Katsuhiro Mizutani

Histopathological investigation of glioblastomas resected under bevacizumab treatment

To date, no clinical observations have been reported for histopathological changes in human gliomas under antiangiogenic treatment. We collected six glioblastomas resected under bevacizumab treatment. Histopathological investigation was performed by hematoxilyn-eosin staining and immunohistochemistry for CD34, VEGF, VEGFR1/2, HIF-1α, CA9, and nestin as compared to eleven control glioblastomas to assess the differences in histological features, microvessel density, expression of VEGF and its receptors, tumor oxygenation, and status of glioma stem-like cells. In the six tumors resected under bevacizumab, microvascular proliferation was absent, and microvessel density had significantly decreased compared with that of the controls. The expressions of VEGF and its receptors were downregulated in two cases of partial response. HIF-1α or CA9 expression was decreased in five of the six tumors, whereas the decreased expression of these markers was noted in only one of the 11 control glioblastomas. The expression of nestin significantly decreased in the six tumors compared with that of the controls, with the remaining nestin-positive cells being relatively concentrated around vessels. We provide the first clinicopathological evidence that antiangiogenic therapy induces the apparent normalization of vascular structure, decrease of microvessel density, and improvement of tumor oxygenation in glioblastomas. These in situ observations will help to optimize therapy.

Analysis of the intercavernous sinuses using multidetector computed tomography digital subtraction venography (CT-DSV)

PURPOSES The intercavernous sinuses (ICSs) connect both sides of the cavernous sinus. Knowledge of the ICSs is useful when employing the endoscopic endonasal transsphenoidal approach. Although there were some studies concerning the anatomy of ICSs using cadavers, there is no well-recognized method of the radiological evaluation of the ICSs. Therefore, we evaluate the ICSs using computed tomography digital subtraction venography (CT-DSV) in the cases of unruptured aneurysm that had the normal sellae anatomy. METHODS We retrospectively analyzed 97 cases of unruptured cerebral aneurysm that had normal parasellar and sellar anatomy except for the aneurysms. The analysis was performed using the multi-planar reconstruction images obtained by CT-DSV in these cases. RESULTS The anterior ICS (AICS), inferior ICS (IICS) and posterior ICS (PICS) were detected in 51 cases (52.6%), 28 cases (28.9%) and 76 cases (78.4%) respectively. In the cases older than 51 years old, the AICS was detected significantly less often than in those younger than 50 years old. CONCLUSIONS The CT-DSV images directly reflected the blood flow. Most of the past research on the ICSs was obtained using cadavers, which could therefore not directly assess the normal human blood flow. The present study showed the usefulness of CT-DSV for evaluating the ICSs and to understand the normal anatomy of the ICSs.

Thrombosis of the draining vein causes intracranial haemorrhage in the natural history of brain arteriovenous malformation: case report

Abstract Rupture of arteriovenous malformations (AVM) may be caused by venous outflow restriction, but there is no radiographic evidence of this. We report a case showing only a venous thrombus preceding intracranial haemorrhage from AVM. This is the first evidence that venous thrombus results in AVM rupture in its natural history.

The importance of amyloid β protein in cerebrospinal fluid when you recognize convexal subarachnoid hemorrhage.

Background: Convexal subarachnoid hemorrhage (cSAH) is sometimes experienced in cerebral amyloid angiopathy (CAA), but ones that are repeated within a brief time period are not common. Also, it is often difficult to diagnose CAA when you experience a case of cSAH. Methods: We examined the clinical course of 2 cases that showed cSAH repeatedly. We examined cerebrospinal fluid (CSF) concentrations of amyloid β protein (Aβ) 40 and 42 and tau protein as additional evidence for a diagnosis of CAA. Results: Case 1 presented with transient motor paresis of the left hand and case 2 with transient sensory disturbance of the left hand. CT scans showed cSAH on the right central sulcus in both patients. Case 1 showed development of intracerebral hemorrhage on the frontal lobe near the right central sulcus. Case 2 showed relapse of cSAH with recurrence of the same symptoms. These cases could not be diagnosed by image analysis, but were considered CAA by Aβ40, Aβ42 and tau protein in CSF. Conclusion: Aβ in CSF can be presented here as support for the diagnosis of CAA that is difficult to diagnose by Boston criteria.

The Analysis of the Petrosal Vein to Prevent Venous Complications During the Anterior Transpetrosal Approach in the Resection of Petroclival Meningioma

BACKGROUND The anterior transpetrosal approach (ATPA) has been used in the resection of petroclival meningioma (PCM) for more than 20 years. Although PCM sometimes involves the petrosal vein and its preservation has been an important issue, the precise risk of petrosal vein sacrifice and subsequent venous complications associated with the use of the ATPA in patients with PCM has not yet been elucidated. METHODS We used computed tomographic (CT) digital subtraction venography (DSV) in the retrospective analysis of the petrosal vein and its tributaries in patients with PCM before and after surgery. We also examined the incidence of postoperative venous complications in each of the patients. RESULTS The detection rate of the petrosal vein and some of its tributaries on CT-DSV in patients with PCM was significantly lower than that in controls. Preoperatively, CT-DSV detected the petrosal vein in 71.8% of patients with PCM. The detected petrosal veins were preserved after the operation in 64.3% of these patients. No venous complications involving petrosal vein were observed in any of the patients. Anastomosis between the petrosal vein and the basal vein via the pontotrigeminal vein was found to be significantly more developed in the patients with PCM compared with the controls. CONCLUSIONS Our study demonstrated that the ATPA could be performed safely on patients with PCM from the viewpoint of venous preservation. Preoperative CT-DSV is important for assessing the petrosal vein and its tributaries to facilitate a safer operation.

A case of papillary tumor of the pineal region with a long clinical history: molecular characterization and therapeutic consideration with review of the literature

A 37-year-old male patient initially visited another hospital at the age of 22 complaining of headache. At that hospital, magnetic resonance imaging (MRI) of his brain showed a heterogeneously enhancing mass with hydrocephalus in the pineal gland. The patient underwent ventriculo-peritoneal shunt placement with partial tumor resection of the mass, although pathologically, no definitive diagnosis was made regarding the tumor. At that time, he had left lower quadrantanopia and disturbances of extraocular movements (upward gaze palsy and limitation of lateral gaze). He was then followed as an outpatient at that hospital. When the patient was 31 years old, the headache returned and MRI scans of his brain revealed recurrence of the pineal tumor. He underwent two further operations via the occipital transtentorial approach. The pathological diagnosis was atypical choroid plexus papilloma. The patient then visited our hospital for a second opinion and further treatment (Fig. 1a). He first underwent a biopsy, and the diagnosis was pineal parenchymal tumor with intermediate differentiation (PPITD). He was administered two courses of chemotherapy with carboplatin and etoposide followed by focal irradiation (40 Gy in 20 fractions). However, the tumor was not very responsive to these treatments, and the patient underwent another operation for the residual tumor (partial removal) the following year; once again, the pathological diagnosis was PPTID. After the operation, he underwent intensity-modulated radiation therapy (IMRT) (30 Gy in 15 fractions). The residual tumor responded well to IMRT (partial response) (Fig. 1b, c), and the patient was followed as an outpatient. Five years after IMRT, MRI and positron emission tomography scans showed enlargement of the residual tumor (Fig. 1d, e). In addition, the patient’s symptoms were deteriorating, with progressive impairment of cognitive function and eye movement and an increase in gait disturbances. Therefore, he underwent another operation via high parietal approach. The tumor was only partially removed because of strong adhesion to the internal cerebral vein penetrating the tumor (Fig. 1f). This time, the pathological diagnosis was papillary tumor of the pineal region (PTPR). By this time, the patient could not walk due to weakness of extremities. He also suffered from cognitive deterioration and the majority of his time was spent in bed [Karnofsky performance status (KPS) 30]. Based on the reported similarities between PTPR and ependymoma, the presence of extensive perifocal edema and a few reports of success in the literature, the patient was treated with the combination chemotherapy of oral temozolomide (150 mg/m, days 1–5, 28-day cycle) and intravenous bevacizumab (7.5 mg/kg, day 0, every 4 weeks). The tumor showed a partial response to the combination therapy (Fig. 1g) and the patient’s symptoms began to gradually improve. To date, he has undergone a total of 16 courses of oral temozolomide and 18 courses of bevacizumab without any adverse events, and the treatment is still ongoing. The maximum response of the tumor was obtained after 6 courses of the combination chemotherapy, and the tumor volume has remained decreased for more than 14 months. Figure 1h shows the tumor 1 year after the initiation of the combination chemotherapy. The patient is & Hikaru Sasaki hsasaki@a5.keio.jp

Giant Cell Tumor of the Skull: Review of the Literature.

BACKGROUND Giant cell tumors (GCTs) are rare in the skull. The present report describes a case with a primary GCT located in the temporal bone and reviews the relevant literature. We also propose a treatment strategy for GCT of the skull. CLINICAL PRESENTATION A 41-year-old man presented with headache and auditory disturbance. Radiologic images showed a lytic expansive extradural lesion originating primarily from the right temporal bone and expanding into the middle cranial fossa and the infratemporal fossa. A biopsy specimen of the lesion was obtained from the external auditory meatus. Total removal was performed with temporal craniectomy, mandibular condylar process removal, tympanoplasty, and mastoidectomy. DISCUSSION The rate of recurrence of GCTs is related to complete resection and location of the GCT rather than to the degree of invasiveness. Some of the mononuclear cells and stromal cells in GCT express receptor activator of nuclear factor κ-β ligand (RANKL). Because inhibition of RANKL and bisphosphonate therapy might eliminate giant cells, this approach might be useful for recurrent or unresectable GCTs of the skull. CONCLUSIONS Preoperative diagnosis by biopsy is important in determining the therapeutic strategy of GCTs. Complete resection is important to reduce the recurrence rate of GCTs in the skull.

Intraosseous venous structures adjacent to the jugular tubercle associated with an anterior condylar dural arteriovenous fistula

PurposeAlthough involvement of the osseous component with an anterior condylar dural arteriovenous fistula (AC-DAVF) has been frequently described, osseous venous structures in which AC-DAVFs develop have not been fully elucidated. We investigated osseous venous structures adjacent to the hypoglossal canal in normal controls and patients with AC-DAVFs.MethodsThe study included 50 individuals with unruptured aneurysms as normal controls and seven patients with AC-DAVFs. Osseous venous structures adjacent to the hypoglossal canal in normal controls were analyzed using computed tomography (CT) digital subtraction venography. In patients with AC-DAVFs, the fistulous pouches, draining veins, and surrounding venous structures were examined using cone beam CT.ResultsIn 46.0% of laterals in normal controls, osseous venous structures were visualized within the jugular tubercle superomedially to the hypoglossal canal. We named these structures the jugular tubercle venous complex (JTVC). The JTVC was always continuous with the anterior condylar vein and was sometimes connected to surrounding venous channels. We detected nine fistulous pouches in the seven patients with AC-DAVFs. The fistulous pouches were in the JTVC (33.3%), anterior condylar vein (33.3%), and other venous channels within the exoccipital region (33.3%).ConclusionAlthough the JTVC is a venous structure frequently found in normal people, it had not been investigated until now. The venous channel between the anterior condylar vein and JTVC is a common origin site for AC-DAVFs, and it was associated with 66.6% of the AC-DAVF cases in the current study.

Analysis of the venous channel within the clivus using multidetector computed tomography digital subtraction venography

PurposeAlthough neuroradiologists and skull base neurosurgeons are aware of the existence of veins within the clivus, such vessels have seldom been described in the literature. The aim of the present study is to elucidate the detailed venous structure of the clivus.MethodsComputed tomography digital subtraction venography (CT-DSV) images of 50 unruptured aneurysm cases were examined retrospectively.ResultsEighteen emissary veins were identified in 14 (28.0%) cases. A half of the emissary veins connected the inferior petrosal sinus with the inferior petro-occipital vein (IPOV) in the middle clivus. The clival diploic vein (CDV) was identified in 14.0% of cases, 42.9% of which had the clivus of the presellar type. The CDV was connected to the posterior intercavernous sinus or the rostral end of the basilar plexus superiorly, and was connected to the IPOV, anterior condylar vein, marginal sinus, or the anterior condylar confluence.ConclusionThe CDV provides collateral channels between the cavernous sinus and the internal jugular vein and the inferior petrosal sinus and the IPOV. Understanding of the emissary veins in the clivus and the CDV is valuable for skull base surgery, especially for endonasal endoscopic skull base procedures.

Postnatal delayed exacerbation of dural sinus malformation associated with brainstem cavernous malformations: A case report

Dural sinus malformation (DSM) is a rare paediatric vascular malformation characterised by abnormal dilation of the posterior dural sinus. Owing to its rarity, the pathophysiology of DSM has not been fully elucidated. We report a case of prenatally diagnosed DSM with an unusual clinical course. We detected DSM in a male foetus in the 26th week of gestation by using foetal ultrasonography. Although the DSM regressed during the foetal stage and the arteriovenous shunt was insignificant in the neonate, the shunt rapidly developed four months after birth. The neonate also had postnatal de novo brainstem cavernous malformation (CM), which also developed rapidly, supposedly due to the aggravated venous hypertension resulting from the DSM. We successfully treated the aggravated shunts by endovascular transarterial and transvenous embolisation six times over two years and, subsequently, the clinical condition and the size of the brainstem CM became stable. The DSM and CM seemed to have a metameric origin. Such aberrant cases could help to further the understanding of DSM.