Perifosine, a Bioavailable Alkylphospholipid Akt Inhibitor, Exhibits Antitumor Activity in Murine Models of Cancer Brain Metastasis Through Favorable Tumor Exposure.

Metastatic brain tumors are regarded as the most advanced stage of certain types of cancer; however, chemotherapy has played a limited role in the treatment of brain metastases. Here, we established murine models of brain metastasis using cell lines derived from human brain metastatic tumors, and aimed to explore the antitumor efficacy of perifosine, an orally active allosteric Akt inhibitor. We evaluated the effectiveness of perifosine by using it as a single agent in ectopic and orthotopic models created by injecting the DU 145 and NCI-H1915 cell lines into mice. Initially, the injected cells formed distant multifocal lesions in the brains of NCI-H1915 mice, making surgical resection impractical in clinical settings. We determined that perifosine could distribute into the brain and remain localized in that region for a long period. Perifosine significantly prolonged the survival of DU 145 and NCI-H1915 orthotopic brain tumor mice; additionally, complete tumor regression was observed in the NCI-H1915 model. Perifosine also elicited much stronger antitumor responses against subcutaneous NCI-H1915 growth; a similar trend of sensitivity to perifosine was also observed in the orthotopic models. Moreover, the degree of suppression of NCI-H1915 tumor growth was associated with long-term exposure to a high level of perifosine at the tumor site and the resultant blockage of the PI3K/Akt signaling pathway, a decrease in tumor cell proliferation, and increased apoptosis. The results presented here provide a promising approach for the future treatment of patients with metastatic brain cancers and emphasize the importance of enriching a patient population that has a higher probability of responding to perifosine.

Successful treatment of a case of tentorial dural arteriovenous fistula causing subarachnoid hemorrhage with invagination of the brainstem by huge and multiple venous pouches.

BACKGROUND: We present a case of tentorial dural arteriovenous fistula (TDAVF) causing subarachnoid hemorrhage with mass effect of large venous pouches, which was struggling to diagnosis and management due to complex vasculature and severe general condition. CASE DESCRIPTION: A 43-year-old man was transferred to our hospital due to sudden consciousness disturbance. A neurological examination revealed tetraparesis and pupil dilatation with no light reflex. Imaging findings showed a large lesion in the brainstem with subarachnoid and intraventricular hemorrhage. Since there were multiple feeding arteries and large and multiple venous pouches on vascular imaging, we diagnosed the patient with TDAVF. Because of a high-flow arteriovenous shunt and the presence of large venous pouches, it appeared to be very difficult to approach the shunting point by direct surgery. Therefore, we first performed transarterial endovascular treatment with 25% n-butyl-2-cyanoacrylate to shrink the venous pouches and to reduce the pressure of the posterior fossa, followed by direct radical interruption of the shunting point using the craniotomy maneuver. Postoperative vascular imaging revealed disappearance of abnormal feeding arteries, draining veins, and venous pouches. The patient was discharged and transferred to a rehabilitation hospital with a modified Rankin Scale Score of 3. Accurate interpretation of the detailed vasculature preoperatively and an appropriate treatment strategy using endovascular and direct surgical technique are required to achieve a satisfactory outcome for difficult-to-treat dural arteriovenous fistulas. CONCLUSIONS: This combined maneuver with endovascular embolism as complementary pretreatment for radical surgery is useful for a case with high-flow shunting and large venous pouches.

A surgical strategy using a fusion image constructed from 11C-methionine PET, 18F-FDG-PET and MRI for glioma with no or minimum contrast enhancement.

The objective of this study was to investigate the distribution of 11C-methionine (MET) and F-18 fluorodeoxyglucose (FDG) uptake in positron emission tomography (PET) imaging and the hyperintense area in T2 weighted imaging (T2WI) in glioma with no or poor gadolinium enhancement in magnetic resonance imaging (GdMRI). Cases were also analyzed pathologically. We prospectively investigated 16 patients with non- or minimally enhancing (< 10% volume) glioma. All patients underwent MET-PET and FDG-PET scans preoperatively. After delineating the tumor based on MET uptake, integrated 3D images from FDG-PET and MRI (GdMRI, T2WI or FLAIR) were generated and the final resection plane was planned. This resection plane was determined intraoperatively using the navigation-guided fencepost method. The delineation obtained by MET-PET imaging was larger than that with GdMRI in all cases with an enhanced effect. In contrast, the T2WI-abnormal signal area (T2WI+) tended to be larger than the MET uptake area (MET+). Tumor resection was > 95% in the non-eloquent area in 4/5 cases (80%), whereas 10 of 11 cases (90.9%) had partial resection in the eloquent area. In a case including the language area, 92% resection was achieved based on the MET-uptake area, in contrast to T2WI-based partial resection (65%), because the T2WI+/MET- area defined the language area. Pathological findings showed that the T2WI+/MET+ area is glioma, whereas 6 of 9 T2WI+/MET- lesions included normal tissues. Tissue from T2W1+/MET+/FDG+/GdMRI+ lesions gave an accurate diagnosis of grade in six cases. Non- or minimally enhancing gliomas were classified as having a MET uptake area that totally or partially overlapped with the T2WI hyperintense area. Resection planning with or without a metabolically active area in non- or minimally enhancing gliomas may be useful for accurate diagnosis, malignancy grading, and particularly for eloquent area although further study is needed to analyze the T2WI+/MET- area.

[Diagnosis of Cochleovestibular Neurovascular Compression Syndrome:A Scoring System Based on Five Clinical Characteristics].

The optimal method for diagnosing cochleovestibular neurovascular compression syndrome(CNVC)remains controversial, and the aim of this study is to develop a standard diagnostic instrument for the condition. The clinical features of 53 sides of 50 patients with a combination of vertigo, tinnitus, and/or hearing loss were retrospectively evaluated. The following five clinical features were evaluated and given a score of 1 or 0:1)a long history of recurrent vertigo, tinnitus, or hearing loss;2)neurological findings related to positional vertigo, nystagmus, tinnitus, or hearing loss;3)neuro-otological findings involving tinnitus, audiometry, or vestibular testing;4)auditory brainstem response(ABR)evaluation with the detection of a low 25-75% II wave amplitude on the contralateral side and delayed interpeak latency in the I-III or I-V waves(usually low II wave amplitude combined with double peaks and a wide-based form)during ABR evaluation using 80 and 90dB clicks;and 5)the detection of vascular contact with the eighth cranial nerve on magnetic resonance imaging-constructive interference in steady state or air computed tomography imaging. Finally, the sum of these scores was evaluated. For cases in which more than one of the features of the items 1), 2), or 3) were present, the score was evaluated based on the most representative of the items. RESULTS: The patients were divided into those with scores of 4-5 and those with scores of 2-3. All the patients with scores of 4-5 exhibited CNVC, while those with scores of 2-3 had other diseases. Therefore, CNVC should be suspected in patients with scores of 4-5, but can be ruled out in those with scores of 2-3.

Metastatic cerebellar tumor of papillary thyroid carcinoma mimicking cerebellar hemangioblastoma.

INTRODUCTION: Well-differentiated papillary thyroid carcinoma generally (PTC) have a favorable prognosis. This metastasis is rare in the central nervous system. Brain metastasis has a relatively poor prognosis. We present a rare case of cerebellar metastasis, one that mimics a solid type cerebellar hemangioblastoma and because of which it was very hard to reach accurate preoperative diagnosis. Accurate diagnosis was challenging because of the similar imaging and histopathological findings for these two tumors. CASE DESCRIPTION: A brain lesion was detected by routine medical checkup of the brain with MRI in a 49-year-old woman 2 years after thyroidectomy for well-differentiated PTC. Gadolinium-enhanced MRI showed a homogeneous prominently enhanced lesion with surrounding enhanced dilated vessels in the left cerebellar hemisphere. Digital subtraction angiography showed a strongly stained lesion fed by the peripheral branch of the left posterior inferior cerebellar artery with drainage into the inferior vermian vein, revealing arteriovenous shunting. The most like likely preoperative diagnosis was felt to be that of a solid cerebellar hemangioblastoma. Gross total resection of the tumor was achieved by bilateral suboccipital craniotomy, and intraoperative pathological analysis suggested hemangioblastoma. Histopathological findings showed proliferation of vacuolated sheeted tumor cells with clear and eosinophilic cytoplasm and numerous thin-walled microvessels, consistent with hemangioblastoma. However, the final diagnosis was brain metastasis of the follicular variant of PTC due to a partial thyroid follicle-like pattern including eosinophilic fluid pathologically and positive TTF-1 immunostaining. DISCUSSION AND EVALUATION: Since presented rare case of cerebellar metastasis of PTC was very similar to solid type cerebellar hemangioblastoma on imaging and histopathological findings, accurate diagnosis was challenging. Moreover, it is extremely rare for a cerebellar metastasis to occur as an initial distant metastasis of PTC, and hemangioblastoma is the most common primary cerebellar neoplasm in adults. This epidemiological data was also one of the reason of difficulty to reach preoperative accurate diagnosis. CONCLUSIONS: To the best of our knowledge, there are no other reports of challenging diagnosis case of these two tumors in the literature. Brain metastasis of a well-differentiated PTC could be a relatively poor prognostic factor, and accurate diagnosis and suitable surgical therapy or radiotherapy are needed.

A proposal for standardized analysis of the results of microvascular decompression for trigeminal neuralgia and hemifacial spasm.

BACKGROUND: The purpose of this study was to evaluate and analyze overall postoperative results from microvascular decompression (MVD) by combining the cure rate of symptoms with the complication rate. A new scoring system for obtaining objective surgical results from MVD for trigeminal neuralgia (TN) and hemifacial spasm (HFS) is proposed to document treatment results using consistent criteria in a standardized manner. METHOD: Surgical results combining complications , if any, were obtained from a questionnaire sent to patients who had undergone surgery for TN or HFS in recent years and had been followed-up for more than 1 year after surgery (TN patients, n = 54; HFS patients, n = 81) When surgical outcome is complete resolution of symptoms, the efficacy of surgery (E) is designated E-0, but when moderate symptoms are still persist postoperatively, the score is designated E-2. When no complications are seen after surgery, the complication score (C) is C-0, while the score is C-2 if troublesome complications remain. In addition, total evaluation of the results (T) is judged by combining the E and C scores. For example, when E is 0, and C is C-2, the total evaluation is scored as T-2, which is diagnosed as fair. FINDINGS: The response rate of the questionnaire was 80.7% (109/135). Overall surgical data were evaluated and analyzed using our new scoring system. Analysis of the collected data revealed an outcome of T-0 was 70% (35/50 patients) and T-1 was 24% (12/50) and T-2 was 6% (3/50) in TN, whereas in HFS, T-0 was 61% (36/59) and T-1 was 27.1% (16/59) and T-2 was 6.8% (4/59) and T-3 was 5.1% (3/59). CONCLUSION: The total results of MVD should be evaluated and analyzed by combining the cure rate of symptoms together with the complication rate. This new scoring system could allow much more objective analysis of the results of following MVD. Adopting this scoring system to objectively judge treatment results for TN and HFS, individual surgeons can compare their own overall surgical results with those of other institutes. Comparative results of MVD can also be provided to patients considering therapy to allow informed decision-making on the basis of good quality evidence.

Cerebellopontine angle facial schwannoma relapsing towards middle cranial fossa.

Facial nerve schwannomas involving posterior and middle fossas are quite rare. Here, we report an unusual case of cerebellopontine angle facial schwannoma that involved the middle cranial fossa, two years after the first operation. A 53-year-old woman presented with a 3-year history of a progressive left side hearing loss and 6-month history of a left facial spasm and palsy. Magnetic resonance imaging (MRI) revealed 4.5 cm diameter of left cerebellopontine angle and small middle fossa tumor. The tumor was subtotally removed via a suboccipital retrosigmoid approach. The tumor relapsed towards middle cranial fossa within a two-year period. By subtemporal approach with zygomatic arch osteotomy, the tumor was subtotally removed except that in the petrous bone involving the facial nerve. In both surgical procedures, intraoperative monitoring identified the facial nerve, resulting in preserved facial function. The tumor in the present case arose from broad segment of facial nerve encompassing cerebellopontine angle, meatus, geniculate/labyrinthine and possibly great petrosal nerve, in view of variable symptoms. Preservation of anatomic continuity of the facial nerve should be attempted, and the staged operation via retrosigmoid and middle fossa approaches using intraoperative facial monitoring, may result in preservation of the facial nerve.

Successful neuroendoscopic treatment of intraventricular brain abscess rupture.

Intraventricular rupture of a brain abscess is still associated with a high mortality rate. Here, we report such a case in a patient with normal immunity that was treated successfully using neuroendoscopic approach. A 69-year-old man who had presented with headache and fever developed confusion and restlessness. Magnetic resonance imaging revealed a mass with ring enhancement extending to the right ventricle. Emergency aspiration of cerebrospinal fluid (CSF) from the spinal canal revealed severe purulent meningitis. Bacterial culture of the CSF and blood was negative. Because of prolonged consciousness disturbance, the patient underwent evacuation of the intraventrcular abscess using a neuroendoscope. The pus was centrifuged and collected for bacterial culture, and this revealed Streptococcus intermedius/milleri. After implantation of a ventricular catheter, gentamicin sulfate was administered twice a day for 9 days. Cefotaxime sodium was also administered intravenously for 14 days, followed by oral administration of cefcapene pivoxil hydrochloride for 10 days. The patient made a complete recovery, and was discharged 31 days after admission. After 20 months of follow-up, he is doing well and has returned to his work. In cases of intraventricular rupture of a brain abscess, a neuroendoscopic approach is useful for evacuation of intraventricular debris or septum, and identification of the causative bacterium for selection of antibiotics, possibly reducing the period of hospitalization.

Occipital inter-hemispheric approach for lateral ventricular trigone meningioma.

OBJECTIVE: The optimal surgical approach for a trigone meningioma is still controversial. Here, we report two patients with trigone meningioma treated successfully via an occipital inter-hemispheric and trans-cortical approach in the lateral semi-prone position. CLINICAL PRESENTATION: A 53-year-old woman was admitted to a local hospital with sudden transient dizziness and vomiting. The CT brain scan demonstrated a right intra-ventricular tumour. She was therefore transferred to our hospital for surgical treatment. The other patient was a 67-year-old woman who was admitted to a local hospital after a traffic accident and a CT brain scan revealed an incidental right intra-ventricular tumour. After referral to our hospital, periodic MRI examinations revealed gradual tumour enlargement within a one-year period. Neither of the patients had any neurological deficits, including in the visual fields. INTERVENTION: The head of each patient was positioned so that the tumour-containing right ventricle was oriented downwards and laterally. An occipital inter-hemispheric approach was performed and using a navigation system, the tumour was identified about 1 cm in depth from the cortical surface. After the medial part of the tumour was debulked, the posterior and then the anterior choroidal blood supplies to the tumour were identified. Occlusion of these vessels achieved tumour haemostasis. The tumours were totally removed via a 1.5-cm cortical incision. Brain retraction was minimal because the right hemisphere was pulled down by gravity. Therefore, the para-splenial cisterns were easily accessed, resulting in early release of cerebrospinal fluid. Post-operative MRI showed complete removal of the tumour and the patients had no neurological deficits. Anti-epileptic medication was withdrawn one week after the operation. CONCLUSIONS: The occipital inter-hemispheric fissure lacks important bridging veins. The approach used and patient positioning minimized damage to the lateral aspect of the optic radiation and the corpus callosum. Except in patients with very large trigone meningiomas, this approach is useful for decreasing the risk of post-operative hemianopsia or epilepsy, and possibly speech disturbance, even in patients with a tumour in the dominant hemisphere.

Ruptured internal carotid artery anterior wall aneurysm identified during vasospasm: case report.

OBJECTIVE AND IMPORTANCE: Aneurysms of the paraclinoid segment arising from the anterolateral wall of the proximal internal carotid artery (ICA) are usually located in the intradural space, and the proximal neck of the aneurysm is closely adjacent to the dural ring. Although most of these aneurysms can be identified by cerebral angiography, the top of the aneurysm can be flattened because of its relationship to the undersurface of the clinoid process. We report a rare case of a ruptured ICA anterolateral wall aneurysm that was not identified by initial angiography but was clearly observed at the time of vasospasm. CLINICAL PRESENTATION: A 59-year-old female patient was transferred to our hospital because of sudden loss of consciousness. Initial angiography failed to disclose any aneurysm except for one projecting to the right at the C3-C4 portion of the left ICA. A left frontotemporal craniotomy with drilling of the anterior clinoid process was performed 1 day after the onset of subarachnoid hemorrhage. Within the operative field, however, no hemorrhage was detected near the C3-C4 portion of the left ICA. Subsequent angiography performed during vasospasm clearly demonstrated a ruptured aneurysm in the anterior paraclinoid segment of the right ICA. INTERVENTION: After drilling the anterior clinoid process and cutting the dural ring, we successfully clipped the aneurysm. The aneurysm was saccular, with a broad neck that extended below the dural ring. Intraoperative inspection demonstrated that the dome of the aneurysm was in a subclinoid location, suggesting that most of the aneurysm might have been flattened by the dural ring at the time of initial angiography but before the onset of vasospasm. CONCLUSION: The presented case suggests that this type of aneurysm may be missed by routine angiography performed before and after vasospasm. If initial angiography fails to reveal the origin of the subarachnoid hemorrhage but computed tomography still discloses hemorrhage from an ICA aneurysm, repeated angiography should be considered within 14 days after the onset of subarachnoid hemorrhage to confirm whether the aneurysm has arisen from the anterior clinoid segment of the ICA.