Glioma surgery represents a significant advance with respect to improving resection rates using new surgical techniques, including intraoperative functional mapping, monitoring, and imaging. Functional mapping under awake craniotomy can be used to detect individual eloquent tissues of speech and/or motor functions in order to prevent unexpected deficits and promote extensive resection. In addition, monitoring the patient’s neurological findings during resection is also very useful for maximizing the removal rate and minimizing deficits by alarming that the touched area is close to eloquent regions and fibers. Assessing several types of evoked potentials, including motor evoked potentials (MEPs), sensory evoked potentials (SEPs) and visual evoked potentials (VEPs), is also helpful for performing surgical monitoring in patients under general anesthesia (GA). We herein review the utility of intraoperative mapping and monitoring the assessment of neurological findings, with a particular focus on speech and the motor function, in patients undergoing glioma surgery.
Meningiomas are the most common intracranial primary neoplasm in adults. Although the spectrum of clinical and molecular genetic issues regarding meningiomas remains undefined, novel genetic alterations that are associated with tumor morphology, malignancy, or location have recently been discovered. This review focuses on recent advances in understanding of the heterogenous pathology of meningiomas, particularly on associations between the clinical, histological, etiological, epidemiological, and molecular genetical aspects of the neoplasm.
The current World Health Organization (WHO) classification of tumors of the central nervous system (CNS) is essentially a lineage-oriented classification based on a presumable developmental tree of CNS. A four-tiered WHO grading scheme has been successfully applied to a spectrum of diffusely infiltrative astrocytomas, but it is not fully applicable to other gliomas, including oligodendrogliomas and ependymomas. Recent genetic studies have revealed that the major categories of gliomas, such as circumscribe astrocytomas, infiltrating astrocytomas/oligodendrogliomas, and glioblastoma, roughly correspond to major genetic alterations, including isocitrate dehydrogenases (IDHs) 1/2 mutations, TP53 mutations, co-deletion of chromosome arms 1p/19q, and BRAF mutation/fusion. These genetic alterations are clinically significant in terms of the response to treatment(s) and/or the prognosis. It is, thus, rational that future classification of gliomas should be based on genotypes, rather than phenotypes, although the genetic features of each tumor are not sufficiently understood at present to draw a complete map of the gliomas, and genetic testing is not yet available worldwide, particularly in Asian and African countries. This review summarizes the current concepts of the WHO classification, as well as the current understanding of the major genetic alterations in glioma and the potential use of these alterations as diagnostic criteria.
Glioblastoma (GBM) has proven to be incurable despite recent progress on its standard of care using temozolomide (TMZ) as the main trunk of initial therapy for newly diagnosed GBM. One of the main reasons accounting for the dismal prognosis is attributed to lack of active therapeutic regimens at recurrence. Since TMZ is the most active cytotoxic agent against GBM, and the standard dosing of TMZ has shown favorable safety profile in clinical trials, re-challenge with TMZ in increased dose density schedules for recurrent tumors that have evaded from prior standard TMZ therapy appears to be a rational approach and has been intensively exploited. A number of phase II clinical trials using different alternating scheduling of dose-dense TMZ (ddTMZ) have shown superior efficacy over the standard TMZ or historical controls with other alkylating agents including nitrosoureas and procarbazine. One ddTMZ schedule, consisting of a 21-days on/7-days off regimen was applied to newly-diagnosed GBM as the adjuvant monotherapy after completion of combined radiation and TMZ and failed to demonstrate survival benefit in a large phase III trial (RTOG 0525). Thus its role in TMZ-pretreated, recurrent GBM should be carefully pursuit in randomized trials, e.g., planned JCOG 1308 trial comparing a 7-days on/7-days off ddTMZ regimen used upfront at the first relapse followed by bevacizumab on progression versus bevacizumab alone, investigating whether insertion of ddTMZ prior to bevacizumab could bestow better outcome in the recurrent setting. In this article, mode of action, past trials, and future directions of ddTMZ therapy are discussed.
New radiation modalities have made it possible to prolong the survival of individuals with malignant brain tumors, but symptomatic radiation necrosis becomes a serious problem that can negatively affect a patient’s quality of life through severe and lifelong effects. Here we review the relevant literature and introduce our original concept of the pathophysiology of brain radiation necrosis following the treatment of brain, head, and neck tumors. Regarding the pathophysiology of radiation necrosis, we introduce two major hypotheses: glial cell damage or vascular damage. For the differential diagnosis of radiation necrosis and tumor recurrence, we focus on the role of positron emission tomography. Finally, in accord with our hypothesis regarding the pathophysiology, we describe the promising effects of the anti-vascular endothelial growth factor antibody bevacizumab on symptomatic radiation necrosis in the brain.
Cancer stem cells (CSCs) are the sole population possessing high self-renewal activity in tumors, with their existence affecting tumor recurrence. However, the invasive activity of CSCs has yet to be fully understood. In this article, we established a tumor sphere culture of RSV-M mouse glioma cells (RSV-M-TS) and evaluated their migration and invasion activities. Histological analysis of a tumor formed by cranial injection of the RSV-M-TS cells showed highly invasive properties and similarities with human malignant glioma tissues. When the migration activity of both RSV-M and RSV-M-TS cells were compared by intracranial injection, rapid migration of RSV-M-TS cells was observed. To confirm the invasive capabilities of RSV-M-TS cells, a three-dimensional collagen invasion assay was performed in vitro using RSV-M, RSV-M-TS, and RSV-M-TS cells cultured with medium containing serum. RSV-M and RSV-M-TS cultured with medium containing serum for 8 days indicated low migration activity, while moderate invasion activity was observed in RSV-M-TS cells. This activity was further enhanced by incubation with medium containing serum overnight. To identify the genes involved in this invasion activity, we performed quantitative polymerase chain reaction (PCR) array analysis of RSV-M and RSV-M-TS cells. Of 84 cancer metastasis-related genes, up-regulation was observed in 24 genes, while 4 genes appeared to be down-regulated in RSV-M-TS cells. These results suggest that the enhanced invasive activity of glioma sphere cells correlates with a number of tumor metastasis-related genes and plays a role in the dissemination and invasion of glioma cells.
The vidian canal (VC), a bony tunnel in which the vidian artery and nerve pass, has been widely known as an important landmark to identify the anterior genu of the petrous carotid artery (AGPCA) especially during lateral extended endoscopic endonasal approachs (LEEEAs). The objectives of this study in the Japanese population are to describe the radiological anatomic features and relationships between VC and its surrounding structures, and discuss the clinical implications. We studied 231 high-resolution computed tomography (CT) scans with a slice thickness of 0.5 mm. All the patients had known sellar or parasellar pathologies but without any involvement of VC. The following VC-related parameters were examined: its length, relationship to AGPCA, course from the pterygopalatine fossa to the carotid canal, its position relative to the medial pterygoid plate and pneumatization pattern of the sphenoid sinus. Mean length of VC is 14.6 mm. There is more tendency of straight-running VC compared to other populations. VC locates infero-lateral to AGPCA in all the cases. The protrusion of VC and the paraclival carotid artery to the sphenoid sinus, as well as well-pneumatization of the sinus is also observed more frequently in almost a half of the population. Surgeons who perform LEEEAs in Japanese patients must know these anatomical features. The characteristics particular to Japanese populations may facilitate better identification of VC and exposure to AGPCA intraoperatively.
Global cerebral ischemia and reperfusion (I/R) often result in high mortality. Free radicals play an important role in global cerebral I/R. Xanthine oxidoreductase (XOR) inhibitors, such as allopurinol, have been reported to protect tissues from damage caused by reactive oxygen species (ROS) by inhibiting its production through XOR inhibition. The recently introduced XOR inhibitor febuxostat, which is a more potent inhibitor than allopurinol, is expected to decrease free radical production more effectively. Here, we analyzed the effects of allopurinol and febuxostat in decreasing global severe cerebral I/R damage in mice. Mice were divided into three groups: a placebo group, an allopurinol group, and a febuxostat group. Pathological examinations, which were performed in each group in the CA1 and CA2 regions of the hippocampus 4 days after I/R surgery, revealed that there was a decrease in the number of neuronal cells in the 14-min occlusion model in both regions and that drugs that were administered to prevent this damage were not effective. The enzymatic activity was extremely low in the mouse brain, and XOR could not be detected in the nonischemic and ischemic mice brains with western blot analyses. Thus, one of the reasons for the decreased effectiveness of XOR inhibitors in controlling severe whole-brain ischemia in a mouse model was the low levels of expression of XOR in the mouse brain.
We report the case of a 58-year-old woman with low-grade astrocytoma, who developed massive intracranial hemorrhage as the first presentation of this disease, and become comatose and subsequently underwent an emergency craniotomy. A small amount of tumor-like tissue was observed on the wall of the hematoma cavity. Histological analysis of the resected specimen indicated diffuse astrocytoma [World Health Organization (WHO) grade II]. The patient was discharged without neurological deficits 2 weeks after the operation. A non-enhanced tumor-like nodule was observed on magnetic resonance imaging 3 months after the operation, which was monitored carefully but was not treated by adjuvant therapy. The tumor grew gradually, and a second operation was performed 3 years after the first, in which the tumor was completely resected. Histological analysis of the resected specimen again indicated diffuse astrocytoma (WHO grade II). Although rare, brain tumors, including low-grade astrocytoma, should be considered a possible cause of subcortical hemorrhage in patients without risk factors for intracranial hemorrhage.
Superficial siderosis is a rare condition caused by hemosiderin deposits in the central nervous system (CNS) due to prolonged or recurrent low-grade bleeding into the cerebrospinal fluid (CSF). CNS tumor could be one of the sources of bleeding, both pre- and postoperatively. We report an extremely rare case of superficial siderosis associated with purely third ventricle craniopharyngioma, and review previously reported cases of superficial siderosis associated with CNS tumor. A 69-year-old man presented with headache, unsteady gait, blurred vision, and progressive hearing loss. Brain magnetic resonance (MR) imaging with gadolinium revealed a well enhanced, intraventricular mass in the anterior part of the third ventricle. T2*-weighted gradient echo (GE) MR imaging revealed a hypointense rim around the brain particularly marked within the depth of the sulci. Superficial siderosis was diagnosed based on these findings. The tumor was diffusely hypointense on T2*-weighted GE imaging, indicating intratumoral hemorrhage. The lateral ventricles were dilated, suggesting hydrocephalus. [18F]fluorodeoxyglucose positron emission tomography revealed increased uptake in the tumor. The whole brain surface appeared dark ocher at surgery. Histological examination showed the hemorrhagic tumor was papillary craniopharyngioma. His hearing loss progressed after removal of the tumor. T2*-weighted GE MR imaging demonstrated not only superficial siderosis but also diffuse intratumoral hemorrhage in the tumor. Superficial siderosis and its related symptoms, including hearing loss, should be considered in patients with hemorrhagic tumor related to the CSF space. Purely third ventricle craniopharyngioma rarely has hemorrhagic character, which could cause superficial siderosis and progressive hearing loss.
An 84-year-old male with a 3-month history of headache and elevated C-reactive protein levels was admitted for biopsy of the superficial temporal artery, which led to the diagnosis of giant cell arteritis (GCA). Two days after prednisolone therapy was initiated, the patient began to experience transient vertigo attacks. Two days later, dysarthria, left-sided hemiparesis, right abducens palsy, and horizontal nystagmus developed. Magnetic resonance (MR) imaging disclosed fresh infarctions in the vertebrobasilar territory. Since the patient became drowsy because of brainstem compression and hydrocephalus due to cerebellar swelling, emergency suboccipital decompression surgery and ventricular drainage were performed. Subsequently, the patient’s consciousness levels improved. MR angiography revealed right vertebral artery (VA) occlusion and left VA stenosis due to arteritis. Ischemic stroke is a serious though relatively rare complication of GCA. Similar cases have been reported, in which ischemic stroke developed despite or possibly due to steroid therapy. To our knowledge, this is the first description of vertebrobasilar infarction associated with GCA in the Japanese population. The merits and potential demerits of steroid therapy are briefly discussed.
Marfan syndrome can demonstrate tortuous and elongated intracranial arteries. However, these arteries rarely cause neurovascular compression resulting in hemifacial spasm or trigeminal neuralgia. Theauthors report a 33-year-old woman who was diagnosed as Marfan syndrome, suffered from trigeminalneuralgia. Magnetic resonance (MR) angiography showed tortuous and elongated left vertebral artery (VA). The coronal section of three dimensional (3D) MR cisternography with contrast enhancement showed that the left trigeminal nerve was compressed from underneath by the tortuous and elongated left VA. After successful surgery of microvascular decompression, the patient’s symptom resolved and no recurrence was encountered. Neurosurgeons should not only be aware of hemifacial spasm but also of trigeminal neuralgia caused by elongated vessels in a patient with Marfan syndrome, although it is an extremely rare condition. In addition, offending vessel is not atherosclerotic in younger patients unlike usual cases of trigeminal neuralgia. Thus, microvascular decompression can be easier than usual cases. Care should be taken to prevent arterial dissection during transposition by using some technical tips.