Sascha Meyer

Multifocal Signal Loss at Bridging Veins on Susceptibility-Weighted Imaging in Abusive Head Trauma

Identifying abusive head trauma (AHT) in infants is difficult because often there are no externally visible injuries and symptoms are nonspecific. The radiological finding that usually raises suspicion of AHT—especially when found with retinal hemorrhage and inappropriate history—is subdural hematoma (SDH). In addition to that, bridging vein thrombosis, assessed by imaging or autopsy, has been reported as a sign of the traumatic cause of SDH. Here we present two cases of AHT-associated SDH in infants, in which multifocal signal loss at bridging veins was present on susceptibility-weighted imaging without signs of venous infarction. As susceptibility-weighted imaging has been reported to be more sensitive for blood products than gradient-echo T2-weighted imaging, we propose that it might help to identify clot formation on injured bridging veins and therefore increase the sensitivity of imaging studies for a traumatic cause of SDH, helping to identify AHT that is considered to be caused by violent shaking.

Topical Rapamycin for Facial Angiofibromas in a Child with Tuberous Sclerosis Complex (TSC): A Case Report and Long-Term Follow-up

Tuberous sclerosis complex (TSC) is a genetic multisystem disorder with prominent skin involvement including facial angiofibromas that often appear in early childhood. Here we report the case of a 12-year-old girl with widespread disfiguring facial angiofibromas that were successfully treated with topical rapamycin, a mTOR inhibitor. A sustained remission of skin lesions was documented in detail over a 3-year follow-up. This case highlights the fact that topical rapamycin is a useful option in treating TSC-associated skin lesions. Especially in medically complex patients topical treatment may lessen the need for surgical interventions, reducing the risks of surgery, its adverse effects and permanent scarring. However, there is no standard dose or formulation at present. Topical rapamycin appears safe, but long-term maintenance therapy is necessary to prevent facial lesions from regrowth.

Dermatological manifestations of tuberous sclerosis complex (TSC)

Tuberous sclerosis complex (TSC) is a genetic multisystem disorder with prominent skin involvement that frequently occurs in early childhood. Dermatologic manifestations include facial angiofibromas, hypomelanotic macules, fibrous cephalic plaques, shagreen patches, and ungual fibromas. The International TSC Consensus Conference in 2012 provided guidelines for standardized baseline evaluation and follow‐up. Detailed clinical dermatological evaluation at the time of diagnosis and annual skin examination is recommended for both pediatric and adult populations. The onset of dermatological manifestations is clearly age‐related. However, dermatologists also have to assess for clinical manifestations beyond their own specialty. With advances in genetics and the advent of mTORC1 inhibitors, new specific therapeutic options have become available for TSC patients with skin manifestations. Early intervention is commonly recommended for symptomatic, rapidly evolving, disfiguring, or debilitating lesions. The consensus guidelines recommend “treatment as appropriate for the lesion and clinical context” and suggest the use of surgical excision, laser therapy, or topical mTORC1 inhibitors. Topical mTORC1 inhibitors present a useful option for TSC‐associated skin lesions, particularly in medically complex patients. They may prevent or reduce the risks of subsequent surgeries and permanent scarring.

Ante-, peri- and postnatal factors associated with intraventricular hemorrhage in very premature infants

BACKGROUNDnIntraventricular hemorrhage (IVH) is one of the most serious complications in preterm infants and is associated with neurological sequelae and mortality. Over the past few decades, the rate of IVH has decreased due to improved neonatal intensive care. However, up to 15-25% of very and extremely premature infants (<32 and <28weeks of pregnancy (WOP) respectively) still suffer from IVH.nnnSTUDY PURPOSEnThe aim of this study was to perform an updated, multicenter analysis to identify ante-, peri, and postnatal factors other than gestational age/birth weight associated with IVH of any grade in a large cohort of very and extremely premature infants.nnnMETHODSnWe performed a retrospective analysis in a prospectively conducted multicenter cohort study between 01/01/1998-31/12/2012 at 5 level 3 perinatal centers. All relevant ante-, peri- and neonatal data were collected and univariate as well as multivariate logistic regression analysis was performed.nnnRESULTSn765 inborn infants with a gestational age<32 WOP were enrolled into this study (369 (48.2%) female; 396 (51.8%) male). Birth weight ranged from 315g to 2200g (mean 1149.7g, SD 371.9g); 279 (36.5%) were born ≤27+6 WOP and 486 (63.5%)≥28+0 WOP. IVH was seen in 177 (23.1%) patients. Multivariate analysis revealed that in addition to higher gestational age (OR 0.7, CI [0.6-0.8]), antenatal steroid treatment (OR 0.3, CI [0.2-0.6]) and caesarian section without uterine contraction (OR 0.6, CI [0.4-0.9]) were associated with a lower rate of IVH while RDS (OR 5.6, CI [1.3-24.2]), pneumothorax (OR 2.8, CI [1.4-5.5]) and use of catecholamines (OR 2.7, CI [1.7-4.5]) were associated with an increased risk of IVH. After exclusion of gestational age and birth weight from multivariate analysis, early onset sepsis (OR 1.6, CI [1.01-2.7]) and patent ductus arteriosus (OR 1.9, CI [1.1-3.1]) were associated with a higher rate of IVH. In addition, univariate analysis revealed that Apgar scores at 5min (p<0.001), BDP/ROP/NEC (p<0.001), mechanical ventilation (p<0.001) and inhalative nitric oxide (p<0.001) were significantly associated with IVH.nnnCONCLUSIONSnOur comprehensive analysis demonstrated that the occurrence of IVH in very premature infants is significantly associated with ante-, peri- and postnatal factors being either related to the degree of immaturity or indicating a critical clinical course after birth. The analysis reiterates the necessity for a very close cooperation between obstetricians and neonatologists to reduce the incidence of IVH in this susceptible cohort.

Preterm Birth Affects the Risk of Developing Immune-Mediated Diseases

Prematurity affects approximately 10% of all children, resulting in drastically altered antigen exposure due to premature confrontation with microbes, nutritional antigens, and other environmental factors. During the last trimester of pregnancy, the fetal immune system adapts to tolerate maternal and self-antigens, while also preparing for postnatal immune defense by acquiring passive immunity from the mother. Since the perinatal period is regarded as the most important “window of opportunity” for imprinting metabolism and immunity, preterm birth may have long-term consequences for the development of immune-mediated diseases. Intriguingly, preterm neonates appear to develop bronchial asthma more frequently, but atopic dermatitis less frequently in comparison to term neonates. The longitudinal study of preterm neonates could offer important insights into the process of imprinting for immune-mediated diseases. On the one hand, preterm birth may interrupt influences of the intrauterine environment on the fetus that increase or decrease the risk of later immune disease (e.g., maternal antibodies and placenta-derived factors), whereas on the other hand, it may lead to the premature exposure to protective or harmful extrauterine factors such as microbiota and nutritional antigen. Solving this puzzle may help unravel new preventive and therapeutic approaches for immune diseases.

Tuberöse Sklerose@@@Tuberous sclerosis complex

ZusammenfassungDie tuberöse Sklerose ist eine autosomal-dominante Erkrankung mit unterschiedlich ausgeprägter Beteiligung des zentralen Nervensystems (ZNS) und vieler anderer Organsysteme. Zu ihren radiologischen Merkmalen gehören verschiedene Veränderungen des ZNS, der Lunge, der Nieren und des Herzens. Die Bildgebung ist wichtig für die Früherkennung von Komplikationen. Dieser Artikel dient der Übersicht über das klinische Bild, die Therapie sowie die spezifische Bildgebung der tuberösen Sklerose.AbstractTuberous sclerosis complex is an autosomal dominant disorder with variable affection of the central nervous system (CNS) and many other organ systems. Radiological features include various lesions of the brain as well as lesions of the lungs, kidneys and the heart. Imaging is important for the early detection of complications. This article provides an overview of the clinical features and therapy as well as the specific imaging of tuberous sclerosis complex.Tuberous sclerosis complex is an autosomal dominant disorder with variable affection of the central nervous system (CNS) and many other organ systems. Radiological features include various lesions of the brain as well as lesions of the lungs, kidneys and the heart. Imaging is important for the early detection of complications. This article provides an overview of the clinical features and therapy as well as the specific imaging of tuberous sclerosis complex.

Association of Chiari malformation and vitamin B12 deficit in a family

PurposeA clear etiology of Chiari malformation is still lacking. Some associations between this disorder and genetical variations have been reported. Documented cases of familial Chiari malformation in three consecutive generations are rare. Furthermore, an association of Chiari disorder and vitamin B12 deficit has rarely been described in literature.MethodsIn this study, three generations of a family suffering from Chiari 1 or Chiari 0 malformation have been examined with MRI, clinically and laboratory (hemograms).ResultsChiari malformation could be confirmed in all presented patients: While the F2 generation (children: 1u2009×u2009♀, 1u2009×u2009♂) and the female F1 generation (mother and sister of mother) suffered from Chiari type 1, the male F0 generation showed Chiari 0 malformation. F0 and F1 generation further presented with syringomyelia (F0: C4-D1; F1: C4-D2). All patients except the grandfather (F0) underwent surgical posterior fossa decompression to relive successfully cerebellar and hydrocephalus associated progressing clinical symptoms. The hemograms of generation 1 and 2 revealed familial vitamin B12 deficit.ConclusionsA hereditary component is discussed in Chiari malformation, yet proved etiology is still lacking. As folic acid plays an important role in the development of the neural tube, vitamin B12 deficit might have some impact on the development of Chiari malformations.

Optimized care in Patients with Rare Diseases: TSC at the Center for Rare Diseases (ZSEUKS) at Saarland University Medical Center, Germany

Providing comprehensive medical care for patients with rare diseases is both challenging and rewarding. We will give a short summary of the most relevant medical issues pertinent to this subject, and will illustrate some of these issues by sharing our experience in the care of patients with TSC disease.

Reference values for nucleated red blood cells and serum lactate in very and extremely low birth weight infants in the first week of life

STUDY PURPOSEnTo provide reference values for nucleated red blood cells and serum lactate concentrations in very and extremely low birth weight (VLBW/ELBW) infants in the first week of life.nnnPATIENTS AND METHODSnRetrospective data analysis of serial, daily measurements of NRBC counts and serum lactate during the first 6days of life in VLBW and ELBW infants.nnnRESULTSnIn total, 250 infants<1500g were included in this study. Intrauterine growth retardation (IUGR) was seen in 87 (34.8%) patients. Gestational age (GA) ranged from 23 to 35weeks (mean 29.0weeks) and birth weight (BW) was 320-1499g (mean 1047.9g). During hospital stay, 55 (22%) patients developed IVH and 55 children (22%) BPD. PVL was seen in 12 (4.8%) cases, ROP in 93 (37.2%) and NEC in only 1 (0.4%) patient. NRBC counts as well as serum lactate concentrations depended significantly on birth weight (p<0.01) and presence respectively absence of IUGR (p<0.01). Both NRBC counts and serum lactate concentrations declined constantly during the 6-day period (p<0.01), and both were highly inter-correlated (p<0.01).nnnCONCLUSIONSnThis is one of only a very few studies that systematically and serially evaluated both NRBC counts and serum lactate concentration in VLBW and ELBW infants in the first 6days of life. Both parameters were significantly dependent on birth weight and the presence of IUGR. Moreover, a significant correlation between NRBC counts and serum lactate concentrations in this early period of life could be demonstrated. In future studies, the role of these readily available biomarkers in predicting important neonatal outcome parameters needs to be evaluated in a prospective manner.

The role and limitations of Cochrane reviews at the bedside: a systematic synopsis of five pediatric subspecialties

SummaryBackgroundCochrane meta-analyses provide the physician at the bedside with the most relevant, up-to-date clinical information. However, implementation of evidence-based medicine (EBM) at the bedside may be difficult for axa0variety of reasons. The aim of this study was to assess relevant issues and obstacles related to implementing EBM in pediatrics in real life at the bedside/cotside.MethodsWe performed five systematic literature reviews of all published Cochrane reviews in neonatology (1996–2010), pediatric neurology (1996–2010), pediatric gastroenterology (1993–2012), pediatric cardiology (2001–2015), and complementary and alternative medicine (1996–2012; CAM) in children and neonates. In all five analyses, the main outcome variables were percentage of reviews concluding that axa0certain intervention provides axa0benefit, percentage of reviews concluding that axa0certain intervention should not be performed, and percentage of studies concluding that the current level of evidence is inconclusive.ResultsIn all five areas of pediatrics, axa0substantial number of Cochrane reviews yielded inconclusive data (neonatology: 46.6%; neuropediatrics: 26.8%; pediatric gastroenterology: 27.9%; pediatric cardiology: 42.9%; complementary and alternative medicine: 66.9%).ConclusionsOur up-dated systematic synopsis reiterates the need for high-quality, sophisticated research to reduce the number of inconclusive meta-analyses in the field of pediatrics—most importantly in the field of complementary and alternative medicine (CAM), neonatology, and pediatric cardiology. The realization of high-quality, clinically driven research will in turn yield more systematic reviews with axa0clear conclusion (e.u2009g., in favor or against axa0certain intervention, or treatment modality), thus, substantively decreasing the proportion of inconclusive reviews.