Primary intracranial dural-based synovial sarcoma with an unusual SYT fluorescence in situ hybridization pattern.

The authors present the case of an elderly man with a primary dural-based intracranial synovial sarcoma. Histological and immunohistochemical profiles of the lesion were diagnostic for a synovial sarcoma, and molecular studies using fluorescence in situ hybridization were compatible with a synovial sarcoma. A wide array of spindle cell neoplasms has been described as originating in the dura. To the authors' knowledge, however, this is only the second primary dura-based intracranial synovial sarcoma ever reported, emphasizing the importance of a broad differential diagnosis when encountering spindle cell lesions of the meninges.

Bevacizumab and irinotecan therapy in glioblastoma multiforme: a series of 13 cases.

OBJECT: Endothelial proliferation has been recognized as a marker of high-grade or aggressive glioma. Bevacizumab is a humanized immunoglobulin G1 monoclonal antibody to vascular endothelial growth factor that has been shown to have activity in malignant gliomas when combined with irinotecan. The authors report on a case series of 13 patients with recurrent heavily pretreated malignant glioma that was treated with the combination of bevacizumab and irinotecan. METHODS: Standard therapy with primary resection followed by adjuvant chemotherapy and radiation had failed in all patients. The median number of therapies applied, including initial surgery, was 5 (range 3-7 therapies). Nine patients were started on bevacizumab at a dose of 5 mg/m2 every 2 weeks. Four patients received bevacizumab at a dose of 10 mg/m2; irinotecan was given at a dose of 125 mg/m2 every week for 3 weeks. RESULTS: Of the 13 treated patients, 10 (77%) had a radiologically demonstrated partial response and 3 (23%) had stable disease. Six patients (46%) had a clinical response. The median time to disease progression while on treatment was 24 weeks. The median overall survival was 27 weeks. The disease progressed in 8 patients, despite an initial response. Five patients are still responding to therapy. Six of the 8 patients whose disease progressed have died. Bevacizumab was discontinued in 2 patients because of nonfatal intracranial bleeding. CONCLUSIONS: The combination of bevacizumab and irinotecan is safe and has excellent activity even in this relapsed, heavily pretreated population of patients with high-grade malignant glioma, most of whom would not be candidates for clinical trials.

Long-Term Outcomes After Stereotactic Radiosurgery for Spine Metastases: Radiation Dose-Response for Late Toxicity.

PURPOSE: To document the 5- and 10-year rates of late toxicity and vertebral compression fracture (VCF) in long-term survivors after stereotactic radiosurgery for spine metastases. METHODS AND MATERIALS: A retrospective review was performed on 562 patients treated with SRS for spine metastases between April 2001 and July 2011. Selecting those with at least 5-year survival after SRS, included were 43 patients who collectively underwent 84 treatments at 54 spine sites. Most were treated with single-fraction stereotactic radiosurgery to a median dose of 16 Gy (range, 12-24 Gy), and 56% of sites had received prior external beam radiation therapy. Late toxicities and VCFs occurring in the absence of tumor progression were recorded. Binary logistic regression was used to identify predictors of late complications. RESULTS: Nine patients (17% of treatment sites) developed grade ≥2 late toxicities at a median time of 12.8 months (range, 4.2-59.0 months). Actuarial 5- and 10-year rates of grade ≥2 late toxicity were 17% and 17%, respectively. On multivariate analysis, only cumulative biologically effective dose (BED3) > 200 Gy (or EQD22Gy [2-Gy equivalent dose calculated using an α/ß ratio of 2] > 130 Gy) was associated with grade ≥2 late toxicity (P = .036). Maximum point BED3 > 110 Gy (or EQD22Gy > 70 Gy) to spinal cord or cauda equina was associated with grade ≥2 late neuropathy (P = .017). Nine VCFs (18%) occurred at a median time of 10.2 months (range, 3.2-57.2 months), with 5- and 10-year VCF rates of 17% and 17%, respectively. CONCLUSION: Stereotactic radiosurgery for primary treatment and reirradiation of spinal metastases is associated with a moderate risk of late toxicity with 10-year follow-up. Risk of late toxicity significantly increases with cumulative BED3 > 200 Gy and spinal cord or cauda equina point BED3 > 110 Gy. Patients remain at moderate risk of VCF up to 5 years after treatment, with a plateau in incidence thereafter up to 10 years.

Autologous glioma cell vaccine admixed with interleukin-4 gene transfected fibroblasts in the treatment of patients with malignant gliomas.

BACKGROUND: The prognosis for malignant gliomas remains dismal. We addressed the safety, feasibility and preliminary clinical activity of the vaccinations using autologous glioma cells and interleukin (IL)-4 gene transfected fibroblasts. METHODS: In University of Pittsburgh Cancer Institute (UPCI) protocol 95-033, adult participants with recurrent glioblastoma multiforme (GBM) or anaplastic astrocytoma (AA) received gross total resection (GTR) of the recurrent tumors, followed by two vaccinations with autologous fibroblasts retrovirally transfected with TFG-IL4-Neo-TK vector admixed with irradiated autologous glioma cells. In UPCI 99-111, adult participants with newly diagnosed GBM or AA, following GTR and radiation therapy, received two intradermal vaccinations with the TFG-IL4-Neo-TK-transfected fibroblasts admixed with type-1 dendritic cells (DC) loaded with autologous tumor lysate. The participants were evaluated for occurrence of adverse events, immune response, and clinical response by radiological imaging. RESULTS AND DISCUSSION: In UPCI 95-033, only 2 of 6 participants received the vaccinations. Four other participants were withdrawn from the trial because of tumor progression prior to production of the cellular vaccine. However, both participants who received two vaccinations demonstrated encouraging immunological and clinical responses. Biopsies from the local vaccine sites from one participant displayed IL-4 dose-dependent infiltration of CD4+ as well as CD8+ T cells. Interferon (IFN)-gamma Enzyme-Linked Immuno-SPOT (ELISPOT) assay in another human leukocyte antigen (HLA)-A2+ participant demonstrated systemic T-cell responses against an HLA-A2-restricted glioma-associated antigen (GAA) epitope EphA2883-891. Moreover, both participants demonstrated clinical and radiological improvement with no evidence of allergic encephalitis, although both participants eventually succumbed with the tumor recurrence. In 99-111, 5 of 6 enrolled participants received scheduled vaccinations with no incidence of major adverse events. Monocyte-derived DCs produced high levels of IL-12 p70. Treatment was well tolerated; however, we were unable to observe detectable IFN-gamma post-vaccine responses or prolonged progression-free survival in these participants. CONCLUSION: Feasibility challenges inherent in the generation of a patient-specific gene transfection-based vaccine strongly suggests the need for more practical formulations that would allow for the timely administration of vaccines. Nevertheless, successful generation of type-1 DCs and preliminary safety in the current study provide a strong rationale for further efforts to develop novel glioma vaccines.

Safety and efficacy of the porcine small intestinal submucosa dural substitute: results of a prospective multicenter study and literature review.

OBJECT: Dural substitutes are often needed after neurosurgical procedures to expand or replace dura mater resected during surgery. A new dural repair material derived from porcine small intestinal submucosa (SIS) was evaluated in a prospective multicenter clinical study. METHODS: Between 2000 and 2003, 59 patients at five different institutions underwent dural reconstruction with the SIS dural substitute, with a minimum follow up of 6 months. The primary goals of the study were to assess the efficacy and safety of the SIS dural substitute according to the rate of cerebrospinal fluid (CSF) leakage, infection, and meningitis. Chiari malformation Type I decompression (32 patients) and tumor resection (18 patients) were the most common procedures performed, with 81% of SIS grafts implanted in the posterior fossa or spine. There was one case of a CSF leak (1.7%), two cases of wound infection (3.4%), and no cases of bacterial meningitis (0%) in the 58 patients available for follow up. In both cases of wound infection, the SIS graft acted as a barrier to infection and was not removed. Intraoperatively, a watertight seal was achieved in all 59 cases. On follow-up imaging available in 27 patients there was no evidence of any adverse reaction to the graft or of cerebral inflammation. CONCLUSIONS: The SIS dural substitute demonstrated substantial efficacy in these patients after a mean follow up of 7.3 +/- 2.2 months. Rates of infection, CSF leakage, and meningitis were comparable to those reported for other dural substitute materials. A lack of adverse reactions to the graft, favorable safety profile, and clinical efficacy all point to the utility of this material as an alternative for dural repair.

Human Immunodeficiency Virus-associated primary effusion lymphoma: An exceedingly rare entity in cerebrospinal fluid.

Primary effusion lymphoma (PEL) in patients with Human Immunodeficiency Virus (HIV) infection may involve pleural, pericardial, and peritoneal cavities. PEL involving the cerebrospinal fluid (CSF) is exceedingly rare, and to our knowledge has only been reported in two cases. We report another case of PEL diagnosed in CSF from a 61-year-old male with Acquired Immunodeficiency Syndrome that presented with neurological symptoms. Imaging studies of his brain showed leptomeningeal/periventricular enhancement, but no mass lesion. His CSF demonstrated human herpesvirus-8 positive pleomorphic lymphoplasmacytoid cells of null cell phenotype. This case highlights that albeit rare, PEL should be included in the differential diagnosis when large atypical cells are encountered in CSF of HIV-positive patients, even when such patients have no history of lymphoma. As in this case, ancillary studies are required to make an accurate diagnosis of PEL in CSF cytology.

Visual field deficit caused by vascular compression from a suprasellar meningioma: case report.

OBJECTIVE AND IMPORTANCE: Suprasellar meningiomas typically cause bitemporal hemianopsia by direct compression of the chiasm, its blood supply, or both. We report another mechanism for visual loss in suprasellar meningiomas, whereby compression by the suprajacent vascular complex is the offending agent. CLINICAL PRESENTATION: A 78-year-old woman with a suprasellar meningioma was diagnosed incidentally. During the follow-up period, she developed an inferior homonymous wedge defect consistent with superior compression, without any detectable radiological progression. It was decided to resect her tumor. INTERVENTION: The patient underwent a fronto-orbital approach for tumoral excision. Intraoperatively, a groove by the anterior cerebral artery complex was found along the superior surface of the chiasm. Postoperatively, the patient's visual deficit resolved. CONCLUSION: This case illustrates an unusual visual field deficit associated with a suprasellar meningioma. It also emphasizes the importance of frequent and careful visual field monitoring, which can precede radiological and symptomatic progression.

Intracranial Rosai-Dorfman disease treated with microsurgical resection and stereotactic radiosurgery. Case report.

Sinus histiocytosis or Rosai-Dorfman disease (RDD) is a rare idiopathic histioproliferative disorder typically characterized by painless cervical lymphadenopathy, fever, and weight loss. Extranodal, intracranial disease is uncommon. In this report the authors describe the first case of intracranial RDD treated with stereotactic radiosurgery after resection. This 52-year-old man with known RDD presented with a 7-day course of fever, headache, diplopia, left facial paresthesias, and difficulty swallowing. No cranial nerve deficits were evident on examination, but right submandibular and inguinal node enlargements were noted. On neuroimaging, the patient was found to have a homogeneously contrast-enhancing petroclival lesion with extension into the left cavernous sinus. The patient underwent a combined left petrosal craniotomy and partial labyrinthectomy with duraplasty for biopsy sampling and partial microsurgical resection of the lesion. Microscopic examination of the biopsy specimen revealed the presence of a mixed cellular population with predominant mature histiocytes consistent with RDD. The residual tumor was treated with stereotactic radiosurgery 2 months after resection. On follow-up imaging the lesion had regressed significantly, with only slight dural enhancement remaining. Microsurgical resection for histological diagnosis, followed by stereotactic radiosurgery for residual tumor represents one treatment alternative in the management of intracranial RDD in which a complete resection carries the potential for excess morbidity.

Association of the Adult Chiari Malformation and Idiopathic Intracranial Hypertension: more than a coincidence.

There are significant similarities between the Adult Chiari Malformation (ACM) and Idiopathic Intracranial Hypertension (IIH). They include similar demographics, clinical presentation, and response to treatment. There is an eightfold increase in the incidence of significant tonsillar herniation in patients with IIH. Based on these findings and our observation in a subgroup of patients with failed ACM decompression, we suggest that these disorders are interrelated in a group of patients. The physiopathology is that of craniocephalic disproportion, i.e., a disproportion between the skull and the brain, due to a small skull or posterior fossa (like in ACM) and/or an engorged brain (like in IIH). This will occasionally lead to tonsillar ectopia. The craniocephalic disproportion will alter the brain compliance and lead to the symptomatology.

Cesarean delivery in a parturient with syringomyelia and worsening neurological symptoms.

A parturient presented at 35 weeks' gestation with worsening neurological symptoms caused by syringomyelia. She underwent urgent cesarean delivery. The etiology and anesthetic considerations for an obstetrical patient with syringomyelia are discussed.

Pneumocephalus after resection of a lung cancer with posterior chest wall involvement.

Pneumocephalus after resection of intrathoracic tumors is an extremely rare event. A delayed presentation of iatrogenic subarachnoid pleural fistula resulted in symptomatic pneumocephalus after resection of a locally recurrent T4N0 nonsmall cell lung cancer involving the chest wall, T2 to T4 rib heads, and intercostal vertebral foramina. Progressive neurologic decline was noted 3 weeks after discharge. Computed tomography of the head and chest confirmed the presence of an apical pleural space, thoracic subarachnoid air, and pneumocephalus. Immediate clinical improvement followed chest tube decompression of the pleural space.

Rehabilitation and medical management of the adult with spina bifida.

.As the life expectancy of individuals with spina bifida increases, a lifelong need for management of many health issues in a rehabilitation setting has emerged in recent years. Physiatrists, in consultation with a variety of adult specialists, are particularly well suited to manage the common musculoskeletal, skin, bowel, bladder, renal, neurological, and other issues that arise in the adult population. This article reviews the last 20 yrs of literature pertinent to the rehabilitative care of this population, summarizes current evidence-based practice, and identifies key areas in which scientific evidence is lacking and future research is needed.