Internal auditory canal metastasis.

Metastasis of the inner auditory canal is a really rare event. Clinically, it usually presents with rapid worsening cranial nerve palsy. Authors present a review of the literature reporting clinical features, radiological findings, intraoperative aspects of an illustrative case. A 56-year-old female patient presented with a peripheral facial nerve palsy. MRI showed two left p-fossa tumors whose one into the inner canal. Rapid worsening of facial damage despite corticosteroid treatment and the possibility to remove both tumors in the same surgical step suggested authors to operated on the patient. Intraoperatively, inner canal tumor looked totally involving the VII-VIII nerve complex so surgical extirpation was only partially feasible. Posterior wall drilling of the meatus was performed which improved facial palsy. Leptomeningeal spinal seeding occurred and spinal irradiation was performed. The case highlights the importance of maintaining a high degree of awareness of the auditory canal metastasis in patients with a previous history of malignancy who develop a rapid progressive peripheral VII nerve palsy. Furthermore, our case and literature data suggest that inner canal metastasis is a distinct entity from temporal bone and ponto-cerebellar angle metastasis on the base of the peculiarity of clinical features, prognosis, therapeutic strategies. In fact, inner canal metastases usually arise in patients apparently cured, and they imply a better prognosis even if with an higher risk of leptomeningeal seeding. Moreover, surgery rarely allows the removal of the lesion, also if symptoms relief may be achieved, as in our case.

Neurosurgical treatment of von Hippel-Lindau-associated hemangioblastomas: benefits, risks and outcome.

AIM: Von Hippel-Lindau (VHL) disease is a genetic syndrome predisposing to central nervous system (CNS) hemangioblastomas and several lesions in many organs. The cases of all VHL individuals operated on in the Neurosurgical Unit of Padua Hospital since year 2000 were reviewed in order to define which features lead to surgical treatment and to examine surgical outcome during postoperative follow-up. METHODS: The authors evaluated 20 VHL subjects (7 males and 13 females, age at surgery 32+/-10 years) who underwent 28 operations in order to remove 48 CNS hemangioblastomas and 1 endolymphatic sac tumor. Among the 49 resected lesions, 21 (42%) were cerebellar, 9 (18%) at brainstem, 19 (38%) spinal (7 cervical, 6 dorsal, 6 at cone-cauda level), and 1 (2%) endolymphatic sac tumor in the petrous bone. Patients were graduated according to Karnofsky Performance Status (KPS) at admission, at discharge and during the last follow up visit. Genetic testing revealing the presence of a VHL disease-causing mutation was a prerequisite for inclusion in the study. RESULTS: Nineteen individuals (95%) were symptomatic. Symptomatic hemangioblastomas were associated with a cyst or a syrinx in 22/27 circumstances (81%). Total removal, as confirmed by postoperative magnetic resonance imaging (MRI), was achieved in all but one lesion. Following surgery, at follow-up (38+/-20 months), patients improved their neurological status in 75% of cases, 20% remained stable and 5% worsened; 16 patients (80%) are able to carry on normal activity with or without minor symptoms, 3 patients require some grade of assistance, 1 patient died because of bronchopneumonia. CONCLUSION: VHL-associated hemangioblastomas generally affect a young adult population and can be successfully removed, either when symptomatic, or when they reach a critical volume. Microsurgery of hemangioblastomas has a favourable impact on survival and quality of life of VHL patients, although it is strongly influenced by preoperative conditions. Transient surgical complications are possible, particularly with brainstem and spinal cord hemangioblastomas.

Metastatic oligodendrogliomas: a review of the literature and case report.

Oligodendroglioma cells are detectable in the cerebro-spinal fluid in up to 14% of patients [10] and cerebellar and/or spinal cord involvement is a well known phenomenon [3]. Distant spread of oligodendroglioma is exceptional, probably due to the presence of the blood-brain barrier, the absence of lymphatic vessels and the short survival of patients. A review of the worldwide literature yielded 32 previously reported examples since 1951 to the present (Tab1e 1). This review was performed using NCBI-PubMed and "oligodendroglioma, oligodendrogliomas, metastatic, metastasis, metastases, extraneural", in different combinations, as key words and reviewing the bibliography of the consequent selected articles. New therapeutic approaches are prolonging the overall survival of patients with primitive brain tumours and in particular of those with high grade oligodendroglioma which is a chemo-sensitive disease. A longer overall survival could increase the risk of extracranial dissemination of gliomas that in the future might become a less rare clinical complication.

Peroxisome proliferator-activated receptor gamma in the human pituitary gland: expression and splicing pattern in adenomas versus normal pituitary.

Pituitary adenomas are slow-growing tumours arising within the pituitary gland. If secreting, they give rise to well-known syndromes such as Cushing's disease or acromegaly; when hormonally inactive, they come to clinical attention often with local mass effects or pituitary deficiency. Peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear hormone receptor with a key role in fat and glucose metabolism, but also involved in several neoplasia, has recently been detected in pituitary adenomas. In the present study, we evaluated the occurrence and splicing profile of PPARgamma in 43 cases of pituitary adenoma of different subtypes and compared it to 12 normal pituitary glands. By real-time polymerase chain reaction, PPARgamma was expressed as much in adrenocorticotrophic hormone (ACTH)-secreting and ACTH-silent adenomas as in controls, with a moderate underexpression in somatotrophinomas and prolactinomas and overexpression in 54% of nonfunctioning pituitary adenomas (NFPA). There was no apparent qualitative change in the splicing profile of pathological pituitary glands, nor was the presence of specific isoforms with dominant negative effects against PPARgamma detected. Western blotting revealed similar expression levels in the different subgroups of pituitary adenomas and normal glands. Immunohistochemistry confirmed PPARgamma expression in approximately one-half of analysed samples. The intra- and intergroup differences observed in pituitary adenomas may represent new elements in the process of understanding the different clinical responses of Cushing's and Nelson patients to PPARgamma-ligand treatment. Moreover, the higher level of PPARgamma expression detected in the NFPA subgroup may suggest its possible role as a molecular target in these pituitary adenomas, paving the way for investigations on the effectiveness of treatment with thiazolidinediones in such patients.

Haemorrhagic presentation of low-grade glioma in adults.

Intracranial bleeding is rare in patients with low-grade gliomas, above all in adult population. We reviewed the literature of such cases and reported another case of a haemorrhagic low-grade glioma in a 54-year-old woman presenting with a left hemiparesis. Computer tomography (CT) images showed a right basal ganglia haemorrhage with no mass effect. Vascular malformations were ruled out by angiography. Eighteen fluoro-fluoro deossiglucosio (18F-FDG) positron emission tomography (PET/CT) showed a large hypometabolic area corresponding to the lesion. We waited for patient's improvement. Late magnetic resonance images revealed a low-grade glioma at the bleeding site. Tumour was removed and histopathologic examination revealed a WHO grade II mixed glioma. The authors emphasize that this evidence has to be kept in mind since it has important therapeutic implications.

A multidrug combination designed for reversing resistance to BCNU in glioblastoma multiforme.

BACKGROUND: Nitrosoureas constitute the main resource of chemotherapy for glioblastoma. However, because of chemoresistance, which is intrinsic or rapidly acquired after the first administration of chemotherapy, there have been few improvements in survival. Because O(6)-alkylguanine-DNA alkyltransferase (AGT) is the main target for increasing cell sensitivity to the nitrosoureas, we postulated that preexposure to other alkylating agents might increase the therapeutic index of the nitrosoureas by saturating all the copies of AGT present in the tumor cells. OBJECTIVE: To investigate the response rate, toxic effects, time from start of chemotherapy to progression of disease or exit from the study for any reason (TTP), and progression-free survival at 6 months (PFS-6) associated with a multidrug combination that could reverse resistance to carmustine (BCNU) through AGT depletion. METHODS: We conducted a phase 2 study of patients with glioblastoma at first relapse or progression after surgery and standard radiotherapy. Patients were treated with 100 mg/m(2) of procarbazine on days 1 to 5, 80 mg/m(2) of BCNU on days 3 to 5, and 1.4 mg/m(2) of vincristine on day 3 every 8 weeks. RESULTS: Fifty-eight patients were enrolled in the study, and all were assessable for response and toxic effects. Six patients (10.3%) had a complete response, 11 (19%) had a partial response, and 17 (29.3%) had stable disease. The median TTP was 4.8 months; 42.3% of patients had PFS-6, and 15.4% had PFS at 12 months. Response to chemotherapy was the only significant prognostic factor for TTP. Neutropenia was grade 3 in 8.6% of patients and grade 4 in 5.2% of patients, and thrombocytopenia was grade 3 in 17.2% of patients and grade 4 in 12% of patients; hepatic and pulmonary toxic effects were grade 3 in 5.2% and 8.6% of patients, respectively. CONCLUSION: This regimen proved active in chemotherapy-naive patients with recurrent glioblastoma even though toxic effects were substantial.

Preoperative embolization of arteriovenous malformations with polylene threads: techniques with wing microcatheter and pathologic results.

The technique with a wing microcatheter system and the pathologic aspects of 11 cerebral arteriovenous malformations (AVMs) surgically resected after embolization with polylene threads are reported. Embolization was performed once in eight patients and twice in three patients. Resected AVMs were submitted both to routine hematoxylineosin examination and to immunohistochemical workup in order to detect the type of immunologic response to thread emboli. In nine cases, 50% or more of the nidus was obliterated by the embolization. After embolization two patients developed reversible neurologic deficits. Pathologic specimens of resected AVMs demonstrated no vascular necrosis; however, a moderate inflammatory response could be seen, characterized by the presence of both mononuclear cells and foreign-body giant cells, associated with the absence of polymorphonuclear infiltrates. A granulomatous fibrotic process was identified that was present from the first month after embolization. Immunohistochemistry indicated that the immunologic response to thread emboli was cell-mediated, not humoral. Embolization with the wing microcatheter with the use of polylene threads proved to be a safe and efficient system of embolization, as a preoperative procedure. Polylene threads are a nontoxic and biocompatible material that can be used as an embolic agent for brain AVMs.

Role of computed tomography in the management of vasospasm after subarachnoid hemorrhage.

The role of computed tomography (CT) in the management of vasospasm from subarachnoid hemorrhage was evaluated in 242 consecutive cases with CT performed within 7 days after hemorrhage. Only 20% of these cases did not show a detectable subarachnoid hemorrhage on CT. Subsequent angiograms showed vessel narrowing in 56% of the cases; associated clinical deterioration was noted in 34% of the cases. On later CT, clear ischemic areas were detected in 20% of the cases. A strict correlation between the amount of cisternal blood and the subsequent development of vasospasm was observed: although absent or thin cisternal depositions were rarely associated with vasospasm, consistent or thick depositions were frequently linked to vasospasm (72% of the cases) and to ischemic disturbances (51% of the cases), as well as to clear ischemic areas on later CT (30% of the cases). Regarding the morphology of the cisternal blood collection, the risk of developing vasospasm was at its lowest (42%) for depositions only in the frontal interhemispheric fissure and was at its highest (79%) for depositions in multiple cisterns. The site of cisternal deposition corresponded closely to the area of ischemia on later CT. The persistence of subarachnoid blood more than 72 hours after hemorrhage probably increases the risk of vasospasm, although our data are not conclusive. The definition of a CT scan "at risk" for vasospasm--based on the previous findings--gives practical advantages: proper selection of patients in regard to timing of operation, closer observation and the possibility of prophylactic treatment in patients "at risk," and more adequate evaluation of different therapeutic modalities for vasospasm. With regard to the last point, the incidence of vasospasm was not statistically different between two groups of patients uniformly "at risk": the first group submitted to early operation and the second awaiting operation.

The relevance of anatomic and hemodynamic factors to a classification of cerebral arteriovenous malformations.

Potential prognostic anatomic and hemodynamic factors were evaluated in 248 patients with cerebral arteriovenous malformations (AVMs), all treated by direct microsurgical removal. The size of each AVM was calculated by its volume, obtained by the multiplication of the three AVM diameters by 0.52. A surgical classification of AVM location (in 11 groups) is proposed. Types of feeders and of drainage were classified as superficial or deep; the extent of the drainage system was classified according to a four-degree scale. The mean flow velocity in the main AVM feeder, detected using transcranial Doppler ultrasonography, was used as an indirect measure of AVM shunt flow in a small number of patients (n = 29). AVM volume was a very important prognostic factor: the incidence of hyperemic complications and the morbidity and mortality rate were significantly higher when the volume of the lesion was greater than 20 cm3 (P less than 0.0001 for hyperemic complications; P less than 0.001 for permanent morbidity and mortality). The incidence of hyperemic complications and the morbidity rate were higher in AVMs in rolandic, inferior limbic, and insular locations than in AVMs in other locations. As for other anatomic factors: a) the presence of deep feeders significantly increased the incidence of hyperemic complications, as well as the morbidity and mortality rate; b) the presence of deep drainage significantly increased permanent morbidity only; c) the extension of the venous system was significantly related to the development of hyperemic complications, and to morbidity and mortality. Transcranial Doppler examination showed that mean flow velocities greater than 120 cm/s in the main feeder were associated with a significantly higher rate of postoperative hematomas and transient deficits. A classification of cerebral AVMs that takes into account AVM volume and location, the type of feeders, the extent of the drainage system, and the main feeder flow velocity is suggested.

Treatment of cerebral arteriovenous malformations with a combination of preoperative embolization and surgery.

Forty-nine patients with cerebral arteriovenous malformations (AVMs) were treated with preoperative embolization followed by resection using a microsurgical approach. In 27 patients, the AVM was located in an eloquent area; in 32 patients, the volume of the AVM was over 20 cm3. Preoperatively, flow-directed embolization was performed in 10 patients (28 procedures), selective embolization with threads was performed in 35 patients (46 procedures), and a combination of flow-directed and selective embolization was performed in 4 patients (12 procedures). The percentage of reduction of the AVM volume averaged 36% after embolization. Five minor complications (transient neurological deficits, in 2 cases associated with ischemic areas on the CT scan) were observed after embolization. The interval between the last embolization and surgery was as follows: within 10 days in 7 patients; between 11 and 20 days in 3 patients; between 21 and 30 days in 10 patients; between 31 and 60 days in 11 patients; and 2 months later in 18 patients. The efficacy of this combined treatment (embolization plus surgery) was evaluated by the incidence of hyperemic complications and the clinical outcome. Hyperemic complications occurred more frequently in patients with an AVM volume greater than 20 cm3. When compared with flow-directed embolization, selective embolization was linked with decreased bleeding during surgery; postoperatively, the incidence of cerebral edema was also lower. Clinical outcome was better after selective embolization, with no occurrence of major deficits and no mortality. When the percentage of reduction of the AVM volume after embolization was 40% or more, the incidence of intraoperative hyperemic complications was lower; moreover, new permanent deficits were never observed in patients with this volume reduction. A retrospective clinical comparison of two groups of patients with similar AVM volumes (greater than 20 cm3)--those given combined treatment (n = 32) versus those treated by direct surgery alone (n = 27)--showed that intraoperative bleeding appeared to decrease in patients treated by embolization; the incidence of postoperative hyperemic complications was not different in the two groups. New major deficits and deaths were less frequent in patients treated by embolization (P = 0.05 for the incidence of major deficits); postoperative epilepsy was also less common in these patients. In conclusion, combined treatment with selective preoperative embolization and direct surgery may help the neurosurgeon in the treatment of large, high-flow AVMs, reducing the risks connected with their surgical removal.

Surgical problems in the treatment of aneurysms of the posterior circulation.

BACKGROUND: Despite the recent multidisciplinary achievements, surgery for posterior circulation aneurysms remains challenging. Sac dimensions and fundus projection are highly variable and independent factors, which can determine, the operative field being deep and restricted, in some case the failure of the procedure. Other factors the surgeon must cope with are the relationships between aneurysm and surrounding arteries, cranial nerves (oculomotor nerve mainly) and bone structures. Due to the esiguity of the operative field a complete dissection of the sac can be achieved frequently only after the clipping when, by the way, the clip position must be verified in order to avoid perforants closure. Aim of this paper is to perform a retrospective study regarding patients harbouring a posterior circulation aneurysm treated in a public health environment. METHODS: Our experience resides on 78 consecutive cases (whose 37 of the basilar artery and 37 with other localizations) successfully clipped by the same surgeon (senior author: RS); 4 additional aneurysms were only explored (whose 3 originated from the basilar artery). The clinical charts of the basilar apex cases were reviewed, the angiographic and intraoperative findings were correlated to the GOS (Glasgow Outcome Scale). RESULTS: The fundus projection in the basilar apex cases was the main risk factor accounting for a 50% mortality rate in the antero-posterior direction cases. CONCLUSIONS: Posterior circulation aneurysms are intimidating vascular malformations even nowadays; in the future improvements in the endovascular technique could provide an effective alternative to an open surgery approach.

Deep controlled hypotension with sodium nitroprusside in the surgical treatment of intracranial arterial aneurysms.

The authors report 73 cases of intracranial arterial aneurysms operated on under deep controlled hypotension--i.e. hypotension below 60 mmHg of systolic arterial pressure (s.a.p.)--. Deep hypotension was induced by Sodium Nitroprusside (SNP). No problems were encountered in order to reach or to maintain deep hypotension. SNP showed to be an easy hypotensive agent, without toxicity at the recommended dosage. Fifty-nine patients were operated on between 40 and 25 mmHg of s.a.p. In 55 patients deep hypotension lasted for 30 minutes or more, reaching 2 hours in 3 patients. Surgical results were excellent, in regard either to the control of bleeding, either to the dissection of the aneurysm. Clinical results were evaluated by comparison with 146 patients operated on under normal pressure (group of control); no complications were clearly related to deep hypotension per se. However, the authors stress the risks of deep hypotension in early surgery, due to the possible association to vascular spasm.

Microsurgical treatment of juxtapeduncular angiomas.

Five patients harboring juxtapeduncular angiomas were all treated by a direct microsurgical approach. Anatomic considerations, angiographic data on the feeding arteries, and related anomalies are discussed. The operating microscope and deep hypotension were very useful for the complete removal of these lesions, which were approached in most cases by a "backward" technique. Diffuse bleeding from the paraventricular area was difficult to handle. There were no postoperative deaths. At follow-up examination, 1 patient had hemiparesis and hemianopia, 2 patients had mild visual field defects, and 2 patients had normal neurological examinations. All but one of the patients have resumed their previous occupations. It is concluded that microsurgery constitutes the best treatment for these malformations.

Direct microsurgical approach to aneurysms of the internal carotid bifurcation.

In this report, a series of 21 aneurysms of the internal carotid bifurcation, all treated with a direct microsurgical approach, is discussed. A classification of these aneurysms, according to angiographic and anatomical considerations, is proposed. The surgical treatment of aneurysms of the internal carotid bifurcation is discussed, emphasizing the importance of avoiding damage to perforating vessels. One of the patients presented in this report died from postoperative vascular spasm and three had transient disturbances in the postoperative course. All surviving patients recovered completely.

Posterior inferior cerebellar artery aneurysm in the fourth ventricle: acute surgical treatment.

A case of an aneurysm of the posterior inferior cerebellar artery lying in the fourth ventricle is reported. The patient was surgically treated within a few hours after the onset of the subarachnoid hemorrhage by a microsurgical technique using direct exclusion of the aneurysm by a clip. The patient recovered completely following the operation.

Intracranial hematomas following aneurysmal rupture: experience with 309 cases.

Three hundred and nine consecutive cases of intracranial hematomas due to aneurysmal rupture--representing 34% of the total number of patients with aneurysms observed in a 12-year period--were evaluated; of these, 211 were submitted to computed tomography scan. Hematomas were present on admission in 71% of patients and occurred at rebleeding in 29%. Ruptured middle cerebral artery aneurysms caused an intracranial hematoma more frequently than aneurysms in other locations. Ventricular hematomas were frequently observed--especially at rebleeding--in cases with anterior communicating artery aneurysms. Basal ganglia hematomas were detected in eight cases with internal carotid bifurcation aneurysms and in three with middle cerebral artery aneurysms. Subdural hematomas were observed in 32 cases, mainly due to ruptured middle-cerebral-artery and internal-carotid-artery aneurysms. As for clinical evolution, a rapid deterioration was observed in 39% of cases and a chronic course in 46%; a subacute deterioration was far less frequent. Delayed deterioration from vasospasm was observed in 8% of cases, and appeared to be related to the amount of subarachnoid bleeding associated with the hematoma. One hundred and forty-two patients were submitted to surgical treatment (evacuation of hematoma together with exclusion of aneurysm); deep coma, poor medical condition, stabilized neurological disability, or combinations of these factors accounted for the high number of patients not operated upon. Regardless of treatment, 24% of patients showed good results and 58% died. Presence of a large hematoma, ventricular hemorrhage, and shift of the ventricles represented significant risk factors, associated with a poor prognosis. A comparison between two groups of patients admitted within 3 days of hemorrhage--47 operated on early, and 149 with delayed treatment--showed that better results were achieved by early operations, especially for cases in Hunt's grades IV and V.

[Surgical treatment of supratentorial arteriovenous malformations]. / Terapia chirurgica delle malformazioni artero-venose sopratentoriali.

The authors present their experience in the surgical treatment of supratentorial arteriovenous malformations. A few morphological data on the structure of these lesions are described, owing to their surgical relevance. The principles influencing the operative decisions--such as the age of the patient, his clinical history, the site and size of the malformation--are discussed. The operative strategy adopted for the removal of these lesions are articulated in various points: the organization for a long-lasting procedure, the use of the operative microscope and bipolar coagulation, a wide surgical exposure, a particular care for dural feeders and a wide arachnoidal opening, the trial of hypotension, the early closure of deep feeders, the saving of draining veins for as long as possible, the dissection along the sulci and into the white matter, the saving of functional arteries and accessory veins, the techniques adopted against paraventricular bleeding and hemorrhage from venous sinusoids, the coagulation of deep vessels, a particular care for possible AV fistulae under the main drainage, the "backward" technique, the "rosary-like" coagulation, a particular care for a possible division of the malformation into partitions. Particular surgical problems can occur in large AVMs, with diffuse hyperemia and hemorrhages due to anomalous perfusion of the tissue adjacent to the AVM; in these cases, controlled hypotension appears useful. The problems faced in the surgical approach to AVMs located in specific areas--such as cortical AVMs with deep extension, cortico-basal and cortico-interhemispheric AVMs, callosal AVMs, AVMs of the insula and basal ganglia, intra- and para-ventricular AVMs, juxtapeduncular and juxtasplenial AVMs--are finally discussed.

BMP2 sensitizes glioblastoma stem-like cells to Temozolomide by affecting HIF-1α stability and MGMT expression.

Glioblastoma multiforme (GBM) is the most common brain tumour, characterized by a central and partially necrotic (i.e., hypoxic) core enriched in cancer stem cells (CSCs). We previously showed that the most hypoxic and immature (i.e., CSCs) GBM cells were resistant to Temozolomide (TMZ) in vitro, owing to a particularly high expression of O6-methylguanine-DNA-methyltransferase (MGMT), the most important factor associated to therapy resistance in GBM. Bone morphogenetic proteins (BMPs), and in particular BMP2, are known to promote differentiation and growth inhibition in GBM cells. For this reason, we investigated whether a BMP2-based treatment would increase TMZ response in hypoxic drug-resistant GBM-derived cells. Here we show that BMP2 induced strong differentiation of GBM stem-like cells and subsequent addition of TMZ caused dramatic increase of apoptosis. Importantly, we correlated these effects to a BMP2-induced downregulation of both hypoxia-inducible factor-1α (HIF-1α) and MGMT. We report here a novel mechanism involving the HIF-1α-dependent regulation of MGMT, highlighting the existence of a HIF-1α/MGMT axis supporting GBM resistance to therapy. As confirmed from this evidence, over-stabilization of HIF-1α in TMZ-sensitive GBM cells abolished their responsiveness to it. In conclusion, we describe a HIF-1α-dependent regulation of MGMT and suggest that BMP2, by down-modulating the HIF-1α/MGMT axis, should increase GBM responsiveness to chemotherapy, thus opening the way to the development of future strategies for GBM treatment.