The perianeurysmal environment: influence on saccular aneurysm shape and rupture.

PURPOSE: The purpose of this study was to evaluate whether interactions between intracranial cerebral saccular aneurysms and the perianeurysmal environment (PAE), in the form of contact constraints, influence aneurysm shape and risk of rupture. METHODS: A total of 190 consecutive aneurysms during a 34-month period were retrospectively analyzed. Of these, 124 were ruptured (group 1) and 66 were unruptured (group 2). Pretreatment high-resolution CT angiography was available for each aneurysm and was the determinant inclusion criterion. Aneurysm size and location, type of hemorrhage, initial Glasgow Coma Scale rating, World Federation of Neurological Societies grade, Fisher grade, and presence of concomitant aneurysms were recorded. Contact constraints between aneurysms and anatomical structures of the PAE were identified for each aneurysm and further subdivided into balanced or unbalanced depending on whether contact constraints occurred symmetrically on the aneurysm wall. Regular or irregular shape was recorded and correlated to contact constraints. RESULTS: Compared with unruptured aneurysms, ruptured aneurysms were found to be larger and more irregular, to develop more contact constraints with the PAE, and to show higher rates of unbalanced contact constraints. Ruptured aneurysms had a tendency to be found in locations of a constraining PAE. Irregular shape was positively correlated with the presence of an unbalanced contact constraint, even in the absence of obvious contour deformations from an imprint of an adjacent structure. CONCLUSION: The existence of contact constraints between intracranial saccular aneurysms and the PAE were shown to influence shape and risk of aneurysm rupture. Modifications of wall shear stress by contact constraints are discussed. Analysis of contact constraints between aneurysm and the PAE could be considered additional parameters in the assessment of risk of aneurysm rupture.

Expression and localization of VEGF-C and VEGFR-3 in glioblastomas and haemangioblastomas.

Primary human brain tumours account for approximately 2% of all cancers. High levels of expression of vascular endothelial growth factor-A (VEGF-A), a potent angiogenic factor, are linked to poor prognosis. In contrast, the potential role in human brain tumour biology of newer VEGF family members, VEGF-C and VEGF-D, both of which are lymphangiogenic factors, is poorly understood. In the present study, the expression of all VEGFs (VEGF-A, -B, -C, and -D) and their receptors (VEGFR-1, -2, and -3) has been assessed in 39 primary human brain tumours. The well-established findings were confirmed with VEGF-A. Surprisingly, however, VEGF-C and VEGF-D, as well as VEGFR-3, were expressed in some tumour types such as haemangioblastomas and glioblastomas, despite their lack of lymphatic vessels. VEGF-C and VEGFR-3 transcripts were localized to the tumour palisade around necrotic areas in glioblastomas and were evenly distributed throughout haemangioblastomas. VEGF-C protein was localized by immunohistochemistry to the palisade layer in glioblastomas. More than 50% of VEGF-C-positive cells also expressed the intermediate-stage inflammatory macrophage marker CD163; however, a significant proportion of VEGF-C-positive cells were CD163-negative. These data demonstrate the presence of molecules, primarily described as regulators of lymphangiogenesis, in normal human brain and brain tumours that are devoid of lymphatics. Their localization in macrophages points to a role in tumour-associated inflammation.

Early surgery for brainstem cavernomas.

BACKGROUND: The purpose was to review our experience with the surgical management of brainstem cavernomas (BSCs) and especially the impact of the surgical timing on the clinical outcome. METHOD: We retrospectively reviewed 22 patients harboring a BSC, who underwent 23 procedures. FINDINGS: Surgery was carried out during the early stage after the last haemorrhage, with a mean delay of 21.6 days (range 4-90 days). Sixteen procedures were performed after a first bleeding event while seven after multiple bleedings. Complete resection was achieved in 19 patients (86.4%). Early after surgery, 12 patients (52.2%) improved neurologically, 5 (21.7%) were stable and 6 (26.1%) worsened. New postoperative deficits were noted after 9 procedures (39.1%). Statistically significant factors for postoperative aggravation were: late surgery (P = 0.046) and multiple bleedings (P = 0.043). No patient operated on within the first 19 days after bleeding did worsen (n = 11), as opposed to 6 out of 12 who did when operated on later. After a mean follow-up of 44.9 months, 20 patients (90.9%) were improved, 1 patient (4.6%) was worse and 1 patient was lost to follow-up (4.6%), after reoperation for rebleeding of a previously completely resected cavernoma. Late morbidity was reduced to 8.6%. The mean Glasgow Outcome Scale (GOS) at the end of the follow-up period was 4.24, compared to a mean preoperative GOS of 3.22 (P<0.001). Complete neurological recovery of motor deficits, sensory disturbances, cranial nerves (CNs), internuclear ophtalmoplegia and cerebellar dysfunction were respectively 41.7%, 38.5%, 52.6%, 60.0% and 58.3%. Among the most affected CNs: CN 3, CN 5 and CN 7 were more prone to completely recover, respectively in 60.0%, 70.0% and 69.2%. CONCLUSIONS: Surgical removal of BSCs is feasible in experienced hands with acceptable morbidity and good outcome. Early surgery and single bleeding were associated with better surgical results.

Malignant transformation of a spinal cord ganglioglioma--case report and review of the literature.

Gangliogliomas are tumors of mixed glial and neuronal phenotype that usually have a benign clinical course. Rare cases display anaplastic features at the time of first presentation or progress to anaplastic gliomas over extended times. We report on a ganglioglioma of the spinal cord that recurred as a malignant glioma one and a half years after resection. The initial neoplasm was composed of a mixture of well-differentiated ganglionic and astrocytic cells. The recurrent tumor was an anaplastic small-cell glioma. The sole unusual aspect in the initial neoplasm was an abundance of small vessels with calcified walls, which mimicked a vascular malformation.

Nasopharynx paraganglioma with extension in the clivus.

Paraganglioma is a rare benign tumor arising from the sympathetic nervous system. Here we describe an exceptional case of a paraganglioma located in the nasopharynx with an extension through the clivus up to the dura. Atypically, no contact with any major vessels was found. A radical resection of the mass was performed by an anterior transmaxillary approach through a Le Fort I osteotomy. One year follow up reveals no signs of local or distant recurrence. No cosmetic changes can be observed after the surgery and nasal and masticatory functions are unmodified. We review the clinical presentation, workup of paraganglioma, as well as the surgical approaches to the clivus.

Double-lumen balloon microcatheter-assisted occlusion of cerebral vessels with coils: a technical note.

The purpose of this study was to describe a balloon-assisted double-lumen microcatheter technique to perform a controlled and tight coil packing of a vascular segment for vessel occlusion. This technique can be performed immediately after a test occlusion with the balloon kept in place and was, as illustrated in six cases, in our experience safe, straight forward to use and fast.

Therapeutic decision and management of aneurysmal subarachnoid haemorrhage based on computed tomographic angiography.

The purpose of this study was to evaluate the potential of high quality computed tomographic angiography (CTA) to replace digital subtraction angiography (DSA) in cases of ruptured saccular aneurysms and perform early surgical clipping or coiling on the basis of CTA alone. In a prospective study, 100 patients with aneurysmal subarachnoid haemorrhage (SAH) diagnosed by computed tomography underwent CTA. CTA revealed a total of 118 aneurysms including all ruptured aneurysms. A decision of direct surgical clipping, endovascular coiling or therapeutic abstention was made in 89 cases (89%) on the basis of CTA alone. Sixty-one direct surgical procedures were performed after CTA. Twenty-six cases underwent DSA for immediate endovascular treatment of the ruptured aneurysm. In 11 cases (11%), a DSA was performed prior to the therapeutic decision because of unclear aneurysm. Four cases were not treated because of initial poor clinical grade. The surgical findings were compared with CTA data and were considered accurate in all but one case. All patients underwent postoperative DSA within 10 days after SAH. The sensitivity and the specificity of CTA for the detection of all aneurysms, as compared with postoperative DSA, were 95.1 and 100%, respectively. A total of six unruptured aneurysms were missed initially, but were visible retrospectively on CTA in all but one case and were found in patients with multiple aneurysms in whom the ruptured aneurysm was detected by CTA. Current quality CTA allows reliable pretreatment planning for the majority of cases of aneurysmal subarachnoid haemorrhage and diminishes the pretreatment evaluation time critically. Complementary pretreatment DSA is required in situations where CTA characteristics of the ruptured aneurysm is unsatisfactory.

Spontaneous visual improvement in pituitary metastasis.

PURPOSE: To report spontaneous visual improvement in a patient with unilateral optic neuropathy due to pituitary metastasis. METHODS: Report of a case. RESULTS: A 54-year-old woman with a history of breast carcinoma lost vision in her right eye to 20/70 without any other symptoms. Six days later, vision spontaneously improved to 20/30. A pituitary mass compressing the right intracranial optic nerve was found on magnetic resonance imaging and the diagnosis of metastatic breast carcinoma was confirmed by biopsy. CONCLUSIONS: Spontaneous visual improvement can occur in the setting of compressive optic neuropathy by a solid mass.

Endovascular coiling compared with surgical clipping for the treatment of unruptured middle cerebral artery aneurysms: an update.

OBJECT: In 1999 we reported that 94% of unruptured middle cerebral artery (MCA) aneurysms managed prospectively between 1993 and 1997, according to a protocol favoring endovascular coiling, were best treated by surgical clipping. The goal of the current study was to delineate the most appropriate treatment option for unruptured MCA aneurysms today, considering the technical advances in imaging and in endovascular treatment. METHODS: 35 consecutive patients harboring 40 unruptured MCA aneurysms were treated between 1997 and December 2000. Patients with unruptured cerebral aneurysms are managed prospectively according to the same protocol as reported previously [1]: the primary treatment recommendation is endovascular packing with Guglielmi detachable coils (GDCs). Surgical clipping is recommended after failed attempt at coil placement or in the presence of angioanatomical features that contraindicate that type of endovascular therapy. RESULTS: One unruptured MCA aneurysm was treated by endovascular embolization, 37 unruptured MCA aneurysms were clipped, whereas 2 unruptured MCA aneurysms were trapped with simultaneous extracranial-intracranial revascularization. Postoperative angiography revealed complete exclusion of all aneurysms. Preservation of vascular permeability was demonstrated in all clip-reconstructed aneurysms, despite arterial branches frequently originating from the aneurysmal base. Cerebral revascularization of the distal MCA was successful in the 2 patients with giant aneurysms. None of the patients presented permanent disabling complications from the treatment of the unruptured MCA aneurysm. CONCLUSION: Despite major technical advances in imaging and in endovascular treatment of cerebral aneurysms, surgical clipping still is the most efficient treatment for unruptured MCA aneurysms at the beginning of the new millennium.

Intraorbital ophthalmic artery aneurysm associated with basilar tip saccular aneurysm.

We present a rare case of intraorbital ophthalmic artery aneurysm found incidentally, together with a ruptured aneurysm of the tip of the basilar artery. The intraorbital aneurysm was asymptomatic, and no treatment was offered. Angiographic control was recommended to detect any progression. Treatment may be indicated for documented enlargement or significant mass effect of the aneurysm.

Fluorodeoxyuridine improves imaging of human glioblastoma xenografts with radiolabeled iododeoxyuridine.

Use of radiolabeled nucleotides for tumor imaging is hampered by rapid in vivo degradation and low DNA-incorporation rates. We evaluated whether blocking of thymidine (dThd) synthesis by 5-fluoro-2'-deoxyuridine (FdUrd) could improve scintigraphy with radio-dThd analogues, such as 5-iodo-2'-deoxyuridine (IdUrd). We first show in vitro that coincubation with FdUrd substantially increased incorporation of [125I]IdUrd and [3H]dThd in the three tested human glioblastoma lines. Flow cytometry analysis showed that a short coincubation with FdUrd (1 h) produces a signal increase per labeled cell. We then measured biodistribution 24 h after i.v. injection of [125I]IdUrd in nude mice s.c. xenografted with the three glioblastoma lines. Compared with animals given [125I]IdUrd alone, i.v. preadministration for 1 h of 10 mg/kg FdUrd increased the uptake of [125I]IdUrd in the three tumors 4.8-6.8-fold. Compatible with previous reports, there were no side effects in mice observed for 2 months after receiving such a treatment. The tumor uptake of [125I]IdUrd was increased < or =13.6-fold when FdUrd preadministration was stepwise reduced to 1.1 mg/kg. Uptake increases remained lower (between 1.7- and 5.8-fold) in normal proliferating tissues (i.e., bone marrow, spleen, and intestine) and negligible in quiescent tissues. DNA extraction showed that 72-80% of radioactivity in tumor and intestine was bound to DNA. Scintigraphy of xenografted mice was performed at different times after i.v. injection of 3.7 MBq [125I]IdUrd. Tumor detection was significantly improved after FdUrd preadministration while still equivocal after 24 h in mice given [125I]IdUrd alone. Furthermore, background activity could be greatly reduced by p.o. administration of KClO4 in addition to potassium iodide. We conclude that FdUrd preadministration may improve positron or single photon emission tomography with cell division tracers, such as radio-IdUrd and possibly other dThd analogues.

Language representation in a patient with a dominant right hemisphere: fMRI evidence for an intrahemispheric reorganisation.

Studies have suggested that congenital left hemispheric (LH) frontal arteriovenous malformations (AVMs) are associated with an early transfer of language to right hemisphere (RH) frontal regions. The question remains whether such anatomofunctional reorganisation is due to RH compensatory abilities or to a general principle of lateral shift. In this study, we used fMRI language paradigms to investigate the case of a patient presenting aphasic symptoms following an haemorrhage due to a right frontal AVM. Prior to surgery, fMRI showed that language processing was confined to the RH, suggesting that language had not shifted during childhood from this congenitally dominant RH to the LH. After surgery, the patient presented severe aphasia that recovered to presurgical level within 70 days. At this time, fMRI showed that language tasks were still not associated with activations in the LH. These results suggest that the principles of early cerebral reorganisation after congenital lesions may differ in the RH and the LH. In addition, they support the idea that efficient restoration of language is achieved if a sufficiently large neuronal network is preserved around the lesion.

p73 is not mutated in meningiomas as determined with a functional yeast assay but p73 expression increases with tumor grade.

The p53 gene is normally wild type in meningiomas. Since all three members of the p53 gene family recognize the same DNA sequence, tumors containing wild type p53 could decrease transactivation of p53 target genes by mutating either p63 or p73. In meningiomas the most likely target is p73, because loss of heterozygosity of the chromosomal band containing p73 is the commonest genetic lesion in these tumors. To screen p73 for mutations we have developed a functional assay which tests the ability of p73 to activate transcription from a p53-responsive promoter in yeast. The assay correctly identified p73 mutants with mutations equivalent to hotspot mutations in p53, demonstrating that the assay can detect transcriptionally inactive p73. No mutations in p73 were identified in meningiomas. p73 RNA level was higher in more advanced tumors, but there was no correlation between the expression level of p73 and p21, a known p53 target gene. The yeast assay was also used to measure the intrinsic sensitivity of the p73 protein to mutagenesis. Like p53, p73 is exceptionally easy to inactivate as a transcription factor by point mutation. Taken together, these results indicate that p53 and p73 serve very different functions in tumors.

Developmental venous anomaly with an arteriovenous shunt and a thrombotic complication. Case report.

Developmental venous anomalies (DVAs) are common congenital variations of normal venous drainage that are known for their benign natural history. Isolated cases of symptomatic DVAs with associated arteriovenous (AV) shunts have recently been reported. The present case, in which thrombosis occurred in a DVA involving an AV shunt, raises intriguing questions regarding the clinical characteristics of these lesions and can be used to argue in favor of considering such lesions to be arteriovenous malformations (AVMs). A 39-year-old man presented with acute thrombosis in a complex system of anomalous hemispheric venous drainage, which included two distinct DVAs, one of which involved an AV shunt. The hemodynamic turbulences induced by a communication between shunted and normal venous outflows were the possible predisposing factor of the thrombosis. Follow-up angiographic and magnetic resonance images revealed complete recanalization of the thrombosed vessel and provided a thorough visualization of the particular angioarchitecture of the DVA. Acute thrombosis within a DVA with an AV shunt has not been reported previously and, thus, this case can be added to other reports of complications that arise in this particular type of DVA. The authors hypothesize that the presence of an AV shunt in a DVA is a risk factor for aggressive clinical behavior of the anomaly, rendering those lesions prone to complications similar to AVMs. Although no treatment can be offered, the presence of an AV shunt in a DVA warrants close follow-up observation because such lesions may represent a particular subtype of AVM and, therefore, may exhibit an aggressive clinical behavior.

Preoperative silk suture embolization of cerebral and dural arteriovenous malformations.

OBJECT: The aim of this study was to evaluate the use of silk sutures as a medical implant when applied for the embolization of cerebral and dural arteriovenous malformations (AVMs). The facility of surgery and the clinical significance of complications related to preoperative silk suture embolization were evaluated immediately after surgery and at long-term follow up. METHODS: Thirty-four patients harboring 29 cerebral and five dural AVMs underwent embolization in which silk alone or in association with other agents was used. Medical and radiological records obtained in these 34 patients were reviewed retrospectively. The cerebral AVMs were classified according to the Spetzler-Martin grading system and the dural AVMs to the Djindjian grading system. The facility of the resection and the adverse outcomes, including new neurological deficits, hemorrhage, and fever, as well as histopathological evidence of vessel inflammatory changes, were determined in each case. In all 23 surgical cases, the AVM could be easily manipulated and excised. New temporary neurological deficits occurred in three patients. A high Spetzler-Martin grade was not associated with a higher incidence of new neurological deficits. One delayed-onset hemorrhage was detected after embolization. Fever was present in 24% of the patients. No sign of significant vasculitis or perivascular inflammation was found on radiological or histopathological examination. CONCLUSIONS: Silk sutures are safe embolic agents especially for proximal occlusion of AVM feeding vessels. New permanent neurological deficits were not encountered in this series. Fever was considered to be a minor, temporary side effect of silk suture embolization.

Unlabelled iododeoxyuridine increases the cytotoxicity and incorporation of [1251]-iododeoxyuridine in two human glioblastoma cell lines.

Iododeoxyuridine (IUdR), labelled with radioiodines emitting Auger, alpha or beta- radiation, has been proposed as a therapeutic tool in the treatment of cancer. However, the low per cent incorporation in tumour cells and limited cytotoxicity are major obstacles for such an application. Using unlabelled IUdR as a modulator, we have studied the in vitro cytotoxicity of [125I]-IUdR in two human glioblastoma cell lines. Surprisingly, an enhanced cytotoxicity of [125I]-IUdR was observed in the presence of 0.3-10 microM concentrations of unlabelled IUdR in U251 glioblastoma cells and to a lesser extent in LN229 cells. The presence of unlabelled IUdR unexpectedly increased the incorporation of [125I]-IUdR in both cell lines. Thymidine competitively blocked the cytotoxic effects of combined unlabelled and [125I]-labelled IUdR in these cells and DNA-incorporation of radiolabelled IUdR.

The brain parenchyma is permissive for full antitumor CTL effector function, even in the absence of CD4 T cells.

Effective antitumor immune responses against cerebral malignancies have been demonstrated in several models, but precise cellular function of specific effector cells is poorly understood. We have explored this topic by analyzing the MHC class I-restricted T cell response elicited after implantation of HLA-CW3-transfected P815 mastocytoma cells (P815-CW3) in syngeneic mice. In this model, tumor-specific CTLs use a distinctive repertoire of TCRs that allows ex vivo assessment of the response by immunophenotyping and TCR spectratyping. Thus, for the first time in a brain tumor model, we are able to directly visualize ex vivo CTLs specific for a tumor-expressed Ag. Tumor-specific CTLs are detected in the CNS after intracerebral implantation of P815-CW3, together with other inflammatory cells. Moreover, despite observations in other models suggesting that CTLs infiltrating the brain may be functionally compromised and highly dependent upon CD4 T cells, in this syngeneic P815-CW3 model, intracerebral tumors were efficiently rejected, whether or not CD4 T cells were present. This observation correlated with potent ex vivo cytotoxicity of brain-infiltrating CTLs, specific for the immunodominant epitope CW3170-179 expressed on P815-CW3 tumor cells.