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.

[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.

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.

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.

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.

Intracranial endodermal cyst presenting with nonobstructive hydrocephalus: A case report.

RATIONALE: Endodermal cysts are rare benign lesions in the central nervous system. Their common symptoms include headache and neck pain caused by mass effect or inflammatory reaction. We report the case of an elderly woman with intracranial endodermal cyst who presented with nonobstructive hydrocephalus. PATIENT CONCERNS: A 78-year-old woman presented with acute deterioration of consciousness caused by acute hydrocephalus. She subsequently underwent ventriculoperitoneal shunt placement. Eighteen months after this operation, she developed numbness of extremities and gait and progressive cognitive disturbances. DIAGNOSIS: Initially, the endodermal cyst could not be recognized, but it became clinically evident in the craniocervical junction after ventriculoperitoneal shunt placement. MRI revealed multiple cystic lesions in the pontomedullary cistern. Postoperative pathology confirmed the diagnosis of endodermal cyst. INTERVENTIONS: Subtotal resection of the cystic lesion was performed. Intra-operatively, multiple cysts containing a milky white fluid were noted and the medullary surface including the median and lateral apertures of the fourth ventricle were covered by thick, cloudy arachnoid membrane. OUTCOMES: Although the numbness of extremities improved after the surgery, she remained bedridden due to deterioration in cognitive function and generalized muscle weakness. The patient developed recurrence 2 months after the surgery; however, no additional surgery was performed owing to her poor general condition. LESSONS: Endodermal cysts rarely present with nonobstructive hydrocephalus caused by recurrent meningitis. In such cases, the lesions are often invisible on initial diagnostic imaging, and complete resection of the lesions is typically difficult because of strong adhesion between the cyst walls and contiguous vital structures.

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.

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).

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.

Novel system evaluating in vivo pathogenicity of desmoglein 3-reactive T cell clones using murine pemphigus vulgaris.

Autoreactive T cells are thought to be involved in the pathogenesis of autoimmune diseases, but evidence for their direct pathogenicity is almost lacking. Herein we established a unique system for evaluating the in vivo pathogenicity of desmoglein 3 (Dsg3)-reactive T cells at a clonal level in a mouse model for pemphigus vulgaris (PV), an autoimmune blistering disease induced by anti-Dsg3 autoantibodies. Dsg3-reactive CD4(+) T cell lines generated in vitro were adoptively transferred into Rag-2(-/-) mice with primed B cells derived from Dsg3-immunized Dsg3(-/-) mice. Seven of 20 T cell lines induced IgG anti-Dsg3 Ab production and acantholytic blister, a typical disease phenotype, in recipient mice. Comparison of the characteristics between pathogenic and nonpathogenic Dsg3-reactive T cell lines led to the identification of IL-4 and IL-10 as potential factors associated with pathogenicity. Further in vitro analysis showed that IL-4, but not IL-10, promoted IgG anti-Dsg3 Ab production by primed B cells. Additionally, adenoviral expression of soluble IL-4Ralpha in vivo suppressed IgG anti-Dsg3 Ab production and the PV phenotype, indicating a pathogenic role of IL-4. This strategy is useful for evaluating the effector function of autoreactive T cells involved in the pathogenesis of various autoimmune diseases.

Conformational epitope mapping of antibodies against desmoglein 3 in experimental murine pemphigus vulgaris.

BACKGROUND: Pemphigus vulgaris (PV) is a blistering skin disease caused by IgG autoantibodies against desmoglein 3 (Dsg3). We have recently developed an active disease mouse model for PV by adoptive transfer of splenocytes from immunized or naive Dsg3-/- mice into Rag2-/- recipient mice. OBJECTIVE: In this study, we characterized the conformational epitopes of anti-Dsg3 IgG antibodies and their pathogenic activities in the PV model mice. METHODS: The binding regions of anti-Dsg3 IgG antibodies were assessed by competition ELISAs with domain-swapped mouse Dsg1/Dsg3 molecules in PV model mice receiving immunized (n = 53) or naive (n = 56) splenocytes. To compare the pathogenic activity of antibodies against N-terminal versus C-terminal extracellular domains, Dsg3-/- mice were immunized with the residues 1-162 or the residues 403-565 of mouse Dsg3, and the splenocytes were adoptively transferred into Rag2-/- mice. RESULTS: The middle to C-terminal extracellular domains of Dsg3 (residues 195-565) showed >50% competition in 51/53 (96.2%) and 45/56 (80.4%) while the N-terminal domain (residues 1-162) showed >50% competition only in 3/53 (5.7%) and 8/56 (14.3%) in mice receiving immunized and naive splenocytes, respectively. The mice receiving Dsg3-/- splenocytes immunized with the residues 403-565 developed the PV phenotype as early as and as severely as the mice receiving splenocytes immunized with the residues 1-162. CONCLUSIONS: In PV model mice the antibodies were dominantly raised against the middle to C-terminal extracellular domains of mouse Dsg3 where amino acid sequences are less conserved among desmoglein isoforms and that those antibodies may also be involved in the blister formation.

An experimental system for a heterotopic pain stimulation study in humans.

So far heterotopic pain stimulation study has been performed in humans. Many studies have examined changes in subjective pain threshold and nociceptive somatic reflex. However, there are few studies using somatosensory evoked potentials (SEPs) for heterotopic pain stimulation study. Here we describe a new experimental system for a heterotopic pain stimulation study in humans. This system consists of three subsystems including the electrical test stimulation for teeth, the recording of SEP induced by electrical tooth stimulation and conditioning nerve stimulation. The preliminary experiment performed in eight healthy subjects indicated that the electrical test stimulation subsystem with the SEP recording subsystem is also very well indicated for subjective and objective pain evaluation, including VAS estimation and the amplitude of the SEP late component induced by electrical tooth stimulation. Under the experimental system in the present study, electrical median nerve stimulation as conditioning stimulation significantly decreased both the SEP amplitude induced by electrical tooth simulation and subjective pain expressed by the VAS. These results revealed that our experimental system works well and it is very suitable and useful for the study of the pain mechanism under heterotopic stimulation in humans.