A case of complete clearance of chronic subdural hematoma accompanied by recurrent glioblastoma multiforme after administration of bevacizumab.

The efficacy of bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), as an adjuvant therapy against various malignant tumors was recently established. Its pharmacological effects in malignant tumors, including gliomas, were speculated to involve neovascularization inhibition and vascular permeability. Recently, it has been reported that the outer membrane of chronic subdural hematoma (CSDH) contains high levels of VEGF, which were implicated in neovascularization of the outer membrane. Furthermore, studies suggested that VEGF has the etiology in CSDH development, although its involvement is not fully understood. Here, we report the first case of chronic subdural hematoma that was improved by bevacizumab administration for recurrent glioblastoma. The present case could contribute to the hypothesis that VEGF may be associated with CSDH. We also discuss the pathogenesis and mechanism of CSDH recurrence from the viewpoint of VEGF function.

Synergistic antitumor effect with indoleamine 2,3-dioxygenase inhibition and temozolomide in a murine glioma model.

OBJECT Indoleamine 2,3-dioxygenase (IDO), a key enzyme of tryptophan (Trp) metabolism, is involved in tumor-derived immune suppression through depletion of Trp and accumulation of the metabolite kynurenine, resulting in inactivation of natural killer cells and generation of regulatory T cells (Tregs). It has been reported that high expression of IDO in cancer cells is associated with suppression of the antitumor immune response and is consistent with a poor prognosis. Thus, IDO may be a therapeutic target for malignant cancer. The authors have recently shown that IDO expression is markedly increased in human glioblastoma and secondary glioblastoma with malignant change, suggesting that IDO targeting may also have therapeutic potential for patients with glioma. The aim of this study was to investigate the antitumor effect of IDO inhibition and to examine the synergistic function of IDO inhibitor and temozolomide (TMZ) in a murine glioma model. METHODS Murine glioma GL261 cells and human glioma U87 cells were included in this study. The authors used 3 mouse models to study glioma cell growth: 1) a subcutaneous ectopic model, 2) a syngeneic intracranial orthotopic model, and 3) an allogenic intracranial orthotopic model. IDO inhibition was achieved via knockdown of IDO in GL261 cells using short hairpin RNA (shRNA) and through oral administration of the IDO inhibitor, 1-methyl-l-tryptophan (1-MT). Tumor volume in the subcutaneous model and survival time in the intracranial model were evaluated. RESULTS In the subcutaneous model, oral administration of 1-MT significantly suppressed tumor growth, and synergistic antitumor effects of 1-MT and TMZ were observed (p < 0.01). Mice containing intracranially inoculated IDO knockdown cells had a significantly longer survival period as compared with control mice (p < 0.01). CONCLUSIONS These results suggest that IDO expression is implicated in immunosuppression and tumor progression in glioma cells. Therefore, combining IDO inhibition with standard TMZ treatment could be an encouraging therapeutic strategy for patients with malignant glioma.

Expression of indoleamine 2,3-dioxygenase and correlation with pathological malignancy in gliomas.

BACKGROUND: : Indoleamine 2,3-dioxygenase (IDO) is a tryptophan catabolic enzyme involved in immune tolerance and tumor immune escape processes. Recently, IDO expression has been found to correlate with the prognosis of malignant tumors, but the implication of IDO in glioma progression remains unknown. OBJECTIVE: : To investigate the relationship between IDO expression and histological malignancy in gliomas. METHODS: : IDO expression was examined in a total of 75 surgical specimens obtained from 68 patients with glioma using immunohistochemical staining. The 75 specimens included 15 diffuse astrocytomas, 21 anaplastic astrocytomas, and 39 glioblastomas. Six of 39 glioblastomas were secondary glioblastomas, transforming from grade II or III gliomas that had been determined at the first surgery. IDO expression rate was compared in each histological grade, and patient survival was analyzed. RESULTS: : Expression of IDO was found in 72 of 75 gliomas at varying intensities. Stronger expression of IDO was more likely to be observed in malignant gliomas compared with low-grade gliomas. IDO expression in the 6 cases of secondary glioblastoma was stronger than in the initial low-grade glioma. Survival analysis using the Kaplan-Meier method revealed that grade IV patients with strong IDO expression had significantly worse overall survival rates (P = .04) than patients with weak IDO expression. CONCLUSION: : IDO is expressed more strongly in both primary and secondary glioblastoma tissue than low-grade glioma and may affect clinical outcome. If IDO promotes glioma cells to escape from the immune system, IDO may be a crucial therapeutic target for malignant gliomas.

Diagnostic value of the optic nerve sheath subarachnoid space in patients with intracranial hypotension syndrome.

OBJECT: The size of the subarachnoid space in the optic nerve sheath (ONS) on MR images is thought to reflect intracranial pressure. The diagnostic value of this space was investigated in patients with spontaneous intracranial hypotension (SIH) syndrome. METHODS: Coronal fat-saturated T2-weighted MRI of the orbit was performed in 15 patients with SIH fulfilling the diagnostic criteria for headache caused by low CSF pressure of the International Classification of Headache Disorders or the criteria for spontaneous spinal CSF leaks and intracranial hypotension. The size of the subarachnoid space in the ONS was measured in 2 slices behind the eyeballs. The images were compared before and after treatment. The CSF pressure was measured by lumbar puncture. RESULTS: Before treatment, the diameter of the ONS subarachnoid space ranged from 2.58 to 4.21 mm (mean 3.34 mm) and the thickness from 0 to 0.48 mm (mean 0.15 mm). Both measurements showed significant correlations with CSF opening pressure, and 8 patients had no CSF space before treatment. The size of CSF space increased in many patients after effective treatment. CONCLUSIONS: Disappearance of the CSF space in the ONS was frequently observed in patients with SIH. This characteristic finding may be useful in the diagnosis of SIH as well as in the evaluation of treatment effectiveness.

Tethered cord syndrome in identical twins.

The diagnosis of tethered cord syndrome (TCS) without typical conus medullaris symptoms and the radiological features such as a low set conus medullaris or dysraphic malformation is difficult. We report 11 year old identical twin brothers with TCS associated with the conus at the normal level. Their presenting symptom was progressive leg pain and both patients underwent surgical interruption of the filum terminale. The pain recurred in one patient treated surgically only after symptom became worse but resolved immediately in the other sibling treated promptly. We indicate the importance of early diagnosis and treatment of TCS to obtain excellent long-term outcome despite the absence of a low set conus or specific symptoms. Furthermore, when a twin or sibling of an affected person has neurological symptoms and the cutaneous signature of spinal dysraphism, radiological examination should be performed to establish the cause.

Patulous Eustachian tube in spontaneous intracranial hypotension syndrome.

A 48-year-old slender woman presented with a rare case of spontaneous intracranial hypotension syndrome manifesting as patulous Eustachian tube. The patient complained of sudden onset of ear fullness and nasal voice as well as typical orthostatic headache. Patulous Eustachian tube was identified by observation of synchronous movement of the tympanic membrane with respiration and swallowing. The diagnosis of spontaneous intracranial hypotension was confirmed by negative cerebrospinal fluid pressure, and typical magnetic resonance imaging and radioisotope cisternography findings. All symptoms completely resolved within a few days after epidural blood patch treatment. Changes in the venous blood distribution led by collapse of the dural sac of the cervical spine in the standing position presumably caused decreased size of the pterygoid venous plexus around the Eustachian tube.