Cavernous angioma after chemotherapy for desmoplastic/nodular medulloblastoma associated with anhidrotic ectodermal dysplasia.

PURPOSE: While cavernous angioma (CVA) after cranial irradiation has been documented, its development after high-dose chemotherapy with autologous peripheral blood stem cell transplantation (PBSCT) has not. We present a patient with desmoplastic/nodular medulloblastoma (DNMB) associated with anhidrotic ectodermal dysplasia (AED) who developed CVA 2 years after high-dose chemotherapy and PBSCT. METHODS: A 1-year-old boy with ingravescent vomiting was admitted to our institute. He presented with a large head, a depressed nasal bridge, low-set ears, thick lips with peg-shaped teeth, hypohidrosis, sparse hair, thin atrophic skin, scaly dermatitis with frontal bossing, and a bulging anterior fontanel. Neuroradiological examination revealed multiple cerebellar masses with heterogeneous enhancement and speckled calcifications and severe obstructive hydrocephalus. The histological diagnosis of surgical specimens was DNMB, and he underwent postoperative multiple-drug chemotherapy with autologous PBSCT. The outcome was favorable and he did not undergo radiotherapy. RESULTS: After 2 years, intracranial hemorrhage was detected at his regular radiological check-up and he again underwent surgery. The histological diagnosis was CVA. CONCLUSIONS: To our knowledge, this is the first report of AED-associated DNMB and CVA.

Multifunctional Fluoropolymer-Engineered Magnetic Nanoparticles to Facilitate Blood-Brain Barrier Penetration and Effective Gene Silencing in Medulloblastoma.

Patients with brain cancers including medulloblastoma lack treatments that are effective long-term and without side effects. In this study, a multifunctional fluoropolymer-engineered iron oxide nanoparticle gene-therapeutic platform is presented to overcome these challenges. The fluoropolymers are designed and synthesized to incorporate various properties including robust anchoring moieties for efficient surface coating, cationic components to facilitate short interference RNA (siRNA) binding, and a fluorinated tail to ensure stability in serum. The blood-brain barrier (BBB) tailored system demonstrates enhanced BBB penetration, facilitates delivery of functionally active siRNA to medulloblastoma cells, and delivers a significant, almost complete block in protein expression within an in vitro extracellular acidic environment (pH 6.7) - as favored by most cancer cells. In vivo, it effectively crosses an intact BBB, provides contrast for magnetic resonance imaging (MRI), and delivers siRNA capable of slowing tumor growth without causing signs of toxicity - meaning it possesses a safe theranostic function. The pioneering methodology applied shows significant promise in the advancement of brain and tumor microenvironment-focused MRI-siRNA theranostics for the better treatment and diagnosis of medulloblastoma.

Preoperative liquid embolization of cerebeller hemangioblastomas using N-butyl cyanoacrylate.

INTRODUCTION: We aim to present and discuss clinical outcomes of preoperative liquid embolization of hemangioblastomas (HB) using N-butyl cyanoacrylate (NBCA). METHODS: From 1999 through 2010, 19 patients presenting with symptoms of vertigo and/or headaches were diagnosed with HB based on preoperative magnetic resonance imaging and cerebral angiographic findings at our institution. Preoperative embolization with NBCA was performed on tumors in 10 of 21 operations for 19 patients. For each of these patients, the lesion was pathologically confirmed as HB. RESULTS: Embolization had a favorable outcome in all patients. No permanent neurological complications were observed after preoperative embolization using NBCA. However, thalamic infarction and minor hemorrhage were observed in two patients with cerebellar HB. CONCLUSION: The authors recommend NBCA as an embolization material for large cerebellar HB.

Treatment-induced remission of medulloblastoma using a chemotherapeutic regimen devoid of vincristine in a child with Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth (cmt) disease is the most common form of inherited neuropathy. Core features include peripheral neuropathy and secondary axonal degeneration, with a noted distal predominance of limb-muscle wasting, weakness, and sensory loss. Given the significant prevalence of cmt, superimposed neoplastic disease can be encountered within this patient population. Malignancies that are treated with vincristine (a microtubule-targeting agent), even at low doses as part of standard treatment, pose a significant challenge for patients with cmt. Here, we present the case of a child with cmt who was successfully treated for medulloblastoma without vincristine, a standard drug used for treatment of that disease, to avoid the risk of severe debilitating neuropathy. This report is the first of a patient successfully treated for medulloblastoma without vincristine.

[Medulloblastoma with mandibular metastasis after complete remission of the central nervous system lesions].

A 6-year-old boy presented with headache and vomiting. Brain and spinal MRI demonstrated a large mass in the cerebellar vermis and 4th ventricle and showed thick spinal subarachnoid dissemination. Suboccipital craniotomy was performed and the tumor was totally removed. The histological diagnosis was medulloblastoma. The patient subsequently received craniospinal irradiation, and also received systemic and intrathecal perfusion chemotherapy. Then complete remission was achieved 10 months after operation. Three years later, however, a swelling at the left mandibular angle appeared. A CT scan revealed osteosclerotic lesion. After biopsy was performed, the specimen was detected infiltration of medulloblastoma cells. Bone scintigram showed a single lesion and MRI of brain and spinal cord revealed no recurrence of the central nervous system lesions. He underwent local irradiation and systemic chemotherapy with ICE regimen. This is the rare case of extracranial metastasis following remission of medulloblastoma in childhood.

Direct transcranial puncture for Onyx embolization of a cerebellar hemangioblastoma.

Intracranial hemangioblastomas are benign but hypervascular tumors, most commonly located in the cerebellum, which are difficult to resect without significant operative blood loss. While preoperative embolization may decrease the amount of operative bleeding, the vascular supply of cerebellar hemangioblastomas frequently precludes safe embolization by an endovascular route due to the risk of thromboembolic vertebrobasilar infarction. Direct puncture embolization overcomes many of the limitations of endovascular embolization but its safety and feasibility for intracranial tumors is unknown. We report a 48-year-old man who was diagnosed with a large cerebellar mass after presenting with headaches and gait ataxia. Based on diagnostic angiography, which demonstrated a highly vascular tumor supplied by the posterior inferior cerebellar and posterior meningeal arteries, we decided to embolize the tumor by a direct transcranial puncture approach. After trephinating the skull in a standard fashion, a catheter-needle construct, composed of an Echelon 10 microcatheter (ev3 Endovascular, Plymouth, MN, USA) placed into a 21-gauge spinal needle, was inserted into the tumor under biplanar angiographic guidance. Using continuous angiographic monitoring, 9cc of Onyx 34 (ev3 Endovascular) was injected through the catheter, resulting in 75% tumor devascularization without evidence of complications. The patient was taken directly to surgery where a gross total resection of the hemangioblastoma was achieved with an acceptable operative blood loss. At his 2 year follow-up, the patient was neurologically intact without neuroimaging evidence of residual tumor. We describe, to our knowledge, the first case of direct transcranial puncture for preoperative embolization of a cerebellar hemangioblastoma.

Embolization of intra-axial hypervascular tumors with Onyx: report of three cases.

Complete surgical resection of intra-axial hypervascular tumors located in the posterior fossa, in particular hemangioblastomas, may be challenging due to tumor location, mass effect and excessive bleeding. Embolization of these lesions can be done preoperatively or as a palliative measure in patients who are not surgical candidates. Preoperative embolization may reduce intraoperative blood loss, shorten surgical time and increase the chance of a complete resection. However, the safety and effectiveness of this procedure is still a matter of debate. Three cases of intra-axial hypervascular tumors in the posterior fossa (two confirmed hemangioblastomas) that were embolized using a non-adhesive liquid embolic agent (Onyx) are reported.

N-butyl 2-cyanoacrylate (n-BCA) embolization of a cerebellar hemangioblastoma.

Hemangioblastomas (HBs) are highly vascular tumors whose resection can be associated with significant bleeding. Angioembolization has been used as an adjunct to surgical therapy, but particle embolization of cerebellar HBs has been associated with hemorrhage and resultant morbidity and mortality. We present a case of successful n-BCA embolization of an HB of the cerebellum.

Complete preoperative embolization of hemangioblastoma vessels with Onyx 18.

The authors present a preliminary experience with ethyl-enevinylalcohol copolymer (Onyx) for hemangioblastoma vessel embolization before surgical resection. The patient presented with neck pain, dizziness, blurred vision, vomiting, and loss of balance. Diagnostic imaging revealed a posterior fossa cystic mass with a nodular component. Angiography demonstrated a significant vascular blush with arteriovenous shunting that was characteristic of a hemangioblastoma. Tumor vessels originating off the left posterior inferior cerebellar artery were embolized before surgery using Onyx 18 (ev3, Covidien Vascular Therapies, Mansfield, MA, USA). This resulted in complete obliteration of all tumor vessels, transforming a highly vascular tumor into an avascular mass. A safe and uneventful surgical resection was performed the next day. Onyx is a valuable embolic agent for preoperative hemangioblastoma vessel embolization. Because of its low viscosity, Onyx penetrates deeply into the tumor vasculature and allows complete obliteration of tumor vessels. Risks of the intervention have to be carefully weighed against the benefits. If preoperative embolization is indicated, the use of Onyx should be strongly considered.

Hemangiopericytoma of the cerebellopontine angle: a case report and review of the literature.

BACKGROUND: Intracranial hemangiopericytoma represents a rare intracranial tumor that is typically difficult to distinguish from meningioma based on clinical presentation and radiographic findings. These inherently aggressive neoplasms have been observed to occur in numerous intracranial compartments; however, isolated involvement of the CPA is essentially unreported. The authors present a case of a young lady with presumed right acoustic schwannoma, which proved to be HPC on histopathology. The case is described; and a review of the literature pertaining to the diagnosis, optimal management, and follow-up for these lesions is provided. CASE DESCRIPTION: A 37-year-old Asian woman presented with a 7-month history of right ear and mandible numbness, as well as subjective hearing loss involving the right ear. Magnetic resonance imaging demonstrated the presence of a homogeneously enhancing extraaxial lesion in the right CPA, radiographically suggestive of an acoustic schwannoma. The lesion proved to be an intracranial HPC on histologic sections. Review of the neurosurgical literature yielded only one prior detailed account of HPC confined to the CPA. The patient underwent right retrosigmoid craniotomy for gross total resection of the mass, followed by stereotactic radiotherapy several weeks postoperatively. CONCLUSION: Given the fundamentally different treatment approach for HPCs over other more common CPA tumors, it is imperative that the treating surgeon consider this rare diagnosis when evaluating patients with lesions localized to this area. Specifically, gross total resection, followed by adjuvant SRT, provides patients with the highest probability for disease-free survival, based on current evidence in the neurosurgical literature.

Pre-operative endovascular embolization of a cerebellar haemangioblastoma. A case report.

OBJECTIVE: To present an interesting case of pre-operative embolization of a cerebellar haemangioblastoma. CLINICAL PRESENTATION AND INTERVENTION: A 36-year-old male presented with gradual, progressive headache and a positive family history of von Hippel-Lindau syndrome. MRI of the brain revealed a right cerebellar solid mass and cerebral angiography demonstrated its extensive hypervascular nature. The mass was embolized with polyvinyl alcohol prior to surgical resection, which resulted in improvement of the patient's symptoms. CONCLUSION: Pre-operative embolization of a haemangioblastoma is a useful procedure that can potentially decrease the morbidity and mortality of its surgical resection.

Immunogene therapy of recurrent glioblastoma multiforme with a liposomally encapsulated replication-incompetent Semliki forest virus vector carrying the human interleukin-12 gene--a phase I/II clinical protocol.

Glioblastoma multiforme (GBM) is an incurable brain tumor resistant to standard treatment modalities such as surgery, radiation, and chemotherapy. Since recurrent GBM tends to develop predominantly within the infiltrative rim surrounding the primary tumor focus, novel therapy strategies need in addition to focal tumor destruction to target this somewhat diffuse area. This is a phase I/II clinical study in adult patients with recurrent GBM which is aimed at evaluating biological safety, maximum tolerated dose, and antitumor efficacy of a genetically modified replication-disabled Semliki forest virus vector (SFV) carrying the human interleukin 12 (IL-12) gene and encapsulated in cationic liposomes (LSFV-IL12). The vector will be administered in doses of 1 x 10(7)-1 x 10(9) infectious particles by continuous intratumoral infusion, thus exploiting the advantages of convection-enhanced drug delivery in the brain. The present protocol is also designed to investigate systemic and local immune response and to identify factors predicting tumor response to LSFV-IL12 therapy, such as volume of extracellular space of the tumor, volume of contrast enhancing lesion, and immune status of the patients. SFV, an insect alphavirus, infects mitotic and non-mitotic cells and triggers apoptosis in tumor cells within 48-72 h. Preclinical work with the LSFV-IL12 vector in breast and prostate cancer animal models demonstrated its biosafety and some antitumor efficacy. An ongoing phase I clinical study in patients with melanoma and renal cell carcinoma seems also to confirm the biosafety of intravenously administered vectors. This protocol will be the first study of SFV-IL12 therapy of human recurrent GBM.