Wolfgang Hirsch

Pharmacokinetics and safety of gadobutrol-enhanced magnetic resonance imaging in pediatric patients.

Objectives:This clinical study investigated the pharmacokinetics and safety of gadobutrol, a magnetic resonance (MR) imaging extracellular contrast agent, in pediatric patients aged 2 to 17 years. Materials and Methods:In this open-label, multicenter study, patients scheduled for routine contrast-enhanced MR imaging of the brain, spine, liver or kidney, or MR angiography received a single intravenous injection of gadobutrol (0.1 mmol/kg/0.1 mL/kg). Patients were stratified by age groups (2–6, 7–11, and 12–17 years). Blood and urine samples were collected at prespecified time points and analyzed for gadolinium concentrations. Plasma data were evaluated by means of a nonlinear mixed effects model, and urine data were analyzed using descriptive statistics. In addition, the safety of gadobutrol was evaluated. Results:A total of 130 patients (2–6 years, n = 45; 7–11 years, n = 39; 12–17 years, n = 46) were included in the final population pharmacokinetic analysis. Gadobutrol pharmacokinetics in children aged 2 to 17 years were adequately described by an open 2-compartment model with elimination from the central compartment. The median estimates (2.5th percentile, 97.5th percentile) of body weight-normalized total body clearance (L/h/kg) per age group were 0.10 (0.05, 0.17) for all ages, 0.13 (0.09, 0.17) in the 2 to 6 year age group, 0.10 (0.05, 0.17) in the 7 to 11 year age group and 0.09 (0.05, 0.10) in the 12 to 17 year age group. The body weight-normalized median estimates of total volume of distribution (L/kg) were 0.20 (0.12, 0.28) for all ages, 0.24 (0.20, 0.28) in the 2 to 6 year age group, 0.19 (0.14, 0.23) in the 7 to 11 year age group and 0.18 (0.092, 0.23) in the 12 to 17 year age group. Median gadolinium plasma concentrations at 20 minutes postinjection were simulated using the population pharmacokinetic model and ranged from 414 (13 kg subject) to 518 &mgr;mol/L (65 kg subject). Body weight was identified as the major covariate influencing the pharmacokinetic parameters of total body clearance and central volume of distribution. Age was not found to be an additional independent parameter. The median amount of renally excreted gadolinium was 77.0% of the administered dose within 6 hours postinjection, indicating that gadobutrol was renally excreted in this pediatric population aged 2 to 17 years. Gadobutrol was well tolerated, with drug-related adverse events of mild intensity reported for 8 (5.8%) of 138 patients. Conclusions:Observed differences in pharmacokinetics were attributed to body weight, with no additional independent effect of age. Thus, no dose adjustment from the standard dose of gadobutrol in adults based on body weight (0.1 mmol/kg) is necessary in pediatric patients aged 2 to 17 years. Gadobutrol was safe and well tolerated in the pediatric population in this study.

MRI of the lungs in children.

Lung diseases of children often need diagnostic imaging beyond X-ray. Although CT is considered the gold standard of lung imaging, MRI is sufficient to answer most of the questions raised. After all, the exposure to radiation caused by one CT examination corresponds to approximately the effective dose of 200 chest radiographs. What is MRIs potential in the lung today? In diseases with alveolar pathology, cardiac- and respiratory-triggered MRI examinations are roughly equivalent to CT examinations. Distinct interstitial processes are easily diagnosable using MRI. Early interstitial processes may be missed by MRI, but conventional plain films fail to recognize them just as often. For identification of lung metastases, CT is still used as the initial diagnostic measure. Subsequent therapy monitoring may then be carried out with the help of MRI. Small bullae and pulmonary emphysema at present pose a problem to MRI. On the other hand, MRI is reliable for follow-up examinations in inflammatory diseases or for imaging of complications, and the increased use of lung MRI as an alternative to chest CT may contribute immensely to reducing radiation exposure in children.

Updated physiology and pathophysiology of CSF circulation—the pulsatile vector theory

IntroductionHydrocephalus is still a not well-understood diagnostic and a therapeutic dilemma because of the lack of sufficient and comprehensive model of cerebrospinal fluid circulation and pathological alterations.ConclusionsBased on current studies, reviews, and knowledge of cerebrospinal fluid dynamics, brain water dynamics, intracranial pressure, and cerebral perfusion physiology, a new concept is deducted that can describe normal and pathological changes of cerebrospinal fluid circulation and pathophysiology of idiopathic intracranial hypertension.

Magnetic resonance angiography in a patient with Crohn's disease associated cerebral vasculitis

Vasculitits of the central nervous system (CNS) is a known complication of chronic inflammatory bowel diseases. We report the case of a female patient with Crohns disease, developing vasculitis of the CNS with evidence of pathological vessel depiction on magnetic resonance angiography. To our knowledge this is the first case report regarding MRA documentation of vessel changes typical for angiitis in a patient with Crohn-associated vasculitis of the CNS.

Severe head trauma in children: cranial computer tomography and clinical consequences

Background: We investigated the prognostic and therapeutic implications of cranial computerized tomography (CCT) examinations after severe head trauma in children.

Contrast-Enhanced Magnetic Resonance Imaging in Pediatric Patients: Review and Recommendations for Current Practice

Magnetic resonance imaging (MRI), frequently with contrast enhancement, is the preferred imaging modality for many indications in children. Practice varies widely between centers, reflecting the rapid pace of change and the need for further research. Guide-line changes, for example on contrast-medium choice, require continued practice reappraisal. This article reviews recent developments in pediatric contrast-enhanced MRI and offers recommendations on current best practice. Nine leading pediatric radiologists from internationally recognized radiology centers convened at a consensus meeting in Bordeaux, France, to discuss applications of contrast-enhanced MRI across a range of indications in children. Review of the literature indicated that few published data provide guidance on best practice in pediatric MRI. Discussion among the experts concluded that MRI is preferred over ionizing-radiation modalities for many indications, with advantages in safety and efficacy. Awareness of age-specific adaptations in MRI technique can optimize image quality. Gadolinium-based contrast media are recommended for enhancing imaging quality. The choice of most appropriate contrast medium should be based on criteria of safety, tolerability, and efficacy, characterized in age-specific clinical trials and personal experience.

Operative management of idiopathic spinal intradural arachnoid cysts in children: a systematic review.

BackgroundSpinal intradural arachnoid cysts are rare with only a few patients reported so far. Idiopathic, traumatic, posthemorrhagic, and postinflammatory causes have been reported in the literature. Especially, idiopathic lesions, in which other possible etiological factors have been ruled out, seem to be rare.Patients and MethodsWe systematically reviewed the literature in regards to localization within the spinal canal, treatment options, complications, and outcome. Additionally, we present management strategies in two progressively symptomatic children less than 3 years of age with idiopathic intradural arachnoid cysts.ResultsIn total, 21 pediatric cases including the presented cases have been analyzed. Anterior idiopathic spinal arachnoid cysts are predominantly located in the cervical spine in 87.5 % of all cases, whereas posterior cysts can be found at thoracic and thoracolumbar segments in 84.6 % of the patients. Most children presented with motor deficits (76.2 %). Twenty-five percent of anterior spinal arachnoid cysts caused back pain as the only presenting symptom. Open fenestration by a dorsal approach has been used in the vast majority of cases. No major surgical complications have been reported. Ninety-four percent of all patients did improve or showed no neurological deficits. Recurrence rate after successful surgical treatment was low (9.5 %).ConclusionIdiopathic spinal intradural arachnoid cysts can present with neurological deficits in children. Pathologies are predominantly located in the cervical spine anteriorly and in thoracic and thoracolumbar segments posteriorly to the spinal cord. In symptomatic cases, microsurgical excision and cyst wall fenestration via laminotomy are recommended. Our radiological, intraoperative, and pathological findings support the cerebrospinal fluid obstruction and vent mechanism theory of arachnoid cysts.

www.PedRad.info, the first bilingual case-oriented publication platform for pediatric radiology

On the Internet, there are few pediatric radiology databases. The most important and complete Web site is PediatricRadiology.com, which provides many radiological links but does not have its own database. We present an Internet project called PedRad.info (also known as Kinderradiologie-Online). The open-source, case-oriented publication platform publishes validated pediatric radiology findings on the Internet. A comparable on-line program, even for adult radiology, does not exist, so this tool is a pioneer in the area of Web-based information technology for medical and radiological communities.

A Rare Case of Congenital Choroid Plexus Carcinoma

We report a 1-year-old child with the prenatal (week 29 + 5) diagnosis of a brain tumor. The parents were informed about all aspects of prognosis and options concerning termination of pregnancy. The parents opted for an aggressive therapeutic approach after extensive and informative case conferences and counseling. The histopathological diagnosis after partial tumor resection was choroid plexus carcinoma, two weeks thereafter tumor size was progressive. The parents opted for palliative treatment at this stage. The patient died at the age of one year. Ethical aspects have to be actively considered and addressed when caring for children with choroid plexus carcinoma.

Tetrasomie 18p@@@Tetrasomy 18p: 2-jähriges Mädchen mit einer psychomotorischen Entwicklungsretardierung, Spastik der unteren Extremität und kleineren Dysmorphiezeichen@@@A 2-year-old girl with retarded psychomotoric development, spasticity of the lower extremities and minor dysmorphic features

ZusammenfassungDie Tetrasomie 18p ist eine seltene numerische Chromosomenstörungen. Der Phänotyp resultiert aus dem Vorliegen eines kleinen überzähligen metazentrischen Markerchromosoms, eines Isochromosom 18p. Zu den typischen Merkmalen dieses chromosomalen Syndroms gehören Kleinwuchs, Mikrozephalie, mentale Retardierung sowie eine spastische Bewegungsstörung besonders der unteren Extremität. Wir berichten von einem 2-jährigen Mädchen, das aufgrund einer unklaren Entwicklungsstörung zur Vorstellung kam. Die klinisch-genetische Untersuchung ergab eine komplexe Entwicklungsstörung mit mild ausgeprägten Dysmorphiezeichen. Zur Abklärung führten wir eine Chromsomenanalyse mittels GTG-Bänderung durch. Diese ergab das Vorliegen eines zusätzlichen Markerchromosoms. Durch weitere Untersuchungen mittels Spectral Karyotyping (SKY™) und Fluoreszenz-in-situ-Hybridisierung (FISH) konnte das Chromosomenfragment als Isochromosom 18p identifiziert werden.AbstractTetrasomy 18p is a rare chromosomal disorder. The phenotype results from the presence of a small extra metacentric marker chromosome, an isochromosome 18p. The syndrome is characterized by mild to moderate mental retardation, microcephaly, minor dysmorphic features and spasticity of the lower limbs. Here we report on a 2-year-old girl, who was referred because of developmental delay and minor dysmorphic signs. Cytogenetic investigations revealed a small supernumerary marker chromosome. Further analysis using spectral karyotyping (SKY™) and fluorescence in situ hybridization (FISH) identified the marker chromosome fragment as an isochromosome 18p.