High HMGA2 expression without gene rearrangement in meningiomas.

High mobility group AT-hook 2 (HMGA2) is a non-histone transcriptional regulator protein. Aberrant expression of the HMGA2 gene (HMGA2) and structural rearrangement at the chromosomal region 12q14 with HMGA2 involvement have been reported in several mesenchymal tumors. We analyzed truncated and full-length HMGA2 expression in 55 cases of meningioma, the most common brain tumor of mesenchymal origin. Fluorescence in situ hybridization and 3'-rapid amplification of cDNA ends were used to investigate the possibility of gene rearrangements. Moreover, the relationship between HMGA2 expression and clinicopathological features was assessed. Compared with normal brain tissues, 95% of the meningioma tissues exhibited increased HMGA2 expression. In 14 cases, the expression of truncated HMGA2 was more than two-fold higher than that of paired full-length HMGA2. Chromosomal translocation involving the chromosomal region 12q14 was undetectable. No significant correlation was found between the Ki-67 labeling index and HMGA2 expression and between the HMGA2 expression and the clinicopathological features. The majority of the meningioma cases displayed increased HMGA2 expression, which was not attributed to the chromosomal rearrangement at the corresponding region. Similar to that in the other mesenchymal tumors, increased HMGA2 expression was not associated with tumor cell proliferation in meningiomas.

Increased Twist and ZEB2 expression in a cutaneous metastasis of high-grade glioma.

Extra-central nervous system metastasis of gliomas is extremely rare, and the biological mechanism underlying it remains poorly understood. Epithelial-to-mesenchymal transition (EMT) has received attention as one of the important processes of cancer metastasis. Here we describe the case of a 32-year-old man with cutaneous metastasis of high-grade glioma, together with the analysis of EMT-related molecules. Our patient presented with a high-grade glioma in the right frontal lobe. Cutaneous metastasis under the surgical scar developed 17 months after complete resection of the intracranial tumor. Histopathology of both the original and metastatic tumors revealed hypercellularity; the tumors predominantly comprised glial tumor cells with poor cellular processes. Immunohistochemical analysis demonstrated intense expression of nestin, focal expression of glial fibrillary acid protein, and absence of expression of oligodendrocyte transcription factor 2, endothelial membrane antigen, or neurofilament. Genetic analyses could not provide definitive diagnostic information of glioma subtypes. Immunohistochemical analysis for EMT-related biomarkers demonstrated increased Twist, zinc finger E-box-binding homeobox 2 (ZEB2), matrix metalloproteinase 2 (MMP2), and MMP9 expressions in tumor cells of the metastatic lesion compared with those of the primary lesion. Slug, E-cadherin, and N-cadherin expression were absent in both primary and metastatic lesions; however, ZEB1 expression was present in both. Our results suggest that Twist, ZEB2, MMP2, and MMP9 facilitate cutaneous metastasis of gliomas.

[Spontaneous Retroclival Subdural Hematoma Diagnosed Using Magnetic Resonance Imaging in an Adult Patient:A Case Report].

Spontaneous retroclival subdural hematoma is rare among adults. To the best of our knowledge, only six cases have been reported. A 73-year-old man presented with sudden severe headache, diplopia, and dysarthria, with no history of trauma. Head CT revealed a retrociliary hematoma. No obvious causes of bleeding, such as cerebral aneurysms or malformations, were detected. Conservative treatment was provided to the patient. MRI showed an intraventricular hemorrhage and a space between the basilar artery and hematoma three days after onset. The hematoma almost disappeared on day 7. MRI, particularly T2-weighted sagittal MRI, is effective in localizing hematomas and confirming intraventricular hemorrhages.

Convexity dural chondroma: a case report with pathological and molecular analysis.

Chondromas are rare benign tumors that commonly originate from the base of the skull, while those arising from the dura mater are less common. Although the molecular mechanism underlying its pathogenesis remains largely unknown, 12q13-15 rearrangements followed by the activation of HMGA2, which is associated with cell proliferation, have been reported in soft tissue chondromas. A recent comprehensive analysis of mesenchymal tumors identified an IDH1/2 mutation in cartilaginous tumors. However, these alterations have not yet been examined in dural chondromas. We here described clinical and pathological features in a new case of convexity dural chondroma with the wildtype IDH1/2 and expression of HMGA2 and reviewed the relevant literature.

Localized overexpression of alpha-internexin within nodules in multinodular and vacuolating neuronal tumors.

Multinodular and vacuolating neuronal tumors (MVNT) have been recently referred to as a distinctive neuronal tumor entity based on histopathological findings. They are characterized by multiple tumor nodules, vacuolar alteration and widespread immunolabeling for human neuronal protein HuC/HuD. Only 13 cases have been reported in the literature to date and little is known about the histopathology of these tumors. Herein, we report a case of MVNT with additional confirmation of immunohistochemical features. A 22-year-old woman presented with a continuous headache. MRI showed a subcortical white matter lesion with multiple satellite nodules in the frontal lobe appearing as T2/fluid-attenuated inversion recovery (FLAIR) hyperintensities. Histological examination of the resected lesion revealed well-defined multiple nodules composed of predominant vacuolating tumor cells. The tumor cells exhibited consistent immunolabeling for doublecortin, as well as HuC/HuD, both representative neuronal biomarkers associated with earlier stages of neuronal development. Immunopositivity for oligodendrocyte transcription factor 2 (Olig2) and S100 was also detected in tumor cells. Additionally, significant overexpression of alpha-internexin was observed in the background neuropil limited to tumor nodules. Neuronal nuclear antigen (NeuN), synaptophysin and neurofilament, markers for mature neurons, were either negative or weakly positive. The expression profile of neuronal biomarkers can be distinguished from that of classic neuronal tumors and is the immunohistochemical hallmark of MVNT. In summary, we identified the characteristic tumoral expression of HuC/HuD and doublecortin and the presence of abundant neuropil localized in MVNT tumor nodules, which exhibited widespread alpha-internexin expression. These results supported the presumption that MVNT is a distinct histopathological entity.

[A Case of Subgaleal Hematoma with Exophthalmos and Diplopia].

A 9-year-old girl struck the left side of her head on a doorknob, after which she gradually developed swelling. She was treated conservatively at another hospital before being referred and admitted to our hospital 9 days after injury, with complaints of exophthalmos and diplopia. Computed tomography (CT) scanning and magnetic resonance imaging (MRI) revealed a subgaleal hematoma (SGH). We therefore attempted to treat the patient by aspiration of the hematoma via needle puncture through the skin, for which we wrapped an elastic band around the head while infusing a hemostatic agent. No vascular anomalies and no abnormal shunts were identified by angiography under general anesthesia 13 days after injury. The patient was treated surgically due to increased head swelling and deteriorated exophthalmos. The liquefied, dark-red SGH was aspirated via a few cm of skin and a galeal incision on the left side of her head. A multiperforated drainage catheter was introduced into the hematoma cavity and the drainage catheter was connected to the vacuum-drain pump. After the surgery, the left exophthalmos disappeared. Twenty-three days after injury, she was discharged from our hospital without any neurological deficits.

Thromboembolic events associated with single balloon-, double balloon-, and stent-assisted coil embolization of asymptomatic unruptured cerebral aneurysms: evaluation with diffusion-weighted MR imaging.

INTRODUCTION: The introduction of the balloon remodeling and stent-assisted technique has revolutionized the approach to coil embolization for wide-neck aneurysms. The purpose of this study was to determine the frequency of thromboembolic events associated with single balloon-assisted, double balloon-assisted, and stent-assisted coil embolization for asymptomatic unruptured aneurysms. METHODS: A retrospective review was undertaken by 119 patients undergoing coiling with an adjunctive technique for unruptured saccular aneurysms (64 single balloon, 12 double balloon, 43 stent assisted). All underwent diffusion-weighted imaging (DWI) within 24 h after the procedure. RESULTS: DWI showed hyperintense lesions in 48 (40%) patients, and ten (21%) of these patients incurred neurological deterioration (permanent, two; transient, eight). Hyperintense lesions were detected significantly more often in procedures with the double balloon-assisted technique (7/12, 58%) than with the single balloon-assisted technique (16/64, 25%, p = 0.05). Occurrence of new lesions was significantly higher with the use of stent-assisted technique (25/43, 58%) than with the single balloon-assisted technique (p = 0.001). Symptomatic ischemic rates were similar between the three groups. The increased number of microcatheters was significantly related to the DWI abnormalities (two microcatheters, 15/63 (23.8%); three microcatheters, 20/41 (48.8%) (p = 0.008); four microcatheters, 12/15 (80%) (p = 0.001)). CONCLUSION: Thromboembolic events detected on DWI related to coil embolization for unruptured aneurysms are relatively common, especially in association with the double balloon-assisted and stent-assisted techniques. Furthermore, the number of microcatheters is highly correlated with DWI abnormalities. The high rate of thromboembolic events suggests the need for evaluation of platelet reactivity and the addition or change of antiplatelet agents.

[A case of glioblastoma multiforme in the pineal region with intraventricular hemorrhage].

INTRODUCTION: Glioblastoma multiforme (GBM) is a very rare type of tumor involving the pineal region. No case of pineal region GBM with tumoral hemorrhage has ever been reported. Here, we present the first such case report. CASE REPORT: A 65-year-old man presented with sudden-onset disturbance of consciousness. CT revealed intraventricular hemorrhage and acute hydrocephalus. The patient was treated by an emergent operation for ventricular drainage. MRI with contrast media showed a heterogeneous enhanced area in the pineal region. The patient underwent endoscopic biopsy surgery and a third ventriculostomy for non-communicating hydrocephalus. The pathological diagnosis was high-grade glioma, indicating the need for tumor removal via the occipital transtentorial approach. The tumor was removed subtotally and radiation and chemotherapy courses were then started. CONCLUSION: Pineal GBM with tumoral hemorrhage has never been reported before. Endoscopic operations are useful for rapid decision making prior to radical surgery.

A case of cribriform plate dural arteriovenous fistulas with a rare complication after endovascular therapy.

Background: Cribriform plate dural arteriovenous fistulas (dAVFs) are rarely encountered. Here, we report a case of cribriform plate dAVF with a rare complication after endovascular therapy. Case Description: A 60-year-old man presented with severe sudden headache. Head computed tomography showed right subdural hematoma, and magnetic resonance angiography showed dilated bilateral frontal cortical vein. Digital subtraction angiography revealed cribriform plate dAVF fed by the anterior and posterior ethmoidal branches of the bilateral ophthalmic arteries. Transarterial embolization with liquid embolic material was performed and the fistula disappeared. Although magnetic resonance imaging showed the disappearance of the cribriform plate dAVF and subdural hematoma, the patient complained of anosmia after the procedure. Conclusion: Endovascular embolization is an effective treatment option for treating cribriform plate dAVFs. However, anosmia is a possible complication, and endovascular surgeons should take care of this complication, especially in cribriform plate dAVFs supplied with blood bilaterally.

Skull shape abnormalities in ischemic cerebrovascular and mental diseases in adults.

Morphological changes in the child skull due to mechanical and metabolic stimulation and synostosis of the suture are well known. On the other hand, few studies have focused on clinical conditions relevant for adult skull deformity. We retrospectively reviewed computed tomography (CT) findings obtained from 365 cases that were treated for head injuries, moyamoya disease, cervical internal carotid artery stenosis, and mental diseases, and investigated the morphological changes in the skull associated with these diseases. The findings from head injuries were used not only for control subjects, but also for the analysis of generational changes in skull shape based on birth year. Head shape had a brachiocephalic tendency with occipital flattening in people born from the 1950s onwards. Cases of moyamoya disease, cervical internal carotid artery stenosis, and mental diseases showed significantly thicker frontal and occipital bone than those of control subjects. The skull thickening was especially noticeable in the frontal bone in moyamoya disease. Plagiocephaly was significantly frequent in moyamoya disease. These uncommon skull shapes are useful CT findings in screening subjects for early evidence of mental diseases and intracranial ischemic diseases with arterial stenosis.

Target Coil Embolization Using the Combined Transarterial and Transvenous Balloon-assisted Technique for Traumatic Direct Carotid Cavernous Fistula.

Herein, we describe a case of traumatic direct carotid cavernous fistula (DCCF) treated with target coil embolization using the combined transarterial and transvenous balloon-assisted technique. The patient was a 59-year-old woman who had been involved in a vehicular accident. She was admitted to the hospital due to chemosis and exophthalmos. Cerebral angiography revealed a shunt from the internal carotid artery (ICA) to the cavernous sinus (CS), which indicated DCCF. Thus, target coil embolization using the combined transarterial and transvenous balloon-assisted technique was performed. Angiography was performed 1 week after surgery to confirm the disappearance of DCCF. No recurrence was observed during the 1-year follow-up after treatment. Thus, target coil embolization using the combined transarterial and transvenous balloon-assisted technique is safe and effective for the treatment of traumatic DCCF.

Rare clinical presentations of pleomorphic xanthoastrocytoma with a high proliferative index: Two case reports.

INTRODUCTION: Pleomorphic xanthoastrocytomas (PXA) are rare, typically benign, slow-growing tumors that commonly occur in the cerebral hemispheres. We describe two cases of clinically aggressive PXA with uncommon locations; one was in the tectal plate, and the other had simultaneous multicentric lesions. PATIENT CONCERNS: The both cases presented with severe headache with no significant past medical history. DIAGNOSIS: PXA World Health Organization grade II were histopathologically diagnosed from surgically resected specimens, and immunohistochemical and sequence analysis revealed a high Ki-67 proliferative index and BRAF V600E mutation in both the cases. INTERVENTIONS: The first case presented with multicentric lesions and underwent partial resection, whereas the second case presented with a tectal plate tumor that was managed by gross total surgical resection. Strong 5-aminolevulinic acid (5-ALA)-induced fluorescence was observed in both the lesions. Postoperative radiotherapy plus concomitant and adjuvant temozolomide was administered to both the patients. OUTCOMES: Despite completing adjuvant chemo-radiotherapy, both the patients had local tumor recurrence at 2 and 5 months after the operation, respectively. CONCLUSION: The progressive clinical courses in our cases suggest that additional postoperative therapy should be considered during the treatment of PXA with a high Ki67 index, and that temozolomide with radiotherapy, followed by temozolomide maintenance therapy, may not prevent recurrence in such tumors. Importantly, our experience implies that unlike other subtypes of low grade gliomas, 5-ALA fluorescence is useful for intraoperative visualization of PXA.

A Patient with a Ruptured Blood Blister-like Aneurysm of the Internal Carotid Artery in Whom Two LVIS Stents Were Inserted.

Objective: We report a case in which multiple overlapping low-profile visualized intraluminal support (LVIS) stents were used as monotherapy for ruptured blood blister-like aneurysm (BBA) of the internal carotid artery (ICA). Case Presentation: A 48-year-old female presented to the emergency room with acute-onset headache. She was alert without neurological deficit with subarachnoid hemorrhage (SAH) Hunt and Kosnik grade I. Emergency angiography revealed a BBA from the supraclinoid ICA. This aneurysm had a small diameter, which makes coil embolization difficult. Therefore, we planned to use multiple overlapping LVIS stents as monotherapy for the ruptured aneurysm. The postoperative course was uneventful without rebleeding. The patient exhibited no neurological deficits on the clinical follow-up at 1 year. Conclusion: Multiple overlapping LVIS stents as monotherapy is useful for ruptured BBAs of the ICA.

A Patient with an Unruptured Aneurysm in the Internal Carotid Artery-duplicated Middle Cerebral Artery on Whom Coil Embolization with Balloon Remodeling Was Performed.

Objective: Treatment of an unruptured aneurysm at the origin of duplicated middle cerebral artery (DMCA) by coil embolization using balloon remodeling has not been reported. We report a case of coil embolization using balloon remodeling for an unruptured aneurysm at the origin of DMCA. Case Presentation: A 71-year-old female was found to have an unruptured aneurysm at the origin of DMCA during an examination for headache. Coil embolization using balloon remodeling for the wide neck aneurysm to preserve both the internal carotid artery (ICA) and DMCA was successful. The perioperative course was uneventful. Conclusion: This treatment enables complete embolization, and preserves both the ICA and DMCA. Thus, it is useful for aneurysms at the origin of DMCA.

Clinical relevance of BRAF status in glial and glioneuronal tumors: A systematic review.

Alterations in the BRAF gene have been reported to play a key role in the tumorigenesis of various tumors. Recent studies have shown the existence of BRAF alterations in ganglioglioma (GG), pilocytic astrocytoma (PA), pleomorphic xanthoastrocytomas (PXA), and epithelioid glioblastoma (eGBM). The focus of this review was the association between the clinical characteristics and BRAF status in these glial and glioneuronal tumors. The BRAF abnormalities, KIAA1549-BRAF fusion and BRAF mutation, were detected in approximately 50% of the analyzed tumors regardless of the tumor location, and there were site-specific BRAF abnormalities that became more remarkable on analysis by each tumor subtype. The median age of patients with KIAA1549-BRAF fusion was much lesser than that of those with BRAF mutations. Histological analysis indicates that the existence of KIAA1549-BRAF fusion is related to pilocytic morphology. The review of imaging features indicated that cyst formation is associated with the existence of KIAA1549-BRAF fusion in PA and GG and the lack of BRAF mutation in GG. Hemorrhage was significantly present in cases of GG with KIAA1549-BRAF fusion, but no relevance was shown in cases with BRAF mutations. No significant relevance was detected between the presence of calcification and BRAF alterations. Our clinical and genetic review of BRAF-related tumors indicated that the KIAA1549-BRAF fusion was strongly associated with PA, but not with other glial and glioneuronal tumors.

Carotid surgical cut-down technique for neuroendovascular therapy.

BACKGROUND: Neuroendovascular therapy is typically performed via the femoral artery, but there are rare cases in which a tortuous upstream angioarchitecture makes it difficult to access the intracranial circulation via this route. METHODS: In this case series, we describe six cases treated by surgical cut-down in the neck, with puncture of the carotid artery. Antiplatelet and anticoagulation agents were used in all cases. The indications for the technique were postsurgical thoracic aortic aneurysm (two cases), postsurgical abdominal aortic aneurysm (one case), major vessel tortuosity of the common carotid artery (two cases) and aortic arch anomaly (one case). RESULTS: The surgical cut-down technique permitted successful neuroendovascular therapy. Although one patient had a small cervical haematoma, he was treated without surgical evacuation. CONCLUSION: Overall, our findings indicate that the surgical cut-down technique is safe and useful for patients in whom the femoral approach is unsuitable.

Undifferentiated sarcoma of the sphenoid sinus.

Paranasal sinuses sarcomas are rare and no treatments have been established. We report a young-adult case of sphenoid sinus sarcoma treated by carbon-ion radiotherapy. The patient presented with progressive left-sided visual impairment. A tumor was then identified and partial resection by transnasal approach was performed. The resected mass showed typical morphology of mesenchymal tumor, and morphological and molecular analyses ruled out a predominant-differentiation phenotype. The pathological diagnosis was undifferentiated sarcoma. The residual lesion was treated with carbon-ion radiotherapy, and tumor progression was absent for one year. The patient died of the tumor regrowth 20 months after initial diagnosis. Although this case had a poorer outcome compared with cases of the more-common sarcoma types, our experience suggested that carbon-ion radiotherapy is potentially beneficial in unresectable undifferentiated sarcomas cases of sphenoid sinus.

Preoperative Embolization for Skull Base Meningiomas.

The results of preoperative embolization for skull base meningiomas were retrospectively evaluated to confirm the efficacy of this procedure. Skull base meningiomas that were treated with preoperative embolization were evaluated in 20 patients. The occluded arteries, embolic materials, treatment time, excision rate, neurologic manifestations, and complications were analyzed. The embolic material was 80% liquid, 30% coils, and 15% particles. The surgery was normally completed within 3 to 5 hours. Blood loss was normally approximately 250 mL, excluding four patients having the following conditions: malignant meningioma, a large tumor located on the medial side of the sphenoidal ridge, the petroclival tumor, and infiltrated tumor into the sigmoid sinus. The mean excision rate was 90%, achieving a Simpson grade III, but 10% were graded as Simpson grade IV. No permanent complications due to the preoperative embolization occurred. No neurologic symptoms occurred after excision. Current cerebral endovascular treatment is sophisticated, and the complication rate has markedly decreased. Although it was impossible to compare directly with or without operative embolization, preoperative embolization should be actively used as part of the treatment for this benign tumor, with better understanding of dangerous anastomosis.

A Single Center Experience with Coil Embolization for Cerebral Aneurysms Greater than 10 mm in the Internal Carotid Artery.

We investigated endovascular treatment for 10 mm or larger aneurysms in the internal carotid artery (IC), including the cavernous portion, the paraclinoid portion, and the posterior communication artery (PC). Between 2011 and 2014 at our hospital, there were 35 cases of aneurysms that were 10 mm or larger in the carotid artery. We analyzed these 35 cases retrospectively based on the size and location of the aneurysms, method of treatment, number of coils implanted, use of a stent, complications, rupture after treatment, ophthalmologic symptoms, and need for re-treatment. There was no bleeding after treatment. Of the 35 cases, four cases (11%) had permanent complications. Re-treatment was indicated in 11 cases (31%), including eight cases localized in the paraclinoid portion, two cases in the IC-PC, and one case in the cavernous portion. Among these re-treatment cases, two cases required a third treatment. Of the 16 cases with paraclinoid aneurysms, half required re-treatment. Of the 12 cases with ophthalmologic symptoms prior to treatment, 9 (75%) improved or had no change and 3 (25%) became worse. There were no complications in the 13 re-treatment procedures. Re-treatment is not uncommon, and a scheduled follow-up is needed. Coil embolization has been one of the main options for aneurysms that are 10 mm or larger in the IC. In the future, these large aneurysms will be treated with a flow diverter stent (FD).