Effectiveness of radiation therapy on brain invasion by human papillomavirus-related multiphenotypic sinonasal carcinoma: A case report.

Human papillomavirus (HPV)-related multiphenotypic sinonasal carcinoma (HMSC) is newly suggested and characterized by HPV-related tumors. HMSC has a relatively good prognosis. No cases of brain invasion have been reported to date. We encountered a case of brain invasion by HMSC, in which we assessed the effectiveness of radiotherapy in comparison with biopsy and autopsy. A 69-year-old man was referred to a hospital three months after intracerebral hemorrhage (ICH). Contrast magnetic resonance imaging revealed a tumor in the ethmoid sinus involving the brain. We performed transnasal biopsy and intensity-modulated radiotherapy for sinonasal and intracranial lesions. Despite radiotherapy, the patient died on day 41 after radiation. Biopsy specimens displayed mixed findings of epithelial and mesenchymal components. The tumor was immunoreactive for p16, and the RNA in situ hybridization for HPV was positive. Finally, we diagnosed the patient as having HMSC. Autopsy of the sinonasal tissue revealed a reduction in the number of tumor cells. There was a marked reduction in the number of tumor cells in the sinonasal tissue compared to that in the invaded brain tissue. The effectiveness of radiotherapy could depend on the histopathological components and location of the lesion, even in the same patient.

Feasibility of Mechanical Thrombectomy for Acute Ischemic Stroke Patients Aged 90 Years or Older Compared to Younger Patients.

Mechanical thrombectomy (MT) is a proven treatment for acute ischemic stroke (AIS). However, the efficacy of this treatment is uncertain for very elderly patients. This study aimed to investigate the safety and effectiveness of MT in 90 years or older patients compared with younger patients. We retrospectively reviewed AIS patients treated with MT between October 2018 and June 2020 in our institution. Patients were divided into two groups: aged ≥90 and <90 years. We compared the following factors: functional outcome at discharge, in-hospital death, successful recanalization, and complications. Multivariate logistic regression analysis for the good functional outcome was performed. In consideration of pre-stroke basic activities of very elderly patients, we defined the good functional outcome as modified Rankin Scale (mRS) 0-3. In all, 66 patients were included, and 19 patients (28%) were ≥90 years old. Pre-stoke mRS was higher in ≥90-year-old patients (p = 0.01). In ≥90-year-old patients, we achieved successful recanalization in 17 patients (90%), and only one patient experienced hemorrhagic complication related with the procedure. The good functional outcome (mRS: 0-3) at discharge were six patients (32%) in ≥90 years old versus 19 patients (40%) in <90 years old (p = 0.6). Three patients died in hospital in each group (16% versus 6%) (p = 0.3). Only the stroke severity was negatively related with the good functional outcome in a multivariate analysis. In conclusion, for ≥90-year-old patients compared with younger patients, MT is an equally feasible therapy. Patients should not be excluded from MT based on age alone.

Additional seizure reduction by replacement with Vagus Nerve Stimulation Model 106 (AspireSR).

AspireSR is a novel vagus nerve stimulation (VNS) device which detects ictal heart rate changes and automatically apply additional stimulus. We investigated the difference of the efficacy between AspireSR and preceding VNS models in patients with device replacement. We retrospectively reviewed the clinical data of 17 patients whose VNS devices were changed because of battery discharge. The rates of seizure reduction, the number of antiepileptic drugs (AEDs) used and device parameters between the two devices were evaluated. AspireSR improved significantly the rates of seizure reduction of the patients. Four patients out of 11 patients with low response to the preceding VNS models (no change or <50 % reduction) achieved>50 % seizure reduction. The AEDs used were not different in the observed periods. The device parameters were low setting in AspireSR compared to preceding VNS models. AspireSR decrease significantly seizure frequencies compared to the preceding VNS models. Change of the devices to AspireSR at the time of battery empty could be recommendable.

Anaplastic changes of diffuse leptomeningeal glioneuronal tumor with polar spongioblastoma pattern.

Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a rare glioneuronal neoplasm with oligodendroglioma-like cells confined in the subarachnoid spaces. A great majority of DLGNT are histologically low grade. However, some tumors show features of anaplasia with increased mitotic and proliferative activity. Due to the limited number of patients and inadequate clinical follow-up reported to date, the WHO classification does not yet assign a distinct WHO grade to this entity. Polar spongioblastoma pattern, in which bipolar cells are arranged in parallel with palisading nuclei, remains poorly understood about the pathological process of forming this pattern. We experienced a case of 22-year-old man developing DLGNT with extensively distributed anaplastic changes involving polar spongioblastoma pattern and the secondary tumor invasion to brain parenchyma in 4½ years before the autopsy. Clinical and pathological courses of the patient are presented with radiological, histopathological, and genetic examinations. This is the first report demonstrating the immunohistological and genetic evaluation of a DLGNT with polar spongioblastoma pattern.

Genetically Engineered Multilineage-Differentiating Stress-Enduring Cells as Cellular Vehicles against Malignant Gliomas.

Malignant glioma, the most common malignant brain tumor in adults, is difficult to treat due to its aggressive invasive nature. Enzyme/prodrug suicide gene therapy based on the herpes simplex virus thymidine kinase (HSVtk)/ganciclovir (GCV) system is an efficient strategy for treating malignant gliomas. In the present study, we evaluated treatment with multilineage-differentiating stress-enduring (Muse) cells, which are endogenous non-tumorigenic pluripotent-like stem cells that are easily collectable from the bone marrow as SSEA-3+ cells, as carriers of the HSVtk gene. Human Muse cells showed potent migratory activity toward glioma cells both in vitro and in vivo. HSVtk gene-transduced Muse cells (Muse-tk cells) at a cell number of only 1/32 that of U87 human glioma cells completely eradicated U87 gliomas in nude mouse brains, showing a robust in vivo bystander effect. Pre-existing intracranial U87 gliomas in nude mouse brains injected intratumorally with Muse-tk cells followed by intraperitoneal GCV administration were significantly reduced in size within 2 weeks, and 4 of 10 treated mice survived over 200 days. These findings suggest that intratumoral Muse-tk cell injection followed by systemic GCV administration is safe and effective and that allogeneic Muse-tk cell-medicated suicide gene therapy for malignant glioma is clinically feasible.

The efficacy of resection of an intradural extramedullary foramen magnum cavernous malformation presenting with repeated subarachnoid hemorrhage: a case report.

BACKGROUND: Intradural extramedullary cavernous angiomas of the central nervous system are a rare type of cavernous angioma, but they can cause fatal subarachnoid hemorrhage. The efficacy of resection for this type of cavernous malformations remains uncertain. This is the first report to recommend surgical resection of these types of lesions regardless of the fatal condition. CASE PRESENTATION: Our patient was a 70-year-old Japanese man who experienced a sudden onset of an occipital headache, followed by bilateral abducens nerve palsy. Magnetic resonance imaging revealed a small amount of hemorrhage in both of the lateral ventricles and an intradural extramedullary mass lesion in the left side of his foramen magnum. Two weeks after the appearance of initial symptoms, he became comatose. A computed tomography scan showed an increase in the subarachnoid intraventricular hemorrhaging and of the acute hydrocephalus. Following ventricular drainage, total tumor resection was performed using the lateral suboccipital transcondylar approach in conjunction with a first cervical hemilaminectomy. We observed a grape-like vascular-rich tumor with calcification that was adhering tightly to the wall of his left vertebral artery. A histopathological examination of the surgery specimen identified it as a cavernous angioma. After placement of a ventriculoperitoneal shunt and 2 months of rehabilitation, he recovered completely. CONCLUSIONS: An intradural extramedullary foramen magnum cavernous malformation is quite rare. The fragile surface of our patient's lesion was causing repeated subarachnoid hemorrhage and consequently progressive fatal neurological deterioration. Surgical resection of the lesion to prevent repeated hemorrhage was performed and he recovered fully. Therefore, we recommend surgical resection of the lesion regardless of the potentially fatal condition.

Supratentorial subdural hematoma following microvascular decompression: a report of four cases.

INTRODUCTION: Microvascular decompression has become an accepted surgical technique for the treatment of trigeminal neuralgia, hemifacial spasm, and other cranial nerve rhizopathies. However, critical complications still exist, and postoperative hemorrhage is one of the most life threatening complications following microvascular decompression. Most of the hemorrhages occur in the infratentorial region, and we found only four reports of supratentorial acute hemorrhages following microvascular decompression. Here, we report four cases of such hematomas and discuss the potential underlying mechanisms. Moreover, we discuss methods for handling such complications. CASE DESCRIPTION: Between 2004 and 2015, four patients developed postoperative hemorrhages, all of which were supratentorial subdural hematomas. The hematomas occurred ipsilaterally in two cases and contralaterally in two cases. All of the patients were treated conservatively and discharged without clinical symptoms. DISCUSSION AND EVALUATION: Although several intracranial hematomas have been reported distant from the craniotomy site, few reports of remote subdural hematomas after microvascular decompression exist. Draining large amounts of intraoperative cerebrospinal fluid may induce brain shifts and tearing of the small bridging veins. Of our four cases, two were ipsilateral and two were contralateral, and the side of the hemorrhage may suggest possible mechanisms of remote subdural hematomas in microvascular decompression. Although a lateral position for microvascular decompression mainly extends ipsilateral bridging veins, a postoperative supine position can extend bilateral veins equally. Therefore, we assumed that, supratentorial subdural hematomas occurred when the patients were returned to the supine position at the end of the microvascular decompression surgery. We may be able to prevent supratentorial subdural hematomas with the application of sufficient amounts of artificial cerebrospinal fluid immediately after a microvascular decompression. CONCLUSION: We suggest that it is important to avoid excessive CSF aspiration and to compensate for the cerebrospinal fluid loss with artificial cerebrospinal fluid adequately in order to avoid subdural hematomas after microvascular decompression. In addition, immediate postoperative CT scan is recommended even if the MVD has performed uneventfully.

Use of genetically engineered stem cells for glioma therapy.

Glioblastoma, the most common and most malignant type of primary brain tumor, is associated with poor prognosis, even when treated using combined therapies, including surgery followed by concomitant radiotherapy with temozolomide-based chemotherapy. The invasive nature of this type of tumor is a major reason underlying treatment failure. The tumor-tropic ability of neural and mesenchymal stem cells offers an alternative therapeutic approach, where these cells may be used as vehicles for the invasion of tumors. Stem cell-based therapy is particularly attractive due to its tumor selectivity, meaning that the stem cells are able to target tumor cells without harming healthy brain tissue, as well as the extensive tumor tropism of stem cells when delivering anti-tumor substances, even to distant tumor microsatellites. Stem cells have previously been used to deliver cytokine genes, suicide genes and oncolytic viruses. The present review will summarize current trends in experimental studies of stem cell-based gene therapy against gliomas, and discuss the potential concerns for translating these promising strategies into clinical use.

Interferon-ß and temozolomide combination therapy for temozolomide monotherapy-refractory malignant gliomas.

Interferon-ß (IFN-ß) has been found to downregulate O6-methyl-guanine-DNA methyltransferase and sensitize glioma cells to chemoradiation therapy. The effectiveness of IFN-ß and temozolomide (TMZ) combination therapy for newly diagnosed glioblastomas was previously reported. However, there is no clinical report of recurrent of malignant gliomas treated with the combination of IFN-ß and TMZ. In the present study, we reported 7 cases of gliomas classified as uncontrollable with adjuvant TMZ monotherapy, who were then treated with IFN-ß and TMZ combination therapy. The magnetic resonance imaging findings and clinical symptoms improved in the majority of the cases, with tolerable adverse events and minimal residual disability. The overall survival (OS) time from the date of the initial surgery exceeded 13 months, suggesting that this combination therapy was successful in improving the prognosis of malignant gliomas refractory to adjuvant TMZ monotherapy.

Pseudo-continuous arterial spin labeling reflects vascular density and differentiates angiomatous meningiomas from non-angiomatous meningiomas.

Pseudo-continuous arterial spin labeling (PCASL) can measure tumor blood flow (TBF) reliably. We investigated meningioma TBF using PCASL and assessed for any correlation with histopathological microvascular density (MVD) and the World Health Organization (WHO) classification. Conventional MRI with contrast T1-weighted images and PCASL were acquired with a 3 T scanner before surgery in 25 consecutive patients with meningiomas. Using the PCASL perfusion map, the mean and maximum TBF were calculated from regions of interest placed in the largest cross-sectional plane of each tumor. Tissue sections from 16 patients were stained with CD31 to evaluate MVD and were assigned a WHO classification. The TBFs were statistically compared with MVD and the histopathological meningioma subtypes. There were 16 meningothelial meningiomas, four angiomatous meningiomas, two fibrous meningiomas, one transitional meningioma, and two atypical meningiomas. We observed significant correlation between MVD and both mean and maximum TBF (p < 0.05). The mean and maximum TBF ((mean)TBF, (max)TBF) in angiomatous meningiomas are significantly higher than that in non-angiomatous meningiomas (p < 0.05). PCASL is useful in assessing meningioma vascularity, and in differentiating angiomatous meningiomas from non-angiomatous meningiomas.

Effect of boron neutron capture therapy for recurrent anaplastic meningioma: an autopsy case report.

A 70-year-old woman died of systemic metastasis from anaplastic meningioma and underwent autopsy. The patient underwent twice total removal of the right sphenoid ridge meningioma 2 years ago. The tumor recurred 3 times, and then stereotactic radiotherapy was employed. Boron neutron capture therapy (BNCT) was performed for the fourth local recurrence and an additional new lesion. Proliferative activity of the newly developed meningioma, which had been treated with BNCT only, was significantly lower than that of untreated metastatic liver tumor, as well as that of the meningioma specimen obtained at the second surgery. Our pathological findings demonstrated, for the first time, the therapeutic effect of BNCT on anaplastic meningioma at an early stage (2.5 months).

Extraventricular neurocytoma of the sellar region with spinal dissemination.

Extraventricular neurocytoma (EVN) is a rare tumor that mainly occurs in the cerebral hemispheres and spinal cord. Sellar neurocytoma is extremely rare, with only two previously reported cases. We report a sellar EVN in a 48-year-old man presenting with visual impairment. This tumor was partially resected. The residual tumor disappeared on MRI with adjuvant radiotherapy. However, 2 years later the tumor recurred with craniospinal dissemination, which is also very rare, with only four previously reported cases. The recurrent tumor showed atypical features with an MIB-1 LI score of 3 %. It is suggested that postoperative adjuvant radiation therapy with long-term follow-up is required for incompletely resected EVN.

Dissecting Aneurysm at the Proximal Segment of the Anterior Cerebral Artery Associated with Infraoptic Course Anterior Cerebral Artery.

A 48-year-old man presented a subarachnoid hemorrhage caused by a rupture of a dissecting aneurysm at the proximal segment (A1 segment) of the right anterior cerebral artery (ACA). He also had an anomalous artery named infraoptic course ACA and an agenesis of the contralateral ACA A1 segment. Balloon occlusion test at the bifurcation of the right internal carotid artery demonstrated that the distal segments of the bilateral ACAs were perfused through the infraoptic course ACA. Therefore, we surgically trapped the A1 segment including the aneurysm. The patient got discharged without any neurological deficit. Natural course of ACA dissecting aneurysms is unclear because of rarity of the disease and treatment strategy is still controversial. Most of the dissecting aneurysms in the A1 segment are surgically treated, because they often present with massive hemorrhage and poor prognosis. In the present case, the contralateral A1 segment was absent but trapping of the dissecting aneurysm could be achieved without vascular reconstruction (e.g., bypass surgery) because of the presence of the infraoptic course ACA.

Evaluation of tumor blood flow after feeder embolization in meningiomas by arterial spin-labeling perfusion magnetic resonance imaging.

Preoperative embolization changes the amount of blood flow and pattern of flow distribution in meningioma. Tumor blood flow was investigated in eight meningioma patients before and after embolization using arterial spin-labeling (ASL) perfusion imaging. Although blood flow was significantly reduced in the whole tumor after embolization, changes in flow distribution patterns varied from one case to another. The findings suggest that evaluation of post-embolization tumor blood flow by ASL perfusion imaging would be useful in the surgical planning of meningioma.

Intraosseous schwannoma of the cervical vertebral body: A case report and review of the literature.

Intraosseous schwannomas (IOS) of non-sacral vertebra are extremely rare; only 14 cases were reported previously. We described a case of IOS involving a cervical vertebral body, successfully treated by surgical resection, with a review of the literature and discussion of this extremely rare tumour.