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AbstractObjective:To report the first case of mandibular branch haemangioma of the trigeminal nerve causing erosion of the petrous carotid canal. The radiological and histological findings in this case are reviewed.Case report:A 60-year-old woman presented with severe, right-sided facial pain and paraesthesia. There were no associated symptoms of facial weakness or diplopia. A magnetic resonance imaging scan with gadolinium enhancement was performed. This showed a lesion slightly compressing the right Meckel's cave and eroding the right petrous carotid canal, occupying the foramen ovale and extending to the pterygoid muscle. The lesion was removed via a subtemporal approach.Conclusion:Haemangiomas are usually found on the skin and in other soft tissues. However, this rare tumour should also be considered in the differential diagnosis of lesions occupying Meckel's cave and the foramen ovale. [ABSTRACT FROM AUTHOR]

Background: Cerebello-pontine AVMs (CPAVMs) and petrous apex dural arteriovenous fistulae (DAVFs) are rare and sometimes difficult to distinguish. We report a fatal hemorrhagic complication after coil embolization of the petrosal vein draining a trigeminal AVM misdiagnosed as a DAVF., Case Presentation: A 73-year-old woman with a petrous apex arteriovenous shunt with dual dural and pial arterial supply presented with posterior fossa hemorrhage. The draining petrosal vein was catheterized and coiled via the superior petrosal sinus. Two episodes of contrast extravasation occurred during coiling, but the lesion was completely occluded at the end of the procedure. The patient developed a fatal posterior fossa hemorrhage in the recovery room. Microscopic pathology revealed numerous dilated vessels within the trigeminal nerve., Conclusion: CPAVMs and DAVFs with pial drainage should be distinguished pre-operatively. Occlusion of a pial vein (as opposed to a sinus) in the treatment of an arteriovenous shunt carries hemorrhagic risk if a liquid embolic agent is not used to completely occlude all pathological vessels.

We present the case of a 31-year-old woman who underwent surgical excision for a polypoid, vulvar lesion. Histopathological analysis showed a diffuse myxoid stroma admixed with scant collagen fibrils. Thin-walled and branching blood vessels were prominent, with a mild perivascular lymphocytic infiltrate. Cytologically bland spindle cells with inconspicuous nucleoli were immersed in a loose myxoid stroma. This combination of histopathological features along with multinodularity in the subcutaneous fat raised concern for deep angiomyxoma, a locally destructive neoplasm. Among our differential of myxoid lesions of the vulva, we ultimately favored the diagnosis of vulvar cutaneous myxoma. Upon further investigation, we learned that our patient was indeed known for the Carney complex. We highlight that vulvar cutaneous myxomas arising in the context of the Carney complex pose a significant diagnostic challenge for pathologists and should not be overdiagnosed as aggressive lesions such as deep angiomyxoma or other malignant stromal neoplasms.

Medulloblastoma is an aggressive primary brain tumor that is extremely rare in adults; therefore, prospective studies are limited. We reviewed the information of all MB patients treated at the CHUM between 2006 and 2017. We divided our cohort by age and further divided adult patients (53%) in two groups, those diagnosed between 2006-2012 and 2013-2017. In our adult population, median follow up was 26 months and SHH-activated MB comprised 39% of tumors. Adult 5yOS was 80% and first-line therapy led to a 5yPFS of 77%. The absence of radiosensitizing chemotherapy (100% vs. 50%; p = 0.033) negatively influenced 5yPFS. 96% of adult patients received radiotherapy and 48% of them received concomitant radiosensitizing chemotherapy. Complete surgical resection was performed on 85% of adults, but the extent of resection did not have a discernable impact on survival and did not change with time. Adjuvant chemotherapy did not clearly affect prognosis (5yOS 80% vs. 67%, p = 0.155; 5yPFS 78% vs. 67%, p = 0.114). From 2006-2012, the most common chemotherapy regimen (69%) was Cisplatinum, Lomustine and Vincristine, which was replaced in 2013 by Cisplatinum, Etoposide and Cyclophosphamide (77%) with a trend for worse survival. Nine patients recurred and seven of these (78%) were treated with palliative chemotherapy. In conclusion, we did not identify prognostic demographic or tumor factors in our adult MB population. The presence of radiosensitizing chemotherapy was associated with a more favorable PFS. Cisplatinum, Lomustine and Vincristine regimen might be a better adjuvant chemotherapy regimen.

Background: Rupture of spinal aneurysms is a rare cause of subarachnoid hemorrhage. These aneurysms are often associated with a variety of vascular malformations that increase blood flow in the spinal circulation or with disorders that compromise the vessel wall. However, spinal aneurysms may be isolated, not associated with any known predisposing condition. The objective of this study is to explore the possible mechanisms associated with the formation and rupture of isolated spinal aneurysms (ISAs)., Methods: We conducted a retrospective review of a series of consecutive patients admitted for a ruptured ISA. In all cases, spinal angiography confirmed the presence of a spinal aneurysm responsible for the bleeding. Particular attention was paid to medical history and symptoms before bleeding, for potential factors predisposing to their formation and rupture., Results: Between 2008 and 2020, ten cases of spinal aneurysms were seen at our institution including 4 cases of ISA. All patients with ISA were female, and in 3 cases the aneurysm involved the territory of the posterior spinal artery. In 3 of these 4 (75%) ISA cases, there was a strikingly similar history of retching and vomiting preceding the thunderclap headache. In 1 patient, the aneurysm was surgically resected; pathologic analysis revealed a fusiform dissecting aneurysm. All 4 patients had a favorable outcome., Conclusions: We suggest that the straining during prolonged retching and vomiting plays a role in the formation and rupture of some ISAs, possibly because of pressure spikes, increased transmural arterial pressure, and increased wall shear stress during straining., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Corticotroph tumor progression (CTP) or Nelson's syndrome (NS) can occur in patients with Cushing's disease (CD) following bilateral adrenalectomy. It has rarely been observed in patients treated with long-term medical therapy for persistent CD. Osilodrostat (LCI699) is a new steroidogenesis inhibitor of 11β-hydroxylase (CYP11β1) that induced remission of hypercortisolism in 86% of patients with refractory CD in the randomized placebo-controlled trial LINC-3 (NCT02180217)., Methods: A 40-year-old woman with persistent CD following transsphenoidal surgery was treated with osilodrostat in the LINC-3 trial and was followed with regular hormonal assessments and imaging of residual corticotroph tumor., Results: Under oral therapy with osilodrostat 10 mg twice daily, urinary free cortisol (UFC) normalized and clinical signs of CD regressed during therapy. However after 4 years of treatment, ACTH levels increased from 73 to 500 pmol/L and corticotroph tumor size increased rapidly from 3 to 14 mm, while UFCs remained well controlled. Surgical resection of an atypical tumor with weak ACTH expression and increased proliferative index (Ki-67 ≥ 8%) resulted in current remission but will require close follow-up., Conclusion: This case highlights the importance of monitoring ACTH and corticotroph tumor size in patients with persistent CD, either under effective treatment with steroidogenesis inhibitors or after bilateral adrenalectomy.

Background: Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare tumor-like lesion with unknown pathogenesis. It is likely under-reported due to diagnostic challenges including the nonspecific radiographic features, lack of diagnostic markers, and often asymptomatic nature of the lesions., Methods: We performed detailed examination of 11 CAPNON specimens diagnosed by histopathology, with the help of electron microscopy and immunohistochemistry., Results: Electron microscopy revealed the presence of fibrillary materials consistent with neurofilaments. In addition to some entrapped axons at the periphery of CAPNONs, we discovered that all specimens stained positive for neurofilament-light (NF-L) within the granular amorphous cores, but not neurofilament-phosphorylated (NF-p). CAPNONs also showed variable infiltration of CD8+ T-cells and a decreased ratio of CD4/CD8+ T-cells, suggesting an immune-mediated process in the pathogenesis of CAPNON., Conclusion: NF-L and CD4/CD8 immunostains may serve as diagnostic markers for CAPNON and shed light on its pathogenesis.

Natalizumab is used as a second-line treatment for multiple sclerosis (MS). Some reports have linked natalizumab to primary central nervous system lymphoma (PCNSL), although few have described its management. A 45-year-old woman with Balo's Concentric Sclerosis presented dizziness, vertigo accompanied by dysarthria, weakness on the left side and blurred vision to the right eye after the fourth dose of natalizumab. Magnetic resonance imaging (MRI) and a brain biopsy confirmed the diagnosis of PCNSL. The patient received modified PCNSL chemotherapy (MATRix protocol) followed by high-dose chemotherapy (HDC) supported by an autologous hematopoietic stem cell transplant (ASCT) as a consolidation therapy. Thirty months later, she is still in complete remission of her PCNSL and MS. In this case, whole brain radiotherapy was excluded because it may be associated with an increased risk of neurotoxicity in MS. ASCT was preferred because it has been shown to prevent disability progression in less advanced MS stages. Our patient is the second to receive an ASCT in this context and this option of treatment should be the preferred if the patient is eligible.

Inflammatory myofibroblastic tumors (IMT) of the central nervous system (CNS) are rare entities that have a predilection for local recurrences. Approximately half of the inflammatory myofibroblastic tumors contain translocations that result in the over-expression of the anaplastic lymphoma kinase (ALK) gene. We hereby present the case of a patient diagnosed with a left parieto-occipital IMT that recurred after multiple surgeries and radiotherapy. Immuno-histochemical examination of the tumor demonstrated ALK overexpression and the presence of an ALK rearrangement observed in lung cancers. The patient was subsequently started on an ALK inhibitor. A response evaluation criteria in solid tumors (RECIST) partial response was observed by the seventh month of ALK inhibition and the tumor remained in control for 14 months. The current case reiterates the activity of ALK inhibitors within the CNS and suggests that radiotherapy may potentiate the permeability of ALK inhibitors in CNS tumors addicted to ALK signalling., Competing Interests: The authors have declared financial relationships, which are detailed in the next section.

Innovations in endovascular tools have permitted an increasingly broad range of neurovascular lesions to be treated via minimally invasive methods. However, some device modifications may carry additional risks, not immediately apparent to operators. A patient with a symptomatic, partially thrombosed basilar apex aneurysm was allocated balloon-assisted coiling. Attempts were made to place a microwire across the basilar apex through the posterior communicating artery. Overlapping courses of the posterior cerebral and posterior choroidal arteries on the roadmap images were not recognized and a flanged-tip microwire was inadvertently advanced deep into the choroidal artery. Following the wire with a microcatheter led to binding of arterial tissue within the microcatheter. Removing the wire led to an avulsion of the choroidal artery and a severe hemorrhagic complication which proved fatal. Tissue was identified on the tip of the guidewire. Pathology showed layers of vascular tissue within the laser-cut flanges of the distal wire tip. A similar complication, also fatal, occurred during balloon angioplasty of a distal vertebral artery, when an exchange wire was accidently introduced into a perforator from a posterior cerebral artery. Ex vivo catheterization of distal mesenteric arterial branches showed that the wall of small arteries can be entrapped by laser-cut, flanged, but not by smooth guidewire tips. Microwires with a flanged instead of smooth distal tip, when placed into small caliber vessels, may cause hemorrhagic complications from avulsions*.

Haemorrhagic complications can occur following aneurysm treatment with flow diverters (FD), but the underlying mechanism remains unknown. We describe a case where deformation of the device may have contributed to the complication. A patient with a giant, previously unruptured cavernous aneurysm that extended intracranially to cause oedema of the internal capsule was treated with flow diversion. Treatment was followed by multiple episodes of peri-aneurysmal haemorrhages within eight days. A deformation of the device which occurred where it curved to cross the aneurysm neck created residual flows which, in the presence of a stent stenosis immediately beyond the neck, may have contributed to the observed ruptures. Following multiple haemorrhages the patient subsequently died. Autopsy demonstrated early red thrombus partially bridging the struts of the flow diverter, and intra-aneurysmal thrombus of various ages. Microscopic pathology showed an aneurysm wall consisting of collagen infiltrated with neutrophils, but the wall was absent near the cerebral peduncle, adjacent to the brain haemorrhage. Radiographs of the extracted specimen confirmed deformation of the FD construct, located at the transition zone of the stent, leading to increased pore size and porosity. The site of the deformation correlated with the angiographic presence of a continued blood inflow jet into the aneurysm. Stent deformation at the transition zone may promote persistent blood entry into the aneurysm, and in turn potentially contribute to haemorrhagic complications.

Background: Inflammatory myofibroblastic tumors (IMTs) of the central nervous system (CNS) are rare entities with diverse histopathological features and varying propensities to recur., Case Description: A 26 year-old male with an IMT of the CNS of the left tentorium had tumor progression 2 months after partial surgical resection. Histopathological studies confirmed expression of ALK. Macroscopic total resection was performed followed by radiotherapy. A recurrence occurred 20 months after the second surgery that necessitate reoperation. Including the present case, we identified 30 cases of IMT of the CNS corresponding to our search criteria in the literature. The extent of resection was reported in 26 of these cases. Gross total resection was done in 75% of ALK-positive and in 61% of ALK-negative cases. Recurrence rate after gross total resection for ALK-positive and ALK-negative cases was 33% and 9%, respectively. Every recurrence in ALK-positive patients occurred within 2 years after surgery., Conclusion: IMT of the CNS are a heterogeneous group of tumors and the treatment of choice is complete surgical resection. Because of the high recurrence rate reported for IMT of the CNS expressing ALK, a closed follow-up is recommended. When faced with an early recurrence, a surgical resection followed by radiotherapy may be advised.

Background and Purpose: The relationship between aneurysm dimensions, flow, thrombosis, and rupture remains poorly understood. We attempted to clarify this relationship by exploring various swine aneurysm models., Materials and Methods: Bilateral carotid aneurysms were constructed according to 3 protocols in 24 animals: small aneurysms with wide necks (group 1; n = 6 animals); small aneurysms with small necks (group 2; n = 4 animals), and giant aneurysms with large necks (group 3; n = 14 animals). Group 3 included 3 subgroups, related to testing the model in various experimental conditions: The neck was clipped in 3 animals; venous pouches lacked an endothelial lining in 4 animals; and 7 were control animals. Animals were followed until rupture, or for 1-4 weeks. Angiography was performed postoperatively and before euthanasia. We studied lesion pathology, paying attention to thrombosis, recanalization, wall composition, and perianeurysmal hemorrhage., Results: Groups differed significantly in aneurysm dimensions and aspect ratio (P = .002). Ruptures occurred more frequently in animals with untreated giant aneurysms (7/7) than in animals with small wide-neck (0/6) or small-neck (2/4) aneurysms (P = .002). Ruptures occurred only in animals with thrombosed aneurysms. Lesions lacking an endothelial lining and 5 of 6 clipped venous pouches thrombosed but did not rupture. One giant lesion ruptured despite complete clipping. The wall was deficient in α-actin and was infiltrated with inflammatory cells and erythrocytes in all thrombosed cases, ruptured or not. Ruptures were associated with recanalizing channels in 9 of 10 cases., Conclusions: Thrombosis, inflammation, and recanalization may precipitate aneurysmal ruptures in a swine model.

It has been suggested that treatment with adequate dose titration of pegvisomant, a GH antagonist, up to a maximum of 40 mg daily, can achieve IGF-1 normalisation in virtually all patients with acromegaly. On the other hand, temozolomide (TMZ), an alkylating cytostatic agent, has been reported to reduce pituitary tumour size and hormone hypersecretion in a small number of aggressive pituitary macroadenomas. In this paper we report the case of a patient resistant to very high doses of pegvisomant used in combination with somatostatin analogs (SSA) and to TMZ therapy. The patient, initially a 22 year-old man with an invasive GH-secreting pituitary macroadenoma (IGF-1, 371% upper limit of normal), had active acromegaly despite a repeat transsphenoidal surgery followed by radiotherapy and SSA (octreotide 800 μg sc daily) (IGF-1, 262% ULN). In combination with SSA, pegvisomant was started at 20 mg daily and doses were titrated up to 60 mg daily. IGF-1 was moderately reduced and stabilized at 200% ULN after 1 year of treatment. Serum pegvisomant level was 30,500 ng/l, the denaturalized GHBP concentration 1,120 pM and the endogenous GH level was 220 μg/l. Pegvisomant was stopped and TMZ therapy was given for 5 cycles. However, the patient reported an increase of acromegaly symptoms and the serum IGF-1 was raised to the same level prior to pegvisomant therapy. Consequently, pegvisomant was tried again with doses up to 100 mg daily finally resulting in normalisation of serum IGF-1 level and improvement of acromegaly symptoms and patient well-being. We conclude that in some patients with severe acromegaly refractory to multimodal therapy, biochemical control may be difficult to attain with conventional doses of pegvisomant or TMZ therapy.

Cushing's disease is caused by glucocorticoid-resistant pituitary corticotroph adenomas. We have previously identified the loss of nuclear Brg1 as one mechanism that may lead to partial glucocorticoid resistance: this loss is observed in about 33% of human corticotroph adenomas. We now show that Brg1 loss of function correlates with cyclin E expression in corticotroph adenomas and with loss of the cell cycle inhibitor p27(Kip1) expression. Because Brg1 is thought to have tumor suppressor activity, the present study was undertaken to understand the putative contribution of cyclin E derepression produced by loss of Brg1 expression on adenoma development. Overexpression of cyclin E in pituitary proopiomelanocortin cells leads to abnormal reentry into cell cycle of differentiated proopiomelanocortin cells and to centrosome instability. These alterations are consistent with the intermediate lobe hyperplasia and anterior lobe adenomas that were observed in these pituitaries. When combined with the p27(Kip1) knockout, overexpression of cyclin E increased the incidence of pituitary tumors, their size, and their proliferation index. These results suggest that cyclin E up-regulation and p27(Kip1) loss-of-function act cooperatively on pituitary adenoma development.

The simultaneous occurrence of a hypothalamic and sellar gangliocytoma with a pituitary prolactinoma is very rare. The explanation for such an association is not known. We describe the case of a woman who had a coexisting adjacent pituitary prolactinoma and gangliocytoma within the same sellar mass. The tumor cells of the gangliocytoma demonstrated expression of enkephalin, a product of proopiomelanocortin known to be a prolactin secretagogue. We postulate that in this patient there may be a link between gangliocytoma enkephalin and prolactin hypersecretion.

The blood-brain barrier (BBB) restricts molecular and cellular trafficking between the blood and the CNS. Although astrocytes are known to control BBB permeability, the molecular determinants of this effect remain unknown. We show that angiotensinogen (AGT) produced and secreted by astrocytes is cleaved into angiotensin II (AngII) and acts on type 1 angiotensin receptors (AT1) expressed by BBB endothelial cells (ECs). Activation of AT1 restricts the passage of molecular tracers across human BBB-derived ECs through threonine-phosphorylation of the tight junction protein occludin and its mobilization to lipid raft membrane microdomains. We also show that AGT knock-out animals have disorganized occludin strands at the level of the BBB and a diffuse accumulation of the endogenous serum protein plasminogen in the CNS, compared with wild-type animals. Finally, we demonstrate a reduction in the number of AGT-immunopositive perivascular astrocytes in multiple sclerosis (MS) lesions, which correlates with a reduced expression of occludin similarly seen in the CNS of AGT knock-out animals. Such a reduction in astrocyte-expressed AGT and AngII is dependent, in vitro, on the proinflammatory cytokines tumor necrosis factor-alpha and interferon-gamma. Our study defines a novel physiological role for AngII in the CNS and suggests that inflammation-induced downregulation of AngII production by astrocytes is involved in BBB dysfunction in MS lesions.

Negative feedback regulation of the proopiomelanocortin (POMC) gene by the glucocorticoid (Gc) receptor (GR) is a critical feature of the hypothalamo-pituitary-adrenal axis, and it is in part exerted by trans-repression between GR and the orphan nuclear receptors related to NGFI-B. We now show that Brg1, the ATPase subunit of the Swi/Snf complex, is essential for this trans-repression and that Brg1 is required in vivo to stabilize interactions between GR and NGFI-B as well as between GR and HDAC2. Whereas Brg1 is constitutively present at the POMC promoter, recruitment of GR and HDAC2 is ligand-dependent and results in histone H4 deacetylation of the POMC locus. In addition, GR-dependent repression inhibits promoter clearance by RNA polymerase II. Thus, corecruitment of repressor and activator at the promoter and chromatin modification jointly contribute to trans-repression initiated by direct interactions between GR and NGFI-B. Loss of Brg1 or HDAC2 should therefore produce Gc resistance, and we show that approximately 50% of Gc-resistant human and dog corticotroph adenomas, which are the hallmark of Cushing disease, are deficient in nuclear expression of either protein. In addition to providing a molecular basis for Gc resistance, these deficiencies may also contribute to the tumorigenic process.

Primary brain tumors, particularly glioblastomas (GB), remain a challenge for oncology. An element of the malignant brain tumors' aggressive behavior is the fact that GB are among the most densely vascularized tumors. To determine some of the molecular regulations occuring at the brain tumor endothelium level during tumoral progression would be an asset in understanding brain tumor biology. Caveolin-1 is an essential structural constituent of caveolae that has been implicated in mitogenic signaling, oncogenesis, and angiogenesis. In this work we investigated regulation of caveolin-1 expression in brain endothelial cells (ECs) under angiogenic conditions. In vitro, brain EC caveolin-1 is down-regulated by angiogenic factors treament and by hypoxia. Coculture of brain ECs with tumoral cells induced a similar down-regulation. In addition, activation of the p42/44 MAP kinase is demonstrated. By using an in vivo brain tumor model, we purified ECs from gliomas as well as from normal brain to investigate possible regulation of caveolin-1 expression in tumoral brain vasculature. We show that caveolin-1 expression is strikingly down-regulated in glioma ECs, whereas an increase of phosphorylated caveolin-1 is observed. Whole-brain radiation treatment, a classical way in which GB is currently being treated, resulted in increased caveolin-1 expression in tumor isolated ECs. The level of tumor cells spreading around newly formed blood vessels was also elevated. The regulation of caveolin-1 expression in tumoral ECs may reflect the tumoral vasculature state and correlates with angiogenesis kinetics., (Copyright 2003 Wiley-Liss, Inc.)

Background: Infantile and juvenile forms of Alexander disease are well characterized and are caused by de novo mutations in the glial fibrillary acid protein (GFAP) gene. In contrast, the adult form of the disease has been rarely described, and the etiology of this variant remains unknown., Objective: To characterize the clinical phenotype and identify the gene causing an autosomal dominant form of adult Alexander disease., Methods: We identified a large kindred segregating clinical features compatible with adult Alexander disease in an autosomal dominant fashion. A neurological examination was performed on all affected members of this family. Most of these patients also underwent magnetic resonance imaging of the brain and a polysomnographic study. The diagnosis was confirmed pathologically in 2 individuals. We screened all coding regions of the GFAP gene in affected individuals by means of direct sequencing and single-stranded conformational polymorphisms analysis., Results: We found a novel D78E mutation in GFAP in all affected individuals. This mutation was not detected in more than 100 control subjects. Clinical and radiological features of affected individuals were clearly different from those of patients with the infantile and juvenile forms of the disease. The most consistent finding was the presence of bulbar signs. In addition, sleep disturbance (mainly sleep apnea), symptoms of dysautonomia, and dysmorphism were found in all affected individuals. In younger patients, magnetic resonance imaging showed T2 signal abnormalities in the medulla compatible with an area of demyelination. In contrast, in older patients, we found marked atrophy of the medulla without signal abnormalities. None of the affected individuals exhibit signs of demyelination of the cerebral white matter., Conclusions: The present study is the first demonstration of a mutation in GFAP that causes an autosomal dominant form of Alexander disease and establishes the existence of the adult variant. Clinical evaluation in individuals carrying mutation in the GFAP gene allowed a better definition of this heterogeneous clinical syndrome and will help increase its recognition in neurological practice.

Endothelial cells (ECs) are new targets for tumor therapy. In this work, we purified endothelial cells from intracerebral and subcutaneous experimental gliomas as well as from normal brain in order to define some of the phenotypical differences between angiogenic and quiescent brain vasculature. We show that the multidrug resistance genes encoding drug efflux pumps at the brain endothelium are expressed differently in normal and tumoral vasculature. We also show that ECs from gliomas present increased activity of gelatinase B (MMP9), key enzyme in the angiogenic process. Importantly, we observe a different phenotype between ECs in the intracerebral and subcutaneous models. Our results provide molecular evidence of phenotypic distinction between tumoral and normal brain vasculature and indicate that the EC phenotype depends on interactions both with tumor cells and also with the microenvironment.

1. The blood-brain barrier (BBB) contributes to brain homeostastis and fulfills a protective function by controlling the access of solutes and toxic substances to the central nervous system (CNS). The efflux transporter P-glycoprotein (P-gp) is a key element of the molecular machinery that confers special permeability properties to the BBB. 2. P-gp, which was initially recognized for its ability to expel anticancer drugs from multidrug-resistant cancer cells, is strongly expressed in brain capillaries. Its expression in the BBB limits the accumulation of many hydrophobic molecules and potentially toxic substances in the brain. 3. The purpose of this review is to summarize the current state of knowledge about the expression of P-gp, its cellular localization as well as its possible functions in the BBB.

Background and Purpose: Cyanoacrylates are effective occlusive agents in neurovascular interventions. To study their potential to improve long-term results of endovascular treatment of aneurysms, we conducted experimental studies in canine aneurysm models., Methods: Venous pouch carotid aneurysms were constructed in dogs. Results of coil embolization of lateral wall and bifurcation aneurysms were compared. A lateral wall model of embolization with gelatin sponges was used to study the effects of coating sponges with cyanoacrylate on angiographic results and neointima thickness at 3 and 12 weeks. These models were also used to investigate the control of endovascular cyanoacrylate deposition, alone or over a coil placed at the neck of the treated lesions. The results of endovascular cyanoacrylate embolization of bifurcation aneurysms were compared with those of coil embolization at 3 months., Results: Bifurcation aneurysms treated with coils showed more frequent recurrences (P <.01) and thinner neointimas (P <.01) at 3 months than did lateral wall aneurysms. Cyanoacrylate-coated sponges improved angiographic results (P <.05) and led to thicker neointimas at 3 and 12 weeks (P <.05) as compared with uncoated sponges. Endovascular cyanoacrylate deposition with microcatheters led to stray emboli in all cases. Cyanoacrylate delivery was improved by a single coil positioned at the neck of the aneurysm, but parent vessel embolization still occurred in 25% of the animals. Cyanoacrylate embolization of bifurcation aneurysms improved angiographic results at 3 months as compared with coil embolization (P <.01)., Conclusion: Cyanoacrylate embolization is currently difficult to control. It has the potential to decrease recurrences after endovacular treatment of aneurysms, but a safe method for endovascular delivery has yet to be developed.

Astrocytic tumors are the most common human brain tumors. Establishment of tumor grade is a key determinant both in the choice of a therapeutic approach and in the prognosis. The diagnosis of astrocytic tumors is currently determined following histopathological analysis. The identification of molecular markers would offer a complementary tool for characterizing tumors with respect to their clinical behavior. In this study we determined the expression levels of 3 small GTP binding proteins (RhoA, RhoB and Rac1), of their inhibitor RhoGDI and of caveolin-1 in 24 human astrocytic tumors of grades I to IV. Our results demonstrated that the expression of RhoA and RhoB decreased significantly in all brain tumors studied and was inversely related with tumor of grade II to IV malignancy. The amount of caveolin-1 immunodetected was not significantly different from normal brain samples while the Rac1 expression level was diminished in astrocytic tumors of grades III and IV. Our finding that RhoA and RhoB expression levels are correlated to tumor malignancy suggests that they may serve as novel and efficient diagnostic markers for astrocytic brain tumors of histological grade II to IV and complement currently applied histopathological analysis.