Relapse of a group 4 medulloblastoma after 18 years as proven by histology and DNA methylation profiling.

BACKGROUND: Recent studies on medulloblastomas (MB) suggest that a large fraction of tumors appearing as late recurrence turn out to be secondary malignancies, e.g., malignant gliomas, after thorough molecular investigation. RESULTS: Here, we report of a patient with a group 4 MB that developed a distant recurrence after more than 18 years. The recurrent tumor was confirmed by histology and genome-wide DNA methylation profiling. CONCLUSION: Our case not only illustrates the potential of very late recurrences after seemingly cured group 4 MB, but also illustrates that detailed molecular analyses are indispensable in patients with a history of a previous malignancy.

Predictive factors associated with ventriculoperitoneal shunting after posterior fossa tumor surgery in children.

PURPOSE: The aim of the study was to evaluate established risk factors and define new inflammation-associated factors associated with postoperative ventriculoperitoneal shunt placement. METHODS: The electronic medical records of children who underwent surgery for a tumor in the posterior fossa between January 2009 and January 2018 were retrospectively analyzed. Factors evaluated include age, clinical symptoms, tumor type, extent of surgical tumor resection, treatment with EVD and/or ETV, radiological findings, postoperative serum CRP, and leucocyte levels. Tumor tissue was stained immunohistochemically with antibodies against CD3, and leucocyte counts were performed. Patients with pre- or postoperative signs of infection or confirmation of a concurrent infection were excluded from some analyses. RESULTS: Seventy patients ages 0.4-20.8 years (median, 8.2) were included. Forty-five of 70 (65.3%) presented postoperative radiological signs of hydrocephalus. Fifteen of 70 (21.4%) patients required shunt placement postoperatively. Shunt placement was significantly associated with age < 3 years at diagnosis (p = 0.013), perioperative EVD placement (p < 0.001), signs of hydrocephalus in postoperative imaging (p = 0.047), a frontooccipital horn ratio (FOHR) > 0.46 within the first 72 h postoperatively (p < 0.001), and the presence of intraventricular blood postoperatively (p = 0.007). Six patients who underwent shunting had serum CRP levels > 40 mg/l (p = 0.030) within the first 48 h postoperatively. Tumor type or extent of resection did not correlate with shunt placement. CONCLUSIONS: Several established and new factors associated with shunt placement after posterior fossa tumor surgery could be identified. Additional studies are needed to explore the aseptic inflammation pathways involved with increased CRP levels and shunt placement.

Tectal gliomas: assessment of malignant progression, clinical management, and quality of life in a supposedly benign neoplasm.

OBJECTIVE Tectal gliomas constitute a rare and inhomogeneous group of lesions with an uncertain clinical course. Because these supposedly benign tumors are frequently followed up by observation over many years, the authors undertook this analysis of their own case series in an effort to demonstrate that the clinical course is highly variable and that there is a potential for a progressive biology. METHODS Clinical data analysis of 23 cases of tectal glioma (involving 9 children and 14 adults) was performed retrospectively. Radiographic data were analyzed longitudinally and MR images were evaluated for tumor volume, contrast enhancement, and growth progression. Quality of life was assessed using the EORTC BN20 and C30 questionnaires during follow-up in a subgroup of patients. RESULTS The patients' mean age at diagnosis was 29.2 years. The main presenting symptom at diagnosis was hydrocephalus (80%). Six patients were treated by primary tumor resection (26.1%), 3 patients underwent biopsy followed by resection (13.1%), and 3 patients underwent biopsy only (13.1%). For additional treatment of hydrocephalus, 14 patients (60.9%) received shunts and/or endoscopic third ventriculostomy. Radiographic tumor progression was observed in 47.9% of the 23 cases. The mean time between diagnosis and growth progression was 51.5 months, and the mean time to contrast enhancement was 69.7 months. Histopathological analysis was obtained in 12 cases (52.2%), resulting in 5 cases of high-grade glioma (3 cases of glioblastoma multiforme [GBM], grade IV, and 2 of anaplastic astrocytoma, grade III), 5 cases of pilocytic astrocytoma, 1 diffuse astrocytoma, and 1 ganglioglioma. Malignant progression was observed in 2 cases, with 1 case progressing from a diffuse astrocytoma (grade II) to a GBM (grade IV) within a period of 13 years. Quality-of-life measurements demonstrated distinct functional deficits compared to a healthy sample as well as glioma control cohorts. CONCLUSIONS Analysis of this case series shows that a major subpopulation of tectal gliomas show progression and malignant transformation in children as well as in adolescents. These tumors therefore cannot be considered inert lesions and require histological confirmation and close follow-up. Quality-of-life questionnaires show that tectal glioma patients might benefit from special psychological support in emotional, social, and cognitive functionality.

Maternal Aneurysmal Subarachnoid Hemorrhage During Pregnancy as an Interdisciplinary Task.

Maternal aneurysmal subarachnoid hemorrhage (aSAH) during pregnancy presents a challenge regarding treatment and management. Due to the limited number of cases there are no treatment guidelines available. Thus, treatment is usually done on a case-by-case basis. Here we report on four cases of aSAH during pregnancy, describing the different management strategies and suggesting a possible treatment algorithm. Patients treated between 2003 and 2013 in our center were included in this retrospective study. Clinical data focused on time management concerning gestation week (GW), microsurgical or endovascular treatment, and outcome of the patients and the fetuses. Results were compared to the present literature on this issue. Mean age was 30.8 years, initial Hunt & Hess (H&H) grade ranged from III to V. All patients suffered from aSAH during the 3rd trimester of pregnancy. In the four cases, two emergency Caesarean sections (CS) were performed. Two aneurysms were occluded by microsurgical clipping and one was treated endovascularly. One patient died before definitive treatment of the aneurysm could be achieved, whereas fetal mortality was 0%. The mean follow-up was 83 months. aSAH during pregnancy needs individualized interdisciplinary management. Efforts must focus on the mother so that a delay in the best available treatment for the pregnant patient is avoided. Therefore treatment modality should be primarily determined by the aneurysm itself. However, timing in terms of delivery of the fetus and aneurysm treatment is a crucial point.

A Comparison between Pediatric and Adult Patients after Cranioplasty: Aseptic Bone Resorption Causes Earlier Revision in Children.

BACKGROUND AND STUDY AIMS/OBJECTIVE: Cranioplasty, a common neurosurgical intervention following decompressive craniectomy (DC), is associated with high complication rates. Bone flap resorption in particular leads to a considerable number of patients requiring further surgery. The aim of this study was to investigate the frequency and time of occurrence of complications following cranioplastic procedures in children and adults. MATERIAL AND METHODS: Data of children and adults who underwent cranioplasty between July 2010 and March 2018 were analyzed retrospectively. Clinical data, complications, and risk factors regarding aseptic bone resorption (ABR) were evaluated including patient age, occurrence of shunt-dependent hydrocephalus, and number of fragments in autologous bone flaps. RESULTS: Severe traumatic brain injury (TBI) was the leading cause for DC among children (66.7%), associated with a significantly higher number of fragments (p = 0.002). In the adult population, the most common cause was malignant infarction (55.9%) followed by TBI (24.6%). Pediatric patients in our institution received autologous bone flaps less frequently than adult patients (61.1% and 83.1%, respectively). Young age and a higher number of fragments in autologous bone flaps were associated with the occurrence of ABR. Children and adolescents showed significantly higher rates of aseptic bone necrosis (p = 0.007) and revision cranioplasty (p = 0.036). Kaplan-Meier estimates were used to further analyze bone flap resorption in children and adults, showing that revision surgery due to ABR was performed earlier in children (p = 0.001, log-rank test). CONCLUSION: Pediatric patients demand specific care when cranioplasty is performed following DC. We identified age as an independent risk factor. The higher number of fragments appears to be a correlation due to the higher number of TBIs in children. Our data indicate that young age is the most important risk factor for the development of ABR as a frequent and early complication with a shorter revision-free time interval in children. Consequently, the uncritical use of cryopreserved autologous bone flaps should be questioned in this population.

Observed versus expected mortality in pediatric patients intubated in the field with Glasgow Coma Scale scores < 9.

PURPOSE: A Glasgow Coma Scale (GCS) score of 8 or less in patients suffering from severe traumatic brain injury (TBI) represents a decision-making marker in terms of intubation. This study evaluated the impact of prehospital intubation on the mortality of these TBI cases among different age groups. METHODS: This study included the data from patients predominantly suffering from severe TBI [Abbreviated Injury Scale (AIS) of the head ≥ 3, GCS score < 9, Injury Severity Score (ISS) > 9] who were registered in TraumaRegister DGU® from 2002 to 2013. An age-related analysis of five subgroups was performed (1-6, 7-15, 16-55, 56-79, and ≥ 80 years old). The observed and expected mortality were matched according to the Revised Injury Severity Classification, version II. RESULTS: A total of 21,242 patients were included. More often, the intubated patients were severely injured when compared to the non-intubated patients (median ISS 29, IQR 22-41 vs. 24, IQR 16-29, respectively), with an associated higher mortality (42.2% vs. 30.0%, respectively). When compared to the calculated expected mortality, the observed mortality was significantly higher among the intubated patients within the youngest subgroup (42.2% vs. 33.4%, respectively; p = 0.03). CONCLUSIONS: The observed mortality in the intubated children 1-6 years old suffering from severe TBI seemed to be higher than expected. Whether or not a GCS score of 8 or less is the only reliable criterion for intubation in this age group should be investigated in further trials.

Sport-Related Traumatic Brain Injury with and without Helmets in Children.

BACKGROUND: Soccer, bicycling, and horseback riding are sports most commonly associated with traumatic brain injury (TBI) in Germany. The latter 2 sports activities are commonly practiced with helmets, and data on helmet use and usefulness vary widely. METHODS: On Ethics Committee approval, a retrospective analysis was performed for patients age 5-17 between January 2009 and August 2014 based on a diagnosis of TBI, using the electronic patient file for 2 university hospital locations. Descriptive data analysis and multivariate and univariate logistic regression were used to calculate odds ratios (ORs). RESULTS: A total of 380 children were identified, including 162 females (42.6%) and 218 males (57.4%), with a mean age of 11.9 ± 3.8 years. Activities included bicycling (n = 64), horseback riding (n = 19), and soccer (n = 16). Helmet use was documented in 26 patients (14 cyclists, 12 riders), and nonuse was documented in 20 (all cyclists). Compared with not wearing a helmet, wearing a helmet was associated with a trend toward lower odds of loss of consciousness (OR, 0.7; 95% confidence interval [CI], 0.18-2.52). A cohort of 251 patients with non-sports-related TBI (NSTBI) served as a control group for further analyses. Compared with the NSTBI group, the odds of amnesia were 2.9 times greater (95% CI, 1.1-21.6) in the patients with a riding-related TBI and 4.8 times greater (95% CI, 0.3-239) in those with a cycling-related TBI, and the odds of epidural hematoma were 2.2 times greater (95% CI, 0.4-12.3) in those with a cycling-related TBI and 4.9 times greater (95% CI, 0.5-50.4) greater in those with a soccer-related TBI. CONCLUSIONS: We gained important epidemiologic data on pediatric TBI in our region. Despite the descriptive nature of the data, a trend toward reduced odds of loss of consciousness was seen in the helmet wearers. Nevertheless, serious injury can occur despite helmet use.

Impact of Glasgow Coma Scale score and pupil parameters on mortality rate and outcome in pediatric and adult severe traumatic brain injury: a retrospective, multicenter cohort study.

OBJECTIVE Prediction of death and functional outcome is essential for determining treatment strategies and allocation of resources for patients with severe traumatic brain injury (TBI). The aim of this study was to evaluate, by using pupillary status and Glasgow Coma Scale (GCS) score, if patients with severe TBI who are ≤ 15 years old have a lower mortality rate and better outcome than adults with severe TBI. METHODS A retrospective cohort analysis of patients suffering from severe TBI registered in the Trauma Registry of the German Society for Trauma Surgery between 2002 and 2013 was undertaken. Severe TBI was defined as an Abbreviated Injury Scale of the head (AIShead) score of ≥ 3 and an AIS score for any other part of the body that does not exceed the AIShead score. Only patients with complete data (GCS score, age, and pupil parameters) were included. To assess the impact of GCS score and pupil parameters, the authors also used the recently introduced Eppendorf-Cologne Scale and divided the study population into 2 groups: children (0-15 years old) and adults (16-55 years old). Each patient's outcome was measured at discharge from the trauma center by using the Glasgow Outcome Scale. RESULTS A total of 9959 patients fulfilled the study inclusion criteria; 888 (8.9%) patients were ≤ 15 years old (median 10 years). The overall mortality rate and the mortality rate for patients with a GCS of 3 and bilaterally fixed and dilated pupils (19.9% and 16.3%, respectively) were higher for the adults than for the pediatric patients (85% vs 80.9%, respectively), although cardiopulmonary resuscitation rates were significantly higher in the pediatric patients (5.6% vs 8.8%, respectively). In the multivariate logistic regression analysis, no motor response (OR 3.490, 95% CI 2.240-5.435) and fixed pupils (OR 4.197, 95% CI 3.271-5.386) and bilateral dilated pupils (OR 2.848, 95% CI 2.282-3.556) were associated with a higher mortality rate. Patients ≤ 15 years old had a statistically lower mortality rate (OR 0.536, 95% CI 0.421-0.814; p = 0.001). The rate of good functional outcomes (Glasgow Outcome Scale Score 4 or 5) was higher in pediatric patients than in the adults (72.2% vs 63.1%, respectively). CONCLUSIONS This study found that severe TBI in children aged ≤ 15 years is associated with a lower mortality rate and superior functional outcome than in adults. Also, children admitted with a missing motor response or fixed and bilaterally dilated pupils also have a lower mortality rate and higher functional outcome than adults with the same initial presentation. Therefore, patients suffering from severe TBI, especially pediatric patients, could benefit from early and aggressive treatment.

Syringomyelia regression after shunting of a trapped fourth ventricle.

We describe a case of progressive syringomyelia following post-infectious trapped fourth ventricle (TFV), which resolved after shunting of the fourth ventricle. A 28-year-old female who had previously undergone treatment of intracerebral hemorrhage and meningitis developed a hydrocephalus with TFV. After 3 years she developed disturbance of walking and coordination. Cranial-CT revealed an enlargement of the shunted fourth ventricle as a result of shunt dysfunction. Furthermore a cervical syringomyelia developed. The patient underwent a revision of a failed fourth ventriculo-peritoneal shunt. Postoperatively, syringomyelia resolved within 6 months and the associated neurological deficits improved significantly. An insufficiency of cerebrospinal fluid draining among patients with TFV can be associated with communicating syringomyelia. An early detection and treatment seems important on resolving syringomyelia and avoiding permanent neurological deficits. Ventriculo-peritoneal shunt in trapped fourth ventricles can resolve a secondary syringomyelia.

In vitro blockade of adhesion of breast cancer cells to endothelial cells using anti-inflammatory drugs.

BACKGROUND: Increasing evidence suggests that a pro-inflammatory microenvironment affects distant metastasis of breast cancer cells, in particular by favoring tumor cell adhesion to endothelium. The aim of this study was to investigate the potential of different anti-inflammatory drugs to inhibit this effect in vitro. MATERIALS AND METHODS: Breast cancer cells from the metastatic cell line KM22 were incubated with activated Human umbilical vein endothelial cells (HUVECs). Tumor cell adhesion was quantified by fluorescence microscopy. The anti-inflammatory drugs ibuprofen, aspirin (acetylsalicylic acid), diclofenac, and dexamethasone were used as inhibiting agents. RESULTS: Aspirin and dexamethasone significantly reduced breast cancer cell adhesion to HUVECs (20.3%, p<0.000; and 25%, p<0.05, respectively). Ibuprofen and diclofenac did not significantly reduce tumor cell adhesion. CONCLUSION: Aspirin and dexamethasone seem to be able to partly inhibit adhesion of breast cancer cells to endothelium. Future studies should attempt to optimize this effect in vitro, in preparation for potential in vivo trials.