Prenatal diagnosis of meningomyelocele resolves as a mature cystic teratoma in the thoracolumbar region.

A mature cystic teratoma is a mass with heterogeneous appearance, consisting of adult tissue with two or three layers: endoderm, mesoderm, and ectoderm. It is a rare, benign transformation of somatic tissue most commonly found in the sacrococcygeal region and may resemble an uncomplicated spina bifida on prenatal ultrasonography. In this case report, we describe a female newborn with an extremely rare mature cystic teratoma in the thoracolumbar region. She presented prenatally with a preliminary diagnosis of meningomyelocele, diastematomyelia, and Chiari II malformation and a possible teratoma. However, a mass containing solid glandular tissues and bony calcifications approximately 3 × 4 cm in size was observed in the thoracolumbar region upon birth. During surgical resection, no nerve roots were found in the associated meningocele. The patient retained full lower body function postoperatively following surgical excision of the thecal sac and teratoma.

Giant cell reparative granuloma of the pediatric cranium: case report and review of the literature.

PURPOSE: Giant cell reparative granulomas are rare bone tumors. Although benign, these tumors are locally destructive and can be highly vascular. They seldom occur in the cranial vault. We describe a multidisciplinary approach to a case of giant cell reparative granuloma of the cranium in a 3-year-old patient. CASE REPORT: A 3-year-old girl female referred to the pediatric neurosurgery department for evaluation of a retro-auricular mass. She had a history of recurrent otitis media with two subsequent courses of antibiotics without resolution. CT imaging revealed an expansive lesion located in the right mastoid region. Open surgical biopsy revealed a hemorrhagic tumor consistent with a giant cell reparative granuloma. Angiography identified a hypervascular tumor blush that was supplied by the occipital artery. Preoperative transcatheter embolization was performed followed by a multidisciplinary surgical resection and reconstruction. Blood loss was minimal, and the patient recovered well after surgery. CONCLUSION: Preoperative endovascular embolization and a multidisciplinary intraoperative approach with primary resection and cranial vault reconstruction is an effective approach to hypervascular giant cell reparative granulomas.

Desmoplastic fibroma of the pediatric cranium: case report and review of the literature.

PURPOSE: Desmoplastic fibromas are primary bone tumors that seldom occur in the cranial bones. Furthermore, reports of desmoplastic fibromas of the skull in children are exceedingly rare. Although desmoplastic fibromas are histologically benign, they are locally aggressive and have a propensity to reoccur. Their radiographic appearance may mimic other more common central nervous system and bone neoplasms. There are only 19 reported cases of desmoplastic fibroma of the cranium in the literature, and only seven occurred in the pediatric age group. We present a case report of an 11-year-old female patient with a desmoplastic fibroma of the parieto-occipital region and review the literature. CASE REPORT: An 11-year-old female presented to the craniofacial clinic complaining of intermittent pain and a soft mass in the occipital region. There was a distant history of trauma to the region that did not require medical intervention. Computed tomography imaging revealed a lytic bone lesion overlying the sagittal sinus in the parieto-occipital region. Surgical resection with wide margins and immediate autologous reconstruction was performed. Pathological analysis revealed a desmoplastic fibroma. At 4 months of follow-up, no recurrence has been noted. CONCLUSION: Desmoplastic fibroma of the cranium is rare. Complete surgical resection with careful follow-up is the treatment of choice.

Intradiploic dermoid cyst of the lateral frontotemporal skull: case report and review of the literature.

BACKGROUND: Intradiploic dermoid cysts represent 0.04-0.7% of cranial tumors. Fewer than 20 cases of dermoid cysts occurring in the lateral frontotemporal region with a sinus tract and bony involvement are described, only 7 with intracranial extension. We present the first report of such a lesion arising within the lateral coronal suture. As the literature on this topic grows, the matter of preoperative imaging for soft tissue and bony lesions of the lateral frontotemporal region is evolving, and this report offers a preliminary set of criteria for when imaging is a necessity. CASE REPORT: A 2-year-old male presented with a bony lesion in the right frontotemporal region. Since birth the lesion had grown commensurately with the patient. Examination revealed an immobile hard mass overlying the right coronal suture with no discernable abnormality. Computed tomography demonstrated a cystic lesion without evidence of intracranial extension. Intraoperatively, the exophytic lesion was fully enclosed by bony matrix, interrupting the coronal suture as it approached the pterion. Following resection, pathology revealed an intradiploic dermoid cyst. CONCLUSION: Intradiploic dermoid cysts occurring within patent cranial sutures away from the midline are rarely described lesions. Complete surgical resection with careful follow-up is the treatment of choice.

A serotype 5/3 adenovirus expressing MDA-7/IL-24 infects renal carcinoma cells and promotes toxicity of agents that increase ROS and ceramide levels.

Agents that generate reactive oxygen species (ROS) are recognized to enhance MDA-7/IL-24 lethality. The present studies focused on clarifying how such agents enhanced MDA-7/IL-24 toxicity in renal cell carcinoma cells (RCCs). Infection of RCCs with a tropism-modified serotype 5/3 adenovirus expressing MDA-7/IL-24 (Ad.5/3-mda-7) caused plasma membrane clustering of CD95 and CD95 association with pro-caspase 8, effects that were enhanced by combined exposure to 17-N-allylamino-17-demethoxygeldanamycin (17AAG), As(2)O(3), or fenretinide and that correlated with enhanced cell killing. Knockdown of CD95 or expression of cellular FADD (Fas-associated protein with death domain)-like interleukin-1ß-converting enzyme inhibitory protein, short form (c-FLIP-s) blocked enhanced killing. Inhibition of ROS generation, elevated cytosolic Ca(2+), or de novo ceramide synthesis blocked Ad.5/3-mda-7 ± agent-induced CD95 activation and the enhancement of apoptosis. Ad.5/3-mda-7 increased ceramide levels in a PERK-dependent fashion that were responsible for elevated cytosolic Ca(2+) levels that promoted ROS generation; 17AAG did not further enhance cytokine-induced ceramide generation. In vivo, infection of RCC tumors with Ad.5/3-mda-7 suppressed the growth of infected tumors that was enhanced by exposure to 17AAG. Our data indicate that in RCCs, Ad.5/3-mda-7-induced ceramide generation plays a central role in tumor cell killing and inhibition of multiple signaling pathways may have utility in promoting MDA-7/IL-24 lethality in renal cancer.

Aggressive vertebral hemangioma masquerading as neurological disease in a pediatric patient.

Aggressive hemangioma is a rare vertebral lesion in pediatric patients which can present with deteriorating neurological function. It can mimic malignancy on imaging, particularly as it regularly has an extrasosseous soft tissue component. We present a case of a 13-year-old male who presented with a three month history of lower extremity weakness that was found to have an infiltrative mass at T10 with associated cord compression from epidural extension of the lesion. In this report we review the characteristic imaging findings associated with aggressive hemangioma, including its appearance on read-out segmented diffusion-weighted images. It is imperative that radiologists who interpret studies of children be aware that this lesion exists and what it looks like, as it can be associated with massive hemorrhage if encountered unexpectedly during surgery.

Sorafenib inhibits signal transducer and activator of transcription 3 signaling associated with growth arrest and apoptosis of medulloblastomas.

Medulloblastomas are the most frequent malignant brain tumors in children. Sorafenib (Nexavar, BAY43-9006), a multikinase inhibitor, blocks cell proliferation and induces apoptosis in a variety of tumor cells. Sorafenib inhibited proliferation and induced apoptosis in two established cell lines (Daoy and D283) and a primary culture (VC312) of human medulloblastomas. In addition, sorafenib inhibited phosphorylation of signal transducer and activator of transcription 3 (STAT3) in both cell lines and primary tumor cells. The inhibition of phosphorylated STAT3 (Tyr(705)) occurs in a dose- and time-dependent manner. In contrast, AKT (protein kinase B) was only decreased in D283 and VC312 medulloblastoma cells and mitogen-activated protein kinases (extracellular signal-regulated kinase 1/2) were not inhibited by sorafenib in these cells. Both D-type cyclins (D1, D2, and D3) and E-type cyclin were down-regulated by sorafenib. Also, expression of the antiapoptotic protein Mcl-1, a member of the Bcl-2 family, was decreased and correlated with apoptosis induced by sorafenib. Finally, sorafenib suppressed the growth of human medulloblastoma cells in a mouse xenograft model. Together, our data show that sorafenib blocks STAT3 signaling as well as expression of cell cycle and apoptosis regulatory proteins, associated with inhibition of cell proliferation and induction of apoptosis in medulloblastomas. These findings provide a rationale for treatment of pediatric medulloblastomas with sorafenib.

Spinal cord astrocytoma: a unique presentation of abdominal pain.

A previously healthy male presented at age 5 years with recurrent abdominal pain that occurred diffusely. The pain was severe enough to cause episodic screaming, especially at night with spontaneous resolution. The patient was initially treated for constipation but when motor symptoms began to develop, imaging revealed the cause of his pain to be a spinal cord mass. The tumor was treated with steroids, and biopsy confirmed a grade II spinal cord astrocytoma. We describe this unusual presentation of a pediatric spinal cord astrocytoma and review the literature.

Changes in Cerebral Oxygenation in Preterm Infants With Progressive Posthemorrhagic Ventricular Dilatation.

BACKGROUND: Optimal timing of intervention in neonatal progressive posthemorrhagic hydrocephalus is often a difficult decision. Unchecked hydrocephalus can lead to irreversible brain injury through impaired perfusion, while placement of a shunt is not without long-term morbidity. The purpose of this study was to assess the use of near-infrared spectroscopy to measure changes in regional cerebral oxygen saturation as an indicator of cerebral perfusion in infants with progressive posthemorrhagic ventricular dilatation. METHODS: Near-infrared spectroscopy was used to measure regional cerebral oxygen saturation for more than a one-hour period in infants within 24 hours of cranial ultrasound. Simultaneous pulse oximetry was recorded and oxygen extraction was calculated. Ventricular size was measured by ultrasound using the frontal-occipital horn ratio and compared with average oxygen saturation and oxygen extraction. Statistical analysis was done using the Spearman rank test and analysis of variance. RESULTS: Ventricular measurements were made in 20 very low birth weight premature infants with periventricular-intraventricular hemorrhage and 12 infants with normal ultrasound scans. Ventricular dilatation was associated with lower cerebral oxygen saturation and higher oxygen extraction (P < 0.001). Progressive ventricular dilatation was inversely related to changes in cerebral oxygen saturation (P < 0.001). CONCLUSIONS: Progressive posthemorrhagic ventricular dilatation is associated with a significant decrease in cerebral oxygenation and increase in oxygen extraction suggesting a decrease in cerebral perfusion. Near-infrared spectroscopy could potentially provide additional clinical information to assist in determining optimal timing of surgical intervention in preterm infants with progressive ventricular enlargement.

Graft subsidence after instrument-assisted anterior cervical fusion.

OBJECT: Bone grafts used in anterior cervical fusion (ACF) may subside postoperatively. The authors reviewed a recent series in which instrument-assisted ACF was performed to determine the degree of subsidence with respect to fusion length, use of segmental screws, and patient smoking status, age, and sex. METHODS: Charts and implant records were reviewed for all 70 patients who underwent instrument-assisted ACF during a 2-year period. The procedures, grafting materials, plate types/lengths, and patient smoking status were recorded. The immediate postoperative and follow-up lateral radiographs were analyzed. The plate lengths and lengths of the fused segments were measured in a standardized fashion. The mean intraoperative and follow-up fusion segment lengths were 54.3 and 51.9 mm, respectively. Greater subsidence occurred in multilevel fusions than in single-level fusions. There were noticeable changes in the position of plates or screws on 14 of 70 follow-up x-ray films. No new neurological deficits related to graft subsidence occurred, and the reoperation rate was 3%. There was no statistical relation between subsidence and the following variables: segmental fixation, smoking status, sex, age, or dowel size when corrected for length of the plate. Hardware migration correlated significantly with plate length in cases of two- and three-level fusions. CONCLUSIONS: The length of a fusion segment decreases in the immediate weeks following instrument-assisted ACF. Construct length is the most important determinant of subsidence. When designing multilevel cervical constructs, consideration of the effects of graft subsidence may help to avoid hardware-related complications.

Diagnosis of Erdheim-Chester disease by using computerized tomography-guided stereotactic biopsy of a caudate lesion. Case report.

The authors present the case of a 27-year-old woman with Erdheim-Chester disease (ECD) and extensive intracranial involvement, in whom the initial diagnosis of ECD was established based on computerized tomography (CT)-guided stereotactic biopsy of a caudate lesion. Erdheim-Chester disease is a rare non-Langerhans cell histiocytosis of unknown origin that is clinically characterized by bone pain, diabetes insipidus, and exophthalmos. The radiological hallmarks of the disease include symmetrical sclerosis of the long bones with epiphysial sparing and increased tracer uptake in lesions seen on scintigraphic imaging. Erdheim-Chester disease is characterized histologically by the presence of infiltrating lipid-laden histiocytes that commonly involve the retroperitoneum, orbits, skin, pericardium, lungs, and long bones. Although the occurrence of diabetes insipidus often precedes the diagnosis of ECD by more than a decade in most patients, magnetic resonance imaging- and CT-documented central nervous system involvement is exceedingly rare. In the setting of neurological involvement, neurosurgical biopsy has been reported seven times in the literature, with only one of these biopsies being the basis for the initial diagnosis of the disease. The authors' case represents only the second time the disease has been diagnosed by means of neurosurgical biopsy, highlighting the diagnostic difficulties that patients with EDC present. Skeletal radiographs were confirmatory in this case and this modality should be emphasized as the simplest and most direct route to the diagnosis. The degree of neurological involvement further distinguishes the case presented from prior reports in the literature. The multiple bilateral intraaxial lesions were intensely enhancing on contrast CT scans, distributed infra- and supratentorially, involving both white and gray matter, and associated with diffuse cerebral edema. The case presented is also remarkable by virtue of the symmetrical involvement of the caudate nuclei, representing the first such example documented in the literature. The diagnosis, treatment, and outcome in this patient are discussed, and a review of the literature is presented.

Delayed repair of myelomeningoceles.

OBJECTIVE: Myelomeningocele is a defect that typically is repaired surgically within the first few days of life in developed countries to minimize the risk of meningitis. If left unrepaired, these children may survive to have their meningocele sac epithelialize. The surgical reduction and closure of an epithelialized myelomeningocele represents a unique challenge for the neurosurgeon because it requires a modification of the typical closure technique. METHODS: Our 10 years' experience in 97 patients with the delayed (>6 months) repair of myelomeningoceles formed the basis of this report. RESULTS: We present repair techniques in a child with a myelomeningocele that was not repaired at birth and presented a surgical challenge. CONCLUSION: Delayed closure of myelomeningoceles is facilitated by lessons learned from our surgical experience during a medical missions to Guatemala.

Management of patients with cochlear implants and ventriculoperitoneal shunts.

OBJECTIVES: The aim of this study is to provide an overview of each device, discuss conditions that may predispose to the requirement of both devices, and consider pre- and post-operative issues arising from the co-existence of advanced technologies. In addition, relevant surgical anatomy and technique in the placement of both cochlear implant (CI) after ventriculoperitoneal shunt (VPS) and VPS after CI are reviewed. METHODS: Review of literature. RESULTS: Issues relevant to CI and VPS include predisposing conditions, magnetic resonance imaging compatibility, infectious risk, surgical technique, complication management, and a host of other issues. DISCUSSION: Patients with hydrocephalus and severe-to-profound hearing loss are a unique patient population with unique pre-, intra-, and post-operative issues. Thorough understanding of the indications, radiology, anatomy, technology, and potential complications can allow for these patients to achieve the full benefit of these lifechanging surgeries.

Craniosynostosis of the lambdoid suture.

Craniosynostosis affecting the lambdoid suture is uncommon. The definition of lambdoid craniosynostosis solely applies to those cases demonstrating true suture obliteration, similar to other forms of craniosynostosis. In patients presenting with posterior plagiocephaly, true lambdoid craniosynostosis must be differentiated from the much more common positional molding. It can occur in a unilateral form, a bilateral form, or as part of a complex craniosynostosis. In children with craniofacial syndromes, synostosis of the lambdoid suture most often is seen within the context of a pansynostotic picture. Chiari malformations are commonly seen in multisutural and syndromic types of craniosynostosis that affect the lambdoid sutures. Posterior cranial vault remodeling is recommended to provide adequate intracranial volume to allow for brain growth and to normalize the skull shape. Although many techniques have been described for the correction of lambdoid synostosis, optimal outcomes may result from those techniques based on the concept of occipital advancement.

Minimizing transfusion requirements for children undergoing craniosynostosis repair: the CHoR protocol.

OBJECT: Children with craniosynostosis may require cranial vault remodeling to prevent or relieve elevated intracranial pressure and to correct the underlying craniofacial abnormalities. The procedure is typically associated with significant blood loss and high transfusion rates. The risks associated with transfusions are well documented and include transmission of infectious agents, bacterial contamination, acute hemolytic reactions, transfusion-related lung injury, and transfusion-related immune modulation. This study presents the Children's Hospital of Richmond (CHoR) protocol, which was developed to reduce the rate of blood transfusion in infants undergoing primary craniosynostosis repair. METHODS: A retrospective chart review of pediatric patients treated between January 2003 and Febuary 2012 was performed. The CHoR protocol was instituted in November 2008, with the following 3 components; 1) the use of preoperative erythropoietin and iron therapy, 2) the use of an intraoperative blood recycling device, and 3) acceptance of a lower level of hemoglobin as a trigger for transfusion (< 7 g/dl). Patients who underwent surgery prior to the protocol implementation served as controls. RESULTS: A total of 60 children were included in the study, 32 of whom were treated with the CHoR protocol. The control (C) and protocol (P) groups were comparable with respect to patient age (7 vs 8.4 months, p = 0.145). Recombinant erythropoietin effectively raised the mean preoperative hemoglobin level in the P group (12 vs 9.7 g/dl, p < 0.001). Although adoption of more aggressive surgical vault remodeling in 2008 resulted in a higher estimated blood loss (212 vs 114.5 ml, p = 0.004) and length of surgery (4 vs 2.8 hours, p < 0.001), transfusion was performed in significantly fewer cases in the P group (56% vs 96%, p < 0.001). The mean length of stay in the hospital was shorter for the P group (2.6 vs 3.4 days, p < 0.001). CONCLUSIONS: A protocol that includes preoperative administration of recombinant erythropoietin, intraoperative autologous blood recycling, and accepting a lower transfusion trigger significantly decreased transfusion utilization (p < 0.001). A decreased length of stay (p < 0.001) was seen, although the authors did not investigate whether composite transfusion complication reductions led to better outcomes.

Sonographic localization of a nonpalpable shunt: Ultrasound-assisted ventricular shunt tap.

BACKGROUND: Patients frequently present to the emergency department (ED) for evaluation of cerebrospinal fluid (CSF) shunt malfunction, often requiring urgent management. A typical evaluation in the emergency room setting includes a thorough history and physical examination, noncontrasted head computed tomography (CT), shunt series, and occasionally a ventricular shunt tap. CASE DESCRIPTION: We present the case of a 53-year-old male who initially presented to the ED in acute status epilepticus. His history was notable for seizures and multiple craniectomies and cranioplasties with subsequent placement of a ventriculoperitoneal shunt secondary to traumatic brain injury. Imaging in the ED suggested possible shunt failure. No previous imaging was available for comparison, and therefore a ventricular shunt tap was attempted. Initially, the tap could not be performed, as the shunt was not palpable secondary to the thickness of his scalp and location of the reservoir near his complex cranial reconstruction site. We report, for the first time, the utility of emergency ultrasound (EUS) to aid in such an encounter. CONCLUSION: EUS revealed the exact location of his shunt reservoir, and therefore enabled the shunt tap, which ultimately led to the discovery of the patient's proximal shunt failure in a setting that may have otherwise been missed. The patient underwent urgent shunt revision with a good outcome.

Threatened ventriculostomy shunt exposure: augmenting native soft tissue coverage with acellular dermal matrix graft.

Avoiding threatened ventriculostomy shunt exposure in the pediatric population remains a difficult problem for the neurosurgeon and reconstructive surgeon. In this case series, the authors present a novel method of augmenting scalp soft tissue with acellular dermal matrix (ADM) in patients with a history of ventricular shunt revisions. Soft tissue augmentation with ADM successfully prevented shunt exposure in 3 patients with a history of shunt revision due to impending exposure following conventional techniques.

Dental surgery and anesthetic precautions of a patient with Down syndrome and juvenile rheumatoid arthritis: a case report.

Down syndrome and juvenile rheumatoid arthritis have been associated with ligament laxity, specifically the atlantoaxial ligament, which maintains the proper positioning of the cervical first and second vertebrae. The joint consists of different pathological processes, and it is paramount that individuals with either condition be screened appropriately before surgery is contemplated. The purpose of this paper was to present a case of an individual with both conditions and describe precautionary measures that were undertaken to safely complete dental treatment under general anesthesia and avoid morbidity.

Sorafenib and HDAC inhibitors synergize to kill CNS tumor cells.

The present studies were designed to determine whether the multi-kinase inhibitor sorafenib (Nexavar) interacted with histone deacetylase inhibitors to kill glioblastoma and medulloblastoma cells. In a dose-dependent fashion sorafenib lethality was enhanced in multiple genetically disparate primary human glioblastoma isolates by the HDAC inhibitor sodium valproate (Depakote). Drug exposure reduced phosphorylation of p70 S6K and of mTOR. Similar data to that with valproate were also obtained using the HDAC inhibitor vorinostat (Zolinza). Sorafenib and valproate also interacted to kill medulloblastoma and PNET cell lines. Treatment with sorafenib and HDAC inhibitors radio-sensitized both GBM and medulloblastoma cell lines. Knock down of death receptor (CD95) expression protected GBM cells from the drug combination, as did overexpression of c-FLIP-s, BCL-XL and dominant negative caspase 9. Knock down of PDGFRα recapitulated the effect of sorafenib in combination with HDAC inhibitors. Collectively, our data demonstrate that the combination of sorafenib and HDAC inhibitors kills through activation of the extrinsic pathway, and could represent a useful approach to treat CNS-derived tumors.