Schaefer JF, Berthold LD, Hahn G et al. Whole-Body MRI in Children and Adolescents – S1 Guidelines. Fortschr Röntgenstr 2019; 191: 618 – 625.

Children with an unexplained bleeding tendency are frequently referred to a haemostaseologist for further evaluation. Careful standardized history taking and clinical evaluation should allow for distinguishing bleeds after minor injury and trauma which are very common in all children. However, in two groups of children bleeding symptoms may be more significant than expected: those with an underlying coagulation disorder and those who have been subjected to physical child abuse. The coexistence of child abuse and a bleeding disorder must always be considered. An extended coagulation diagnostic is required if the morphology of bleedings is not clearly suspicious for child abuse and in the absence of typical concomitant injuries, e.g., bone fractures. An interdisciplinary approach involving a forensic pathologist and a paediatric haemostaseologist for assessment of bleeding symptoms, the explanation of the clinical findings, and the critical evaluation of laboratory results are essential in such cases. This review is focussed on symptoms in accidental and nonaccidental injuries in children assisting haemostaseologists in decision making in cases of child protection issues.Kinder mit unklarer Blutungsneigung werden häufig zum Hämostaseologen zur Abklärung geschickt. Eine standardisierte Ananmneseerhebung und klinische Untersuchung erlauben es zu entscheiden, ob es sich um Blutungen durch kleine Verletzungen und Traumata handelt. In der Regel treten bei 2 Gruppen von Kindern relevante Blutungen auf: Kinder mit Gerinnungsstörung und solche, die körperlich misshandelt werden. Dabei ist stets zu berücksichtigen, dass auch gleichzeitig eine Gerinnungsstörung und eine Misshandlung vorliegen kann. Eine erweiterte Gerinnungsdiagnostik ist erforderlich, wenn die Blutungsmorphe nicht eindeutig für eine Misshandlung spricht und beim Fehlen typischer Begleitverletzungen, wie Frakturen. In diesen Fällen ist ein interdisziplinäres Vorgehen unter Einbeziehung eines Rechtsmediziners und eines pädiatrischen Hämostaseologen zur Beurteilung der Symptome, den Erklärungen für das vorliegende klinische Bild und eine kritische Bewertung der Befunde der Gerinnungsdiagnostik notwendig. Diese Übersichtsarbeit fokussiert auf Symptome bei akzidentellen und nicht-akzidentellen Verletzungen und soll eine Entscheidungshilfe für Hämostaseologen in Kinderschutzfällen darstellen.

Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disorder that most commonly affects children and adolescents. While initially considered a benign disorder, we now know that CNO is a chronic and sometimes debilitating disease. The pathophysiology of CNO is incompletely understood. Imbalanced expression of pro- and anti-inflammatory cytokines contributes to osteoclast activation and bone inflammation. Animal models support these observations and suggest the involvement of alterations to the gut microbiome in disease pathology. Currently available treatment options inhibit inflammation and/or osteoclast activity and are efficacious in a large proportion of patients. However, prospective studies are missing, and some patients develop complications before “matching” treatment has been established. Here, we discuss disease presentation and outcomes, the current understanding of disease pathology, diagnostic approaches to CNO, available treatment options, and potential future directions.

Die Fluoroskopie findet im Kindesalter zur Diagnostik von Erkrankungen der Atemwege kaum noch Anwendung. Einengungen der Nasenhaupthohlen durch Choanalstenosen und -atresien und Raumforderungen der Nase, des Pharynx und Hypopharynx konnen im Neugeborenenalter schwere Atem- und Trinkstorungen bewirken. Tracheale und bronchiale Fehlbildungen reichen vom asymptomatischen Zufallsbefund bis zum letalen Ausgang. Bei intrathorakalen Zysten kann es sich differenzialdiagnostisch um Osophagusduplikationszysten, neurenterische Zysten oder Bronchuszysten handeln. Die Osophagusatresie mit oder ohne tracheoosophagealer Fistel ist Teil eines Spektrums von Anomalien, die von der isolierten Osophagusatresie bis zur alleinigen Fistel reichen. Die Rontgendiagnostik spielt sowohl praoperativ als auch postoperativ im klinischen Alltag die wesentliche Rolle.

Das Thoraxtrauma ist zwar im Kindesalter selten, jedoch mit einer hohen Mortalitat und Morbiditat verbunden. Fremdkorperaspirationen sind die haufigsten Unfalle bei Kleinkindern im hauslichen Umfeld und konnen eine vermehrte oder verminderte Transparenz im Rontgenbild zur Folge haben. Radiologische Befunde des Asthmas bronchiale sind uberblahte Lungenareale, Bronchiektasien, Bronchialwandverdickungen und Schleimretentionen. Auch die Zystische Fibrose ist typischerweise durch diese Befunde charakterisiert; langfristig konnen irreversible Lungenparenchymdestruktionen entstehen. Die wichtigste bildgebende Methodik bei der Diagnostik einer pulmonalen Tuberkulose ist die Rontgenaufnahme. Weitere bakterielle Erreger im Kindesalter sind Streptokokken, Staphylokokken und Hamophilus influenzae. Interstitielle atypische Pneumonien sind oft bei Kindern durch RS-Viren verursacht. Chronische interstitielle Lungenerkrankungen umfassen seltene Pathologien, darunter diffuse Entwicklungsstorungen, alveolare Wachstumsstorungen und Surfactantdysfunktionen.

Historically, osteomyelitis was considered an infectious disorder. More recently, inflammatory mechanisms were recognized causing a significant proportion of pediatric osteomyelitis. This study was to compare characteristics of children with chronic non-bacterial (CNO) and bacterial osteomyelitis (BOM). A chart review of osteomyelitis patients from the departments of pediatrics, pediatric surgery, orthopedic surgery, and oral and maxillofacial surgery was conducted in a tertiary referral center, covering the years 2004–2014. Institutional incidences of CNO (n = 49) and BOM (n = 56) were comparable. Differentiation between CNO and BOM based on clinical or laboratory findings was mostly impossible. However, children with BOM more frequently presented with local inflammatory signs (47 vs. 68 %, p = 0.040), fever (12 vs. 38 %, p = 0.003), and abscesses (0 vs. 39 %, p < 0.001). Peripheral arthritis (14 vs. 0 %, p < 0.001), inflammatory bowel disease (10 vs. 2 %, p = ns), and hyperostosis (29 vs. 4 %, p = 0.001) were more common in CNO. Whole-body MRI was performed in 76 % of CNO patients, unveiling multifocal lesions in 80 % (CRMO). Though considered a rare disorder, institutional incidences of CNO were comparable to BOM, and the discrimination between CNO and BOM solely based on clinical aspects was mostly impossible. This is of special interest, since a correct and timely diagnosis is of utmost importance for long-term outcomes in both disorders. Whole-body MRIs should be considered in chronic osteomyelitis to (1) detect clinically inapparent lesions in CNO and (2) indirectly exclude (usually unifocal) chronic bacterial infections. Prospective studies are warranted to establish evidence-based diagnostic and therapeutic approaches to CNO.

Acute necrotizing encephalopathy (ANE) is a rare disease presenting with rapidly progressing encephalopathy. It usually occurs in otherwise healthy children after common viral infections. The hallmarks of ANE are the neuroradiological findings of multiple symmetric lesions in the thalami, midbrain, pons and brainstem. Most cases are sporadic and non recurrent. However, recurrent or familial forms of ANE due to mutations in RANBP2 gene have been reported. It has been suggested to give these cases the term ANE1. We report the clinical course in two male infants (P1, P2) with ANE1 and a variable clinical course and outcome. One patient is heterozygous for the most common RANBP2 missense mutation p.Thr585Met. In the other patient we observed a novel de novo missense mutation p.Trp681Cys in the RANBP2 gene causing recurrent ANE. Clinical and radiological features are presented and differential diagnoses are discussed. This report adds to the current knowledge of the phenotype in ANE, caused by mutations in RANBP2 gene.

Objectives This clinical study evaluated the pharmacokinetics (PK) and safety data of macrocyclic extracellular contrast agent gadobutrol in pediatric subjects aged younger than 2 years. Materials and methods Pediatric subjects (term newborns to those aged younger than 2 years) with normal renal function undergoing magnetic resonance imaging with gadobutrol (0.1 mmol/kg body weight [BW]) were prospectively enrolled in this open-label, multicenter clinical trial to evaluate PK as a primary end point. Plasma PK was analyzed using a population-based PK approach. Safety and qualitative efficacy (evaluation of images) were secondary end points. Safety and tolerability were assessed throughout study participation (approximately 7 days). Imaging efficacy variables were assessed by investigators. Results Forty-four subjects were evaluated for safety and efficacy; 43 subjects were eligible for PK evaluation including 9 term newborns and infants aged younger than 2 months. Gadobutrol PK in pediatric subjects aged younger than 2 years were adequately described by a linear 2-compartmental model with elimination from the central compartment. Total median systemic exposure (area under the curve) of gadobutrol was estimated at 776 μmol · h/L (range, 544-1470 μmol · h/L). Simulated median concentration at 20 minutes after injection of gadobutrol (C20) was 339 μmol/L (range, 230-456 μmol/L). Safety and tolerability profile were similar to older populations. In 1 subject (2.3%), vomiting was reported as a mild adverse event related to gadobutrol, and there were no reported serious adverse events. The evaluation of gadobutrol-enhanced images provided improved diagnosis, increased confidence in diagnosis, and contributed to subject clinical management. Conclusions The PK profile of gadobutrol in children aged younger than 2 years including newborns is similar to that in older children and adults. At the dose of 0.1 mmol/kg BW, gadobutrol had a favorable safety profile and was well tolerated with similar profile across the age range 0 to younger than 2 years and compared with older children and adults. Extrapolation of efficacy data from adults to the younger pediatric population, including term newborns, is justified. The recommended standard dose of gadobutrol (0.1 mmol/kg BW), as used in the population aged 2 years and older, is also appropriate in children aged younger than 2 years.