Ghassan K. Bejjani

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

BackgroundThe 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.MethodsIn 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 DiscussionIn 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 Four other participants were withdrawn from the trial because of tumor progression prior to production of the cellular vaccine.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)-γ 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-γ post-vaccine responses or prolonged progression-free survival in these participants.ConclusionFeasibility 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.

Vasospasm after cranial base tumor resection: pathogenesis, diagnosis, and therapy

OBJECTIVEnCerebral vasospasm is well known to occur after various cerebral neurosurgical events that cause subarachnoid hemorrhage. However, cerebral vasospasm can occur after cranial base tumor resection. We present a series of nine patients with angiographically evident vasospasm that was clinically symptomatic in eight of them.nnnMETHODSnA total of 470 consecutive patients with cranial base tumors were operated in our institution between April 1993 and December 1996. Nine had evidence of cerebral vasospasm postoperatively (1.9% of the total population), of whom eight were asymptomatic. There were seven males and two females with an age range of 33 to 65 years (average 48.5 years). There were seven meningiomas, one chordoma, and one trigeminal schwannoma.nnnRESULTSnVasospasm manifested clinically 1 to 30 days postoperatively in eight patients. Most patients were symptomatic within 7 days. In the ninth case, surgery was delayed when asymptomatic vasospasm was noted on an angiogram before second stage surgery. Symptoms included altered mental status in four patients, hemiparesis in three patients (one patient had both hemiparesis and altered mental status), and monoparesis in two patients. Factors that were found to correlate with a higher incidence of vasospasm were tumor size, total operative time, vessel encasement, vessel narrowing, and preoperative embolization. All eight patients with symptomatic vasospasm were treated with hypertensive, hypervolemic, hemodilutional (HHH) therapy. Five patients also underwent intraluminal angioplasty, in conjunction with papaverine in one case. One patient received intraarterial papaverine alone. Angiographic results were good in all patients. Significant clinical improvement was seen in six of the eight symptomatic cases.nnnCONCLUSIONnDelayed neurological deterioration in a patient who has undergone cranial base tumor surgery not explained by an intracranial mass lesion should be promptly investigated with angiography. If vasospasm is diagnosed, it should be treated aggressively with hypertensive, hypervolemic, hemodilutional therapy and early angioplasty.

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.

Treatment of failed Adult Chiari Malformation decompression with CSF drainage: observations in six patients

Summary.u2003Objective: We report the use of CSF drainage for the management of failed Adult Chiari Malformation (ACM) decompression.u2003Methods: All patients with more than one year follow-up after treatment of their failed ACM were included in this study. They underwent initial decompression between September 1998 and April 2000. Clinical and radiological data were collected initially and at recurrence. Lumbar punctures (LP) were done at recurrence for diagnostic and therapeutic purposes. Opening pressures and symptomatic relief were recorded. Therapeutic options included intermittent LP and ventriculo-peritoneal shunting (VPS).u2003Results: There were 6 patients (5 females and one male). Their age ranged from 19 to 43 years. Tonsillar descent ranged from 5 to 21 mm. The symptoms recurred 1.5 to 9 months postoperatively (average 5.6 months). Postoperative imaging revealed the presence of CSF flow behind the tonsils and the formation of a retrotonsillar neocistern in all patients. On LP, the opening pressure ranged from 17 to 31 cm of water (average 23 cm). All patients improved after CSF drainage, and four patients underwent VPS. The other patients were treated with repeat LP±Acetazolamide. There was significant improvement in all patients, with 18 months follow-up after CSF drainage (range 16–21 months).u2003Conclusion: Our results suggest a role for CSF drainage in the treatment of some patients with failed ACM surgery. Possible explanations for the failure of ACM surgery in this subgroup include: surgical complications leading to neural hydrodynamic alteration, inadequate initial surgery, and coexistence with another pathology, possibly a mild form of intracranial hypertension. More prospective and hydrodynamic studies are needed to further clarify these issues.

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

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.

Adult Chiari Malformation

Learning Objectives: After reading this article, the participant should be able to:1. Identify the epidemiologic and pathophysiologic aspects of adult Chiari malformation.2. Describe the clinical presentation and diagnostic workup of patients with adult Chiari malformation.3. Explain the indications for and complications of surgical treatment of adult Chiari malformation.

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.

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.

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.

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.