Cerebellar pleomorphic xanthoastrocytoma in the setting of neurofibromatosis type-I: Does it portend a different prognosis? A case report and systematic review.

BACKGROUND: Pleomorphic xanthoastrocytoma (PXA) is a rare brain tumor occurring supra- and infra-tentorially in both young adults and children. PXA is a benign tumor with a favorable prognosis. It is not traditionally considered as a neurofibromatosis type 1 (NF-1)-associated lesion, and its prognosis remains largely unknown, on the contrary to non-NF-1 PXA tumors. OBJECTIVE: Herein, we present a rare case of cerebellar PXA in a patient with NF-1 and performed systematic review of NF-1-associated PXA. METHOD: We present a case of NF-1-associated PXA arising in the cerebellar region. We also reviewed the literature in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines to identify published cases of cerebellar vs. non-cerebellar NF-1-associated PXA and NF1 vs. non-NF1 PXAs, highlighting their management paradigm, prognosis, and outcomes. RESULT: Our systematic review yielded only four previously reported cases of NF-1-associated PXAs in the cerebellar region. Our review suggests that infratentorial PXAs have a higher recurrence and lower survival rates than non-cerebellar NF-1-associated PXAs and non-NF1 PXAs in general. CONCLUSION: Early and precise diagnosis is important for these lesions with the aid of imaging features, histology, immunohistochemistry, and genetic markers. Surgical resection with goal of GTR remains the mainstay management strategy for PXA, with adjuvant therapy usually reserved for anaplastic or malignant lesions. The identification of BRAF-V600E mutation and role of BRAF inhibitors hold promise as a diagnostic tool and treatment modality, respectively, for PXAs, and their relationship to NF-1 is worth further exploration.

Symptomatic xanthogranuloma of the lateral ventricle in a pregnant patient treated with delayed resection: A case report and systematic review.

Intracranial xanthogranulomas (XG) are a rare benign histiocytic neoplasm and most often within the choroid. The majority are asymptomatic and are found incidentally on imaging or post-mortem examination or autopsy. We present a case of symptomatic XG in a pregnant patient who underwent a delayed transcortical, transventricular approach for lateral ventricle XG resection following the completion of her pregnancy. Four years post-operatively, the patient is neurologically intact and without recurrence. Our review of the literature showed differences among XG depending on location. The clinical and radiological features of XG are often indistinguishable from tumors arising from the choroid plexus and should be considered as a rare etiology in the differential of newly diagnosed intraventricular lesions.

Biomarkers of Pineal Region Tumors: A Review.

Background: The pineal gland, a small, pinecone-shaped organ deep within the brain, is responsible for producing melatonin. The gland consists of pineal parenchymal cells and glial cells that can form neoplasms. Pineal region neoplasms can also arise from germ cells and adjacent structures. This review focuses on detection of serum and cerebrospinal fluid (CSF) biomarkers of germ cell tumors and pineal parenchymal cell tumors, as these types comprise most neoplasms specific to the pineal region. Methods: For this review, we searched PubMed using the following keywords: biomarkers, germ cell tumor, germinoma, melatonin, pineal, pineal gland, pineal neoplasm, pinealoma, pineal parenchymal cell tumor, pineal region, and pineal tumor. We limited our search to full-text English articles and identified other relevant sources from the reference lists of identified articles. Results: Serum and CSF biomarker assays have a role in cases of suspected pineal germ cell or parenchymal neoplasms. Biomarkers including alpha-fetoprotein, beta-human chorionic gonadotropin, and placental alkaline phosphatase inform diagnosis and treatment and are important for monitoring germ cell tumor response to treatment. No biomarkers are currently available that inform diagnosis or treatment of pineal parenchymal tumors, although melatonin assays may have a role in monitoring response to treatment. Conclusion: Serum and CSF biomarkers in conjunction with clinical and radiographic evidence of a pineal region mass can inform the decision whether to undertake stereotactic biopsy or surgical excision or whether to proceed straight to medical treatment.

Advances in Neuro-Oncology Imaging Techniques.

BACKGROUND: Central nervous system (CNS) tumors are a rare but devastating malignancy, often robbing patients of the basic quality of life. Despite advances in our understanding of the CNS tumor disease processes, the prognosis for patients with CNS tumors remains poor. Better characterization and diagnostic and monitoring approaches are necessary to assist in diagnosis and treatment of CNS tumors. One important tool in the neuro-oncology armamentarium is the use of advanced imaging techniques. METHODS: We searched PubMed using the keywords neuro-oncology imaging, pseudoprogression, molecular imaging, and biomarkers. We limited our search to full-text English articles and identified other relevant articles from the reference lists of previously identified articles. RESULTS: Advances in imaging techniques have allowed investigators to explore various imaging modalities, from tumor characterization to differentiating pseudoprogression from tumor progression. Better imaging can result in better diagnostic approaches, greater and safer resection techniques, and improved monitoring of tumor progression. CONCLUSION: This review highlights advances in neuro-oncology imaging techniques and their clinical utility in the treatment and management of primary brain tumors.

A comprehensive next generation sequencing-based virome assessment in brain tissue suggests no major virus - tumor association.

Next generation sequencing (NGS) can globally interrogate the genetic composition of biological samples in an unbiased yet sensitive manner. The objective of this study was to utilize the capabilities of NGS to investigate the reported association between glioblastoma multiforme (GBM) and human cytomegalovirus (HCMV). A large-scale comprehensive virome assessment was performed on publicly available sequencing datasets from the Cancer Genome Atlas (TCGA), including RNA-seq datasets from primary GBM (n = 157), recurrent GBM (n = 13), low-grade gliomas (n = 514), recurrent low-grade gliomas (n = 17), and normal brain (n = 5), and whole genome sequencing (WGS) datasets from primary GBM (n = 51), recurrent GBM (n = 10), and normal matched blood samples (n = 20). In addition, RNA-seq datasets from MRI-guided biopsies (n = 92) and glioma stem-like cell cultures (n = 9) were analyzed. Sixty-four DNA-seq datasets from 11 meningiomas and their corresponding blood control samples were also analyzed. Finally, three primary GBM tissue samples were obtained, sequenced using RNA-seq, and analyzed. After in-depth analysis, the most robust virus findings were the detection of papillomavirus (HPV) and hepatitis B reads in the occasional LGG sample (4 samples and 1 sample, respectively). In addition, low numbers of virus reads were detected in several datasets but detailed investigation of these reads suggest that these findings likely represent artifacts or non-pathological infections. For example, all of the sporadic low level HCMV reads were found to map to the immediate early promoter intimating that they likely originated from laboratory expression vector contamination. Despite the detection of low numbers of Epstein-Barr virus reads in some samples, these likely originated from infiltrating B-cells. Finally, human herpesvirus 6 and 7 aligned viral reads were identified in all DNA-seq and a few RNA-seq datasets but detailed analysis demonstrated that these were likely derived from the homologous human telomeric-like repeats. Other low abundance viral reads were detected in some samples but for most viruses, the reads likely represent artifacts or incidental infections. This analysis argues against associations between most known viruses and GBM or mengiomas. Nevertheless, there may be a low percentage association between HPV and/or hepatitis B and LGGs.

Insular and Sylvian Fissure Dermoid Cyst with Giant Cell Reactivity: Case Report and Review of Literature.

BACKGROUND: Dermoid cysts are rare intracranial tumors that are most commonly found infratentorially and along the midline. Characterized by slow growth and often found incidentally, these lesions can nonetheless have severe complications, notably rupture leading to chemical meningitis. They infrequently present as a supratentorial and lateralized mass. As such, sylvian fissure dermoid cysts are exquisitely rare. We present a rare case of a dermoid cyst with giant cell reactivity suggestive of focal rupture and chronic inflammation. CASE DESCRIPTION: A 61-year-old female presented with new-onset seizures. Magnetic resonance imaging revealed a right insular mass measuring 4.3 × 4.5 cm with compression of the ipsilateral frontal and temporal lobes. The mass was nonenhancing; however, it was bright on diffusion-weighted imaging, suggesting a dermoid cyst. She underwent craniotomy for tumor resection. Histologic analysis revealed keratinizing squamous epithelium, sebaceous glands, and hair follicles associated with giant cell reaction involving the capsule of the cyst consisted with dermoid cyst. At 2.5 years post operation, she is seizure free and without evidence of recurrence. CONCLUSION: The dermoid cyst in our patient was not grossly ruptured, but histopathologic analysis revealed giant cell reactivity, which may indicate focal rupture or chronic inflammation. The relationship between rupture of dermoid cysts and inflammation is not well elucidated. It is not known whether symptoms occur immediately after rupture or as an acute manifestation of a chronic process following rupture. As these lesions are quite rare and rupture is even rarer, more diligence on our part regarding details of histopathology for dermoid cysts is necessary.

Primary High-Grade Osteosarcoma of the Clivus: A Case Report and Literature Review.

BACKGROUND: Osteosarcoma is the second most common primary tumor of the skeletal system and the most common primary bone tumor. Usually occurring at the metaphysis of long bones, osteosarcomas are highly aggressive lesions that comprise osteoid-producing spindle cells. Craniofacial osteosarcomas comprise <8% and are believed to be less aggressive and lower grade. Primary osteosarcomas of the skull and skull base comprise <2% of all skull tumors. Osteosarcomas originating from the clivus are rare. We present a case of a primar, high-grade clival osteosarcoma. CASE DESCRIPTION: A 29-year-old man presented to our institution with a progressively worsening right frontal headache for 3 weeks. There were no sensory or cranial nerve deficits. Computed tomography revealed a destructive mass involving the clivus with extension into the left sphenoid sinus. Magnetic resonance imaging revealed a homogenously enhancing lesion measuring 2.7 × 2.5 × 3.2 cm. The patient underwent endonasal transphenoidal surgery for gross total resection. The histopathologic analysis revealed proliferation of malignant-appearing spindled and epithelioid cells with associated osteoclast-like giant cells and a small area of osteoid production. The analysis was consistent with high-grade osteosarcoma. The patient did well and was discharged on postoperative day 2. He was referred for adjuvant radiation therapy and chemotherapy. Two-year follow-up showed postoperative changes and clival expansion caused by packing material. CONCLUSIONS: Osteosarcoma is a highly malignant neoplasm. These lesions are usually found in the extremities; however, they may rarely present in the craniofacial region. Clival osteosarcomas are relatively infrequent. We present a case of a primary clival osteosarcoma with high-grade pathology.

Benign Sacral Metastatic Meningioma: A Rare Entity.

BACKGROUND: Meningiomas are common intracranial tumors with a low metastatic rate. Those that do metastasize often show histopathologic signs of malignancy. In rare cases, the primary and secondary tumors are histologically benign. CASE REPORT: We report the case of a 57-year-old female with a histologically benign intracranial meningioma that metastasized to the sacrum. The patient had a long history of intracranial meningioma with multiple recurrences. At each recurrence, histopathologic examination of the resected tumor showed no signs of malignancy. The sacral meningioma was biopsied and found to be histologically benign. The patient was treated with radiotherapy (54 Gy in 30 fractions), and her symptoms resolved. Six months later, the patient developed left leg weakness. Magnetic resonance imaging showed growth of her intracranial mass for which she underwent a craniotomy for tumor resection. Pathologic evaluation showed evidence of benign meningioma without atypical features. She recovered well from this procedure and returned to her baseline in several weeks. CONCLUSION: After treatment, the patient had no signs of radiographic progression in either location.

Adjuvant enoxaparin therapy may decrease the incidence of postoperative thrombotic events though does not increase the incidence of postoperative intracranial hemorrhage in patients with meningiomas.

Patients with brain tumors including intracranial meningiomas are at increased risk for developing deep vein thrombosis (DVTs) and suffering thromboembolic events (VTEs). Many surgeons are concerned that early use of low dose enoxaparin may increase the risk of intracranial hemorrhage which outweighs the benefit of DVT/VTE reduction. We aimed to address concerns around the use of enoxaparin after meningioma resection in the development of postoperative intracranial hemorrhages and DVT/VTEs. This is a retrospective review of 86 patients with intracranial meningiomas who underwent craniectomy and surgical resection of the mass, treated by one attending surgeon at UCSF Medical Center between 2000 and 2005. Within 48 h after surgery patients treated 2003-2005 routinely received enoxaparin therapy unless there was documented intracranial hemorrhage, lumbar subarachnoid drain, enoxaparin hypersensitivity, or thrombocytopenia (n = 24). These were compared to a cohort treated 2000-2002 who did not receive the drug (n = 62). Exclusion criteria were prior VTEs or coagulopathies. The groups were similar in tumor and surgical characteristics. Enoxaparin therapy did not increase the incidence of intracranial hemorrhage following surgical meningioma resection and the incidence of DVTs/VTEs was 0% (n = 0) versus 4.8% (n = 3) in the non-enoxaparin group. Results did not reach statistical significance. In this retrospective study, postoperative administration of enoxaparin following meningioma resection does not increase the risk of intracranial hematoma though enoxaparin administration may slightly decrease the incidence of post-surgical thromboembolic events. Due to study design and power, we were not able to demonstrate DVT/VTE reduction with statistical significance.

Amplifying small amounts of tumor DNA allows detection of DNA copy number abberations with array-CGH.

Array comparative genomic hybridization (aCGH) is a powerful tool to detect relative DNA copy number at a resolution limited only by the coverage of bacterial artificial chromosomes (BACs) used to print the genomic array. The amount of DNA needed to perform a reliable aCGH analysis has been a limiting factor, especially on minute tissue samples where limited DNA is available. Here we report a simple, highly sensitive and reliable aCGH method to analyze samples of no more than 1 ng genomic DNA. The speed and simplicity of the technique are ideal for studies on small clinical samples such as needle biopsies.

Cervical spine trauma in the pediatric patient.

Injuries to the pediatric cervical spine occur infrequently. Numerous unique anatomic and biomechanical features of the pediatric spine render it much more flexible than the adult spine. These features give rise to significant differences in the presentation, diagnosis, treatment, and prognosis of pediatric cervical trauma compared with adults. Younger children more often suffer injury to the upper cervical spine with greater neurologic injury and fewer fractures. Once the child reaches the age of 10 years, he or she develops a more adult-type spine, and injuries are thus more similar to those seen in the adult population. The unique anatomic and biomechanical differences in the pediatric spine are discussed, along with the various common and unique injuries.

Genetic aberrations in gliomatosis cerebri.

OBJECTIVE: Identifying the genetic alterations in gliomatosis cerebri (GC) may yield clinically useful prognostic markers and provide clues as to whether GC represents a distinct pathological entity or is an extreme form of diffusely infiltrative glioma. METHODS: Clinical histories, treatment histories, magnetic resonance imaging, and pathological analysis of patients with GC treated at either the University of California San Francisco or the Mayo Clinic were reviewed. Degenerate oligonucleotide-primed polymerase chain reaction was performed on biopsy samples of GC. Comparative genomic hybridization was used to determine relative deoxyribonucleic acid copy number. We evaluated relationships of clinical and radiological treatment and comparative genomic hybridization data to survival after diagnosis with Cox regression analysis. RESULTS: Radiographic analysis and biopsy specimens were available for study in 29 patients (17 men, 12 women). Comparative genomic hybridization was successfully performed in 22 patients. Contrast enhancement was the most significant predictor of poor survival (P = 0.0026). Loss of chromosomes 13q and 10q and gains of 7q were also independent significant predictors of poor survival (P = 0.0032, 0.0335, and 0.0487, respectively). Patients treated with temozolomide or with radiation therapy had improved survival, but this effect did not reach statistical significance (P = 0.180 and 0.124, respectively). CONCLUSION: Chromosomal aberrations associated with aggressive astrocytomas are predictors of poor outcome in patients with GC. This suggests that GC may be an architectural variant of diffuse astrocytomas. The presence of these aberrations and the presence of any contrast enhancement on magnetic resonance imaging scans are possible stratifiers for patients with GC. Stratification of GC into higher- and lower-grade forms may be useful in tailoring treatments to patients with this disease.

Assessment of image guided accuracy in a skull model: comparison of frameless stereotaxy techniques vs. frame-based localization.

INTRODUCTION: The use of image-guided systems (IGS) for brain biopsy has increased in neurosurgical practice. We sought to evaluate the accuracy of a plastic, disposable burr hole mounted guide for stereotactic biopsy using an IGS and compare the results of different targeting methods with those of frame based localization. METHODS: MRIs were performed on a skull model with mounted fiducials with a stereotactic frame in place and data was loaded onto the Stealth IGS. The model was placed in a Mayfield head holder and fixed to the OR table. Registration of imaging to physical space was carried out. Using three different targeting methods on the Stealth IGS, the distance between the target and the predicted position of the target, the offset error, was measured in three dimensions and confirmed by 2 observers. A sum of squares for the 3 offset errors in all planes was used to calculate the summed vector error. The same MRI dataset used with the Cosman-Roberts-Wells (CRW) stereotactic frame for comparison. The summed vector error was calculated in the same manner to compare the accuracy of targeting with these guides to the frame-based CRW system. RESULTS: For frameless stereotaxy using the "Straight- guide 4 2D" targeting method the mean error was 2.58 +/- 0.51 mm (n=12). The vector error was 5.23 +/- 0.54 (n=4). For the registration set and target using the "Offset- guide 4 2D" targeting method the mean error was 1.66 +/- 0.36 mm (n=12). The vector error was 3.32 +/- 0.72 (n=4). The best localization was obtained with the "probe's eye" planning and targeting. The mean error was 0.33 +/- 0.16 mm (n=12). The vector error was 1.0 +/- 0.28 (n=4). We found a statistical difference between the different techniques (P<0.001) (Kruskal-Wallis One Way Analysis of Variance on Ranks). An all pairwise multiple comparison procedure (Holm-Sidak method) found an overall significance level = 0.05. For the frame-based CRW the mean error from the target was 1.03 +/- 0.19 mm (n=18) and the mean target localization error vector was 2.23 +/- 0.14 (n=6). We found a statistically significant difference between NDT guide "Probes Eye" vs. the MR-CRW (P=0.003, Mann-Whitney Rank Sum Test). CONCLUSIONS: These results indicate that using MR imaging, surgical planning software and the skull mounted Navigus-DT with the probe's eye view option for targeting, localization accuracy appears to fall within acceptable ranges compared with frame-based methods which have been the standards for stereotactic brain biopsy and functional neurosurgery. Furthermore, there may be considerable differences in accuracy between different targeting methods.

Effects of 23.4% sodium chloride solution in reducing intracranial pressure in patients with traumatic brain injury: a preliminary study.

OBJECTIVE: Mannitol is the standard of care for patients with increased intracranial pressure (ICP), but multiple administrations of mannitol risk renal toxicity and fluid accumulation in the brain parenchyma with consequent worsening of cerebral edema. This preliminary study assessed the safety and efficacy of small-volume injections of 23.4% sodium chloride solution for the treatment of intracranial hypertension in patients with traumatic brain injury who became tolerant to mannitol. METHODS: We retrospectively reviewed the charts of 13 adult patients with traumatic brain injury who received mannitol and 23.4% sodium chloride independently for the treatment of intracranial hypertension at San Francisco General Hospital between January and October 2003. Charts were reviewed to determine ICP, cerebral perfusion pressure, mean arterial pressure, serum sodium values, and serum osmolarity before and after treatment with 23.4% sodium chloride and mannitol. Complications were noted. RESULTS: The mean reductions in ICP after treatment were significant for both mannitol (P < 0.001) and hypertonic saline (P < 0.001); there were no significant differences between reductions in ICP when comparing the two agents (P = 0.174). The ICP reduction observed for hypertonic saline was durable, and its mean duration of effect (96 min) was significantly longer than that of mannitol treatment (59 min) (P = 0.016). No complications were associated with treatment with hypertonic saline. CONCLUSION: This study suggests that 23.4% hypertonic saline is a safe and effective treatment for elevated ICP in patients after traumatic brain injury. These results warrant a rigorous evaluation of its efficacy as compared to mannitol in a prospective randomized controlled trial.

Radiation-induced atypical meningioma with rapid growth in a 13-year-old girl. Case report.

This case illustrates the potential growth rate of an atypical meningioma in a pediatric patient, emphasizes one of the potential risks after therapeutic radiation, and underscores the importance of clinical evaluation and follow up of the symptomatic patient after tumor resection and radiation therapy. The authors report a case of a radiation-induced atypical meningioma of the olfactory groove in a 13-year-old girl who received 36 Gy of radiation to the craniospinal axis and 72 Gy to the primary site of a primitive neuroectodermal epithelial tumor of the left parietooccipital lobe when she was 4 years of age. This tumor was not present on routine magnetic resonance imaging performed 13 months prior to the discovery of this lesion or on computerized tomography scanning obtained 6 months prior to the discovery of this tumor. At the time of its discovery, the tumor was 5 x 5 x 4 cm. This tumor was resected and the patient's symptoms improved. This case illustrates the importance of continued close follow up after cranial irradiation in the pediatric population.

Surgical resection and permanent brachytherapy for recurrent atypical and malignant meningioma.

OBJECTIVE: Recurrent atypical and malignant meningiomas are difficult to treat successfully. Chemotherapy to date has been unsuccessful, and radiosurgery is limited to smaller tumors. Reoperation alone provides limited tumor control and limited prolonged survival. The addition of brachytherapy at the time of operation is an option. Here, we report the results of our series of patients with recurrent malignant meningioma treated with resection and brachytherapy with permanent low-dose (125)I. METHODS: The charts of patients in our database with recurrent atypical and malignant meningiomas treated by surgical resection and permanent (125)I brachytherapy at the University of California, San Francisco, between 1988 and 2002 were selected for this study. Calculations of disease-free survival and overall survival curves were made by the Kaplan-Meier actuarial method. Univariate analysis between Kaplan-Meier curves was based on the log-rank statistic, with a significance level set at a value of P

Nonsaccular aneurysms of the azygos anterior cerebral artery.

OBJECT: The azygos or undivided anterior cerebral artery (ACA) is a rare variant, and aneurysms associated with this variant are particularly rare. Most reported azygos ACA aneurysms are saccular, but the authors encountered four patients with this variant who had nonsaccular aneurysms. A review of the management of these lesions and this morphological distinction is presented. METHODS: A retrospective review of patients with aneurysms treated over a 6-year period identified five Type I (according to the Baptista classification) azygos ACA lesions, of which four were nonsaccular. Aneurysms associated with other ACA variants (Baptista Types II and III) were excluded. Azygos ACA aneurysms accounted for 0.5% of all treated lesions and 1.7% of all ACA and anterior communicating artery aneurysms. One lesion in this series was located proximally at the azygos ACA origin, and three were located distally. All four aneurysms were large (>10 mm in diameter), and two were thrombotic. All aneurysms were treated with microsurgical clip occlusion. CONCLUSIONS: Azygos ACA aneurysms are rare, and may have unusual nonsaccular anatomy (for example, fusiform shape, broad base, complex branching, and/or thrombus in the lumen). The nonsaccular morphology of these aneurysms may render them unsuitable for endovascular coil placement, and may complicate their microsurgical management.