Treatment of giant intracranial aneurysms: long-term outcomes in surgical versus endovascular management.

Aneurysms with a major diameter > 25 mm are defined as giant intracranial aneurysms (GIAs). Different clinical, pathological, and radiological factors were revealed as playing a role in choosing the best strategy between surgical and endovascular approaches. Despite the improvement of both techniques, the efficacy and safety of these different management are still debated. We evaluated the differences in clinical and radiological outcomes of GIAs treated with surgical and endovascular techniques in a large retrospective mono-centric study. We compared aneurysm location, clinical, morphological features, treatment outcome, and complications on the ground of treatment technique. The final cohort consisted of 162 patients. All the patients were assigned on the ground of the type of eligible treatment: surgical (118 patients) and endovascular procedure (44 patients). The different treatment strategies were made through a multidisciplinary selection whereas clinical parameters, location, and morphologic features of the aneurysm were considered. The surgical group manifested a greater reduction in performance levels and neurological status in the post-operative phases than the endovascular group (p < 0.01) with a higher incidence of complications (p = 0.012) in contrast to a lower recurrence rate (p > 0.01). There is no significant difference in post-operative mortality and survival between surgical and endovascular groups. The surgical group manifested a higher incidence of complications after treatment. The endovascular group has a better post-operative outcome, but a higher risk of recurrence and the necessity of further treatment.

Effects of hispolon on glioblastoma cell growth.

Hispolon is a polyphenolic compound isolated from Phellinus linteus which exhibits antitumor activity. Here, we explored the effects of hispolon on human glioblastoma cells U87MG. Cell viability was examined by MTT assay. Growth was investigated by incubating cells with various concentrations of hispolon (25 and 50 µM) for 24, 48 or 72 h and daily cell count. Cell cycle and apoptosis assay were assessed by flow cytometry. Hispolon decreased cell viability in a dose- and time-dependent manner. The cell cycle distribution showed that hispolon enhanced the accumulation of the cells in G2/M phase. Hispolon decreased the expression of G1-S transition-related protein cyclin D4 but increased the expression of CDK inhibitor p21. Additionally, hispolon enhanced the expression of p53. Moreover, hispolon treatment was effective on U87MG cells in inhibiting cell viability and inducing cell apoptosis. Our results indicate that hispolon inhibits the cell viability, induces G2/M cell cycle arrest and apoptosis in glioblastoma U87MG cells, and p53 should play a role in hispolon-mediated antitumor activity.

Endoscope-assisted resection of calcified thoracic disc herniations.

PURPOSE: Resection of calcified thoracic disc herniations carries significant risks of neurological worsening, particularly in case of concomitant central location. Transthoracic approaches are a first-choice option to avoid spinal cord manipulation but entail drawbacks such as postoperative pain and the risk of bronchopulmonary complications. The purpose of this report is to describe a novel approach to resect calcified herniations, even centrally located, from a posterior perspective. METHODS: Unilateral lamino-arthrectomy is performed, uncovering few millimeters of the disc space beside the dura. Following discectomy and drilling of the vertebral endplates, an angled endoscope is introduced allowing resection of the calcified herniation through an anterior perspective. The spinal cord can now be decompressed with a no-touch technique. Each maneuver aimed at resecting the calcified mass up to the contralateral side can be done under visual control. RESULTS: The technique was used in two patients. The first was a 38-year-old man with a calcified mediolateral T9-T10 disc herniation and mild myelopathic symptoms. The second patient was a 73-year-old obese woman, with a T6-T7 central, calcified disc herniation and severe compression myelopathy. In both cases, complete decompression of the spinal cord could be achieved and rapid neurological recovery was observed postoperatively. No surgery-related complications were observed. CONCLUSIONS: The endoscope-assisted posterior approach afforded safe and complete resection of calcified discs. The technique is particularly useful for central disc herniations, where transthoracic approaches are normally deemed mandatory.

In vitro and in vivo effect of human lactoferrin on glioblastoma growth.

OBJECT: Human lactoferrin (HLF) is a natural protein with antitumor activity. The aim of this study was to investigate the effects of HLF alone and in combination with temozolomide (TMZ), a conventional chemotherapeutic, on human glioblastoma (GBM) cells. METHODS: The authors cultured fresh human primary cell lines NMD and FN and the continuous cell line U87MG to evaluate proliferation in the presence of HLF alone at different doses (1, 10, and 100 mg/ml, and 1 mg/ml) and in combination with TMZ. In in vivo experiments they assessed tumor size reduction in CD1 nude mice carrying an orthotopic GBM xenograft and orally treated with HLF. RESULTS: Lactoferrin causes growth inhibition in the NMD and FN primary cell lines and in the U87MG continuous cell line. This inhibition seemed to be modulated by the downregulation of cyclin D1 and D4. Western blot and fluorescence-activated cell sorting analysis showed inhibition of the cell cycle in G0/G1 and G2 phases. When administered in nude mice, HLF (60 mg/kg/day) decreased tumor size about 30%, as shown in both histological analyses and high-field brain MRI. Administration of HLF with TMZ enhanced the effect of chemotherapy both in vitro and in vivo. CONCLUSIONS: This study demonstrated that HLF can inhibit GBM cell growth, suggesting that this nontoxic substance may have a role in potentiating the effect of current TMZ treatment of GBM.

Results of a phase II study of Short-course Accelerated Radiation Therapy (SHARON) for multiple brain metastases.

OBJECTIVES: To assess the effectiveness of a SHort-course Accelerated RadiatiON therapy (SHARON) in the treatment of patients with multiple brain metastases. MATERIALS AND METHODS: A phase II clinical trial was designed. Eligibility criteria included patients with at least 3 brain metastases or metastatic disease in >3 organ systems, and Eastern Cooperative Oncology Group performance status of ≤3. Fifty patients were treated with whole brain radiotherapy at 18 Gy (4.5 Gy per fraction) in 2 days with a twice daily fractionation. The primary endpoint was the assessment of efficacy in terms of overall survival. RESULTS: Characteristics of the 50 enrolled patients were: male/female: 24/26; median age: 65 years (range, 45 to 80 y). Eastern Cooperative Oncology Group performance status was <3 in 42 patients (84%). Nineteen patients (38%) were considered to have recursive partitioning analysis class 3 disease. Grade 1-2 acute neurological (46%) and skin (24%) toxicities were recorded. Three patients (6%) experienced neurological grade 3 acute toxicity. With a median follow-up time of 6 months (range, 1 to 18 mo) 2 skin grade 1 late toxicities has been observed. Seventeen of 27 symptomatic patients showed an improvement or resolution of baseline symptoms (overall palliative response rate: 63.0%; 95% confidence interval, 36.6%-82.4%).Two-month overall survival was 86% (median survival time=7 mo). CONCLUSIONS: Short-course accelerated whole brain radiotherapy of 18 Gy in twice daily fractions for 2 consecutive days is tolerated and effective in terms of symptom relief and median survival time. These results justify a phase III comparison against the standard-of-care in this patient population (30 Gy in 10 fractions).

Intracranial hemangiopericytoma--our experience in 30 years: a series of 43 cases and review of the literature.

OBJECTIVE: Meningeal hemangiopericytoma (HPC) is a rare, aggressive central nervous system tumor that tends to invade locally and to metastasize, and has a high rate of recurrence. METHODS: This study presents a retrospective review of patients managed for intracranial HPC at Rome University Hospital. RESULTS: A total of 43 patients with intracranial HPC were treated from 1980 to 2010. Treatment and follow-up information was available for analysis on 36 patients. The median survival for all patients was 83.5 months after date of diagnosis, with 1-year, 5-year, and 10-year survival rates of 100%, 94.4%, and 72.2%, respectively. Eighteen patients (41.86%) had HPC recurrence. The median time until recurrence was 72.24 months, with 1-year, 5-year, and 10-year progression-free survival rates of 98%, 51%, and 29%, respectively. Five patients (11.62%) developed extracranial metastasis. Patients undergoing any form of adjuvant radiation treatment, including external beam radiotherapy, Gamma Knife radiosurgery, and/or proton beam therapy, had no longer median overall survival (OS) (178 vs. 154 months, respectively; P = .2); but did have a significantly improved recurrence-free interval (108 vs. 64 months; P = .04) compared with patients who did not undergo radiation treatment. Tumor characteristics associated with earlier recurrence included size ≥7 cm (log-rank, P < .05) and sinus invasion (log-rank, P < .05). CONCLUSIONS: Strategies combining adjuvant radiation with tumor resection seemed to hinder tumor progression, but had no effect on OS or the development of metastases. Greater extent of resection was associated with increased OS (log-rank, P < .05). Anaplastic HPC was associated with reduced OS and with reduced recurrence interval (log-rank, P < .05).

Functional cross talk between CXCR4 and PDGFR on glioblastoma cells is essential for migration.

Glioblastoma (GBM) is the most common and aggressive form of brain tumor, characterized by high migratory behavior and infiltration in brain parenchyma which render classic therapeutic approach ineffective. The migratory behaviour of GBM cells could be conditioned by a number of tissue- and glioma-derived cytokines and growth factors. Although the pro-migratory action of CXCL12 on GBM cells in vitro and in vivo is recognized, the molecular mechanisms involved are not clearly identified. In fact the signaling pathways involved in the pro-migratory action of CXCL12 may differ in individual glioblastoma and integrate with those resulting from abnormal expression and activation of growth factor receptors. In this study we investigated whether some of the receptor tyrosine kinases commonly expressed in GBM cells could cooperate with CXCL12/CXCR4 in their migratory behavior. Our results show a functional cross-talk between CXCR4 and PDGFR which appears to be essential for GBM chemotaxis.

Sacral Tarlov cyst: surgical treatment by clipping.

BACKGROUND: This study reports the anatomopathological classification of Tarlov cysts and the various treatment techniques described in the literature. METHODS: The authors present their patient series (19 cases) with a long follow-up (range 9 months to 25 years) treated by cyst remodeling around the root using titanium clips. RESULTS: The technique is effective in both avoiding cerebrospinal fluid leakage and resolving bladder dysfunction when urinary symptoms are incomplete and discontinuous. CONCLUSIONS: The clipping technique for Tarlov cysts is easy, valid, safe, rapid, and effective.

Rapamycin inhibits the growth of glioblastoma.

The molecular target of rapamycin (mTOR) is up-regulated in glioblastoma (GBM) and this is associated with the rate of cell growth, stem cell proliferation and disease relapse. Rapamycin is a powerful mTOR inhibitor and strong autophagy inducer. Previous studies analyzed the effects of rapamycin in GBM cell lines. However, to our knowledge, no experiment was carried out to evaluate the effects of rapamycin neither in primary cells derived from GBM patients nor in vivo in brain GBM xenograft. These data are critical to get a deeper insight into the effects of such adjuvant therapy in GBM patients. In the present study, various doses of rapamycin were tested in primary cell cultures from GBM patients. These effects were compared with that obtained by the same doses of rapamycin in GBM cell lines (U87Mg). The effects of rapamycin were also evaluated in vivo, in brain tumors developed from mouse xenografts. Rapamycin, starting at the dose of 10nm inhibited cell growth both in U87Mg cell line and primary cell cultures derived from various GBM patients. When administered in vivo to brain xenografts in nude mice rapamycin almost doubled the survival time of mice and inhibited by more than 95% of tumor volume.

A phase I study of short-course accelerated whole brain radiation therapy for multiple brain metastases.

PURPOSE: To define the maximum tolerated dose (MTD) of a SHort-course Accelerated whole brain RadiatiON therapy (SHARON) in the treatment of patients with multiple brain metastases. METHODS AND MATERIALS: A phase 1 trial in 4 dose-escalation steps was designed: 12 Gy (3 Gy per fraction), 14 Gy (3.5 Gy per fraction), 16 Gy (4 Gy per fraction), and 18 Gy (4.5 Gy per fraction). Eligibility criteria included patients with unfavorable recursive partitioning analysis (RPA) class>or=2 with at least 3 brain metastases or metastatic disease in more than 3 organ systems, and Eastern Cooperative Oncology Group (ECOG) performance status≤3. Treatment was delivered in 2 days with twice-daily fractionation. Patients were treated in cohorts of 6-12 to define the MTD. The dose-limiting toxicity (DLT) was defined as any acute toxicity≥grade 3, according to the Radiation Therapy Oncology Group scale. Information on the status of the main neurologic symptoms and quality of life were recorded. RESULTS: Characteristics of the 49 enrolled patients were as follows: male/female, 30/19; median age, 66 years (range, 23-83 years). ECOG performance status was <3 in 46 patients (94%). Fourteen patients (29%) were considered to be in recursive partitioning analysis (RPA) class 3. Grade 1-2 acute neurologic (26.4%) and skin (18.3%) toxicities were recorded. Only 1 patient experienced DLT (neurologic grade 3 acute toxicity). With a median follow-up time of 5 months (range, 1-23 months), no late toxicities have been observed. Three weeks after treatment, 16 of 21 symptomatic patients showed an improvement or resolution of presenting symptoms (overall symptom response rate, 76.2%; confidence interval 0.95: 60.3-95.9%). CONCLUSIONS: Short-course accelerated radiation therapy in twice-daily fractions for 2 consecutive days is tolerated up to a total dose of 18 Gy. A phase 2 study has been planned to evaluate the efficacy on overall survival, symptom control, and quality of life indices.

Lhermitte-Duclos disease presenting with positron emission tomography-magnetic resonance fusion imaging: a case report.

INTRODUCTION: Lhermitte-Duclos disease or dysplastic gangliocytoma of the cerebellum is an extremely rare tumor. It is a slowly enlarging mass within the cerebellar cortex. The majority of cases are diagnosed in the third or fourth decade of life. CASE PRESENTATION: We report the case of a 37-year-old Caucasian woman who underwent positron emission tomography-computed tomography with fluorine-18-fluorodeoxyglucose for evaluation of a solitary lung node. No pathological uptake was detected in the solitary lung node but the positron emission tomography-computed tomography of her brain showed intense tracer uptake, suggestive of a malignant neoplasm, in a mass in her left cerebellar lobe. Our patient had experienced two years of occipital headache and movement disorder. Subsequently, magnetic resonance imaging was performed with contrast agent administration, showing a large subtentorial mass in her left cerebellar hemisphere, with compression and dislocation of the fourth ventricle. Metabolic data provided by positron emission tomography and morphological magnetic resonance imaging views were fused in post-processing, allowing a diagnosis of dysplastic gangliocytoma with increased glucose metabolism. Total resection of the tumor was performed and histological examination confirmed the diagnosis of Lhermitte-Duclos disease. CONCLUSIONS: Our case indicates that increased uptake of fluorine-18-fluorodeoxyglucose may be misinterpreted as a neoplastic process in the evaluation of patients with Lhermitte-Duclos disease, but supports the usefulness of integrated positron emission tomography-magnetic resonance imaging in the exact pathophysiologic explanation of this disease and in making the correct diagnosis. However, an accurate physical examination and exact knowledge of clinical data is of the utmost importance.

Intracranial capillary hemangioma: a description of four cases.

OBJECTIVE: Capillary hemangiomas are benign vascular lesions involving the skin and soft tissues that commonly occur at birth or an early age. Intracranial capillary hemangiomas are extremely rare; only 14 cases have been reported the literature. CASE DESCRIPTION: We describe four patients with capillary hemangiomas. In two of these patients the lesions arose from the cavernous sinus. In the third patient, a large capillary hemangioma arising from the middle cranial fossa extended into the infratemporal fossa. The fourth patient had a left hemorrhagic temporoparietal capillary hemangioma. RESULTS: The first two patients underwent a partial resection, followed by radiotherapy. Local tumor control was achieved in both cases, as shown by the follow-up magnetic resonance imaging. In the third patient the lesion was subtotally removed after embolization. Radiotherapy, performed one year after surgery because of recurrence, allowed tumor control. In the fourth patient surgical removal was total and no adjuvant radiotherapy was required after surgery; follow-up magnetic resonance imaging did not show any recurrence at the one-year follow-up. CONCLUSION: Surgery is an option for symptomatic intracranial capillary hemangiomas. However, because partial removal is associated with a high recurrence rate, capillary hemangiomas that cannot be removed radically should be treated with radiotherapy, which offers the possibility of controlling lesion size and preventing tumor recurrence.

CXCL12-induced glioblastoma cell migration requires intermediate conductance Ca2+-activated K+ channel activity.

The activation of ion channels is crucial during cell movement, including glioblastoma cell invasion in the brain parenchyma. In this context, we describe for the first time the contribution of intermediate conductance Ca(2+)-activated K (IK(Ca)) channel activity in the chemotactic response of human glioblastoma cell lines, primary cultures, and freshly dissociated tissues to CXC chemokine ligand 12 (CXCL12), a chemokine whose expression in glioblastoma has been correlated with its invasive capacity. We show that blockade of the IK(Ca) channel with its specific inhibitor 1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole (TRAM-34) or IK(Ca) channel silencing by short hairpin RNA (shRNA) completely abolished CXCL12-induced cell migration. We further demonstrate that this is not a general mechanism in glioblastoma cell migration since epidermal growth factor (EGF), which also activates IK(Ca) channels in the glioblastoma-derived cell line GL15, stimulate cell chemotaxis even if the IK(Ca) channels have been blocked or silenced. Furthermore, we demonstrate that both CXCL12 and EGF induce Ca(2+) mobilization and IK(Ca) channel activation but only CXCL12 induces a long-term upregulation of the IK(Ca) channel activity. Furthermore, the Ca(2+)-chelating agent BAPTA-AM abolished the CXCL12-induced, but not the EGF-induced, glioblastoma cell chemotaxis. In addition, we demonstrate that the extracellular signal-regulated kinase (ERK)1/2 pathway is only partially implicated in the modulation of CXCL12-induced glioblastoma cell movement, whereas the phosphoinositol-3 kinase (PI3K) pathway is not involved. In contrast, EGF-induced glioblastoma migration requires both ERK1/2 and PI3K activity. All together these findings suggest that the efficacy of glioblastoma invasiveness might be related to an array of nonoverlapping mechanisms activated by different chemotactic agents.

Activity of hippocampal, amygdala, and neocortex during the Rey auditory verbal learning test: an event-related potential study in epileptic patients.

OBJECTIVE: Previous evidence in epileptic subjects has shown that theta (about 4-7Hz) and gamma rhythms (about 40-45Hz) of hippocampus, amygdala, and neocortex were temporally synchronized during the listening of repeated words successfully remembered (Babiloni et al., 2009). Here we re-analyzed those electroencephalographic (EEG) data to test whether a parallel increase in amplitude of late positive event-related potentials takes place. METHODS: Intracerebral electroencephalographic (EEG) activity had been recorded in five subjects with drug-resistant temporal lobe epilepsy, undergoing pre-surgical evaluation. During the recording of the intracerebral EEG activity, the subjects performed a computerized version of the Rey auditory verbal learning test (RAVLT). They heard the same list of 15 common words for five times. Each time, immediately after the listening of the list, the subjects were required to repeat as many words as they could recall. RESULTS: We found that late positive event-related potentials (ERPs) peaking at about 350ms post-stimulus in amygdala, hippocampus, and occipital-temporal cortex had a higher amplitude during the listening of the repeated words that were subsequently recalled than for those that were not recalled. CONCLUSIONS: Late positive ERPs reflect a functional mechanism implemented in a human brain network spanning amygdala, hippocampus, and occipital-temporal cortex which is at the basis of the memorization processes of verbal materials. SIGNIFICANCE: This ERP component is a promising neuromarker of successful memorization of repeated words in humans.

High-grade intramedullary astrocytomas: 30 years' experience at the Neurosurgery Department of the University of Rome "Sapienza".

OBJECT: The goal in this study was to review a series of patients who underwent surgical removal of intramedullary high-grade gliomas, focusing on the functional outcome, recurrence rates, and technical problems continually debated in neurosurgical practice. METHODS: Between December 1976 and December 2006, 22 patients underwent removal of intramedullary high-grade gliomas. Lesions were located in the cervical spinal cord in 12 patients, and in the thoracic cord in 10. RESULTS: Histological examinations showed 10 Grade III astrocytomas and 12 glioblastomas. Only 2 of the 22 high-grade astrocytomas could be completely removed. The clinical postoperative status worsened in 14 patients (63.6%), was unchanged in 7 patients (31.8%), and there was 1 case of intraoperative death (4.5%). None of the 22 patients showed improvement in their neurological status postoperatively. In this series, excluding the 1 intraoperative death, all patients died of progression of the malignancy. CONCLUSIONS: Surgical treatment did not ameliorate the postoperative neurological status; instead, in the majority of cases, it prompted a worsening of the deficit. Radiotherapy and chemotherapy have a little influence on the length of survival. In this series, multimodality treatment of intramedullary high-grade astrocytomas has been shown to increase length of survival without improving the neurological status.

Role of stereotactic radiosurgery and fractionated stereotactic radiotherapy for the treatment of recurrent glioblastoma multiforme.

Glioblastoma multiforme (GBM) is a devastating malignant brain tumor characterized by resistance to available therapeutic approaches and relentless malignant progression that includes widespread intracranial invasion, destruction of normal brain tissue, progressive disability, and death. Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) are increasingly used in patients with recurrent GBM to complement traditional treatments such as resection, conventional external beam radiotherapy, and chemotherapy. Both SRS and fSRT are powerful noninvasive therapeutic modalities well suited to treat focal neoplastic lesions through the delivery of precise, highdose radiation. Although no randomized clinical trials have been performed, a variety of retrospective studies have been focused on the use of SRS and fSRT for recurrent GBMs. In addition, state-of-the-art neuroimaging techniques, such as MR spectroscopic imaging, diffusion tensor tractography, and nuclear medicine imaging, have enhanced treatment planning methods leading to potentially improved clinical outcomes. In this paper the authors reviewed the current applications and efficacy of SRS and fSRT in the treatment of GBM, highlighting the value of these therapies for recurrent focal disease.

Cavernous sinus meningiomas: retrospective analysis and proposal of a treatment algorithm.

OBJECTIVE: Today, meningiomas with primary or, more commonly, secondary involvement of the cavernous sinus remain a surgical challenge. Anatomic research on cadaver specimens, together with the advances made in cranial base and microvascular surgery over the past 2 decades, have made it possible to completely resect lesions within the cavernous sinus. However, the technical complexity of some procedures, coupled with the current availability of less-invasive therapeutic options, makes the rate of complications related to surgical extirpation of intracavernous meningiomas unacceptably high, especially regarding permanent neurological morbidity and mortality. Currently, indications, timing, and multimodal treatments with surgery and radiotherapy represent the main topics of discussion concerning these lesions. METHODS: One hundred forty-seven patients underwent surgery between 1985 and 2003. The patients were retrospectively divided into 2 groups according to the type of surgical treatment: group A (open sinus surgery) and group B (closed sinus surgery). The mean follow-up time was 9.7 years. RESULTS: Early postoperative morbidity and permanent postoperative morbidity showed significant differences between the groups. At long-term follow-up, we found no statistical differences in the incidence of recurrences and progressions. Only patients treated with postoperative radiation therapy (81.5%) showed clinicoradiological stability. CONCLUSION: Growth control and preservation of neurological functions are the primary goals in the treatment of cavernous sinus meningiomas. In most cases, surgery and radiosurgery alone do not reach the primary goals, and unresolved issues remain. Therefore, we have developed a treatment algorithm as a guide to the best therapeutic options for the most common presentations of the disease.

Expression of aryl hydrocarbon receptor (AHR) and AHR-interacting protein in pituitary adenomas: pathological and clinical implications.

Germline mutations of the aryl hydrocarbon receptor (AHR)-interacting protein (AIP) gene confer a predisposition to pituitary adenomas (PA), usually in the setting of familial isolated PA. To provide further insights into the possible role of AIP in pituitary tumour pathogenesis, the expression of AIP and AHR was determined by real-time RT-PCR and/or immunohistochemistry (IHC) in a large series of PA (n=103), including 17 with AIP mutations (AIP(mut)). Variable levels of AIP and AHR transcripts were detected in all PA, with a low AHR expression (P<0.0001 versus AIP). Cytoplasmic AIP and AHR were detected by IHC in 84.0 and 38.6% of PA respectively, and significantly correlated with each other (P=0.006). Nuclear AHR was detected in a minority of PA (19.7%). The highest AIP expression was observed in somatotrophinomas and non-secreting (NS) PA, and multivariate analysis in somatotrophinomas showed a significantly lower AIP immunostaining in invasive versus non-invasive cases (P=0.019). AIP expression was commonly low in other secreting PA. AIP immunostaining was abolished in a minority of AIP(mut) PA, with a frequent loss of cytoplasmic AHR and no evidence of nuclear AHR. In contrast, AIP overexpression in a subset of NS PA could be accompanied by nuclear AHR immunopositivity. We conclude that down-regulation of AIP and AHR may be involved in the aggressiveness of somatotrophinomas. Overall, IHC is a poorly sensitive tool for the screening of AIP mutations. Data obtained on AHR expression suggest that AHR signalling may be differentially affected according to PA phenotype.

Hippocampal, amygdala, and neocortical synchronization of theta rhythms is related to an immediate recall during rey auditory verbal learning test.

It is well known that theta rhythms (3-8 Hz) are the fingerprint of hippocampus, and that neural activity accompanying encoding of words differs according to whether the items are later remembered or forgotten ["subsequent memory effect" (SME)]. Here, we tested the hypothesis that temporal synchronization of theta rhythms among hippocampus, amygdala, and neocortex is related to immediate memorization of repeated words. To address this issue, intracerebral electroencephalographic (EEG) activity was recorded in five subjects with drug-resistant temporal lobe epilepsy (TLE), under presurgical monitoring routine. During the recording of the intracerebral EEG activity, the subjects performed a computerized version of Rey auditory verbal learning test (RAVLT), a popular test for the clinical evaluation of the immediate and delayed memory. They heard the same list of 15 common words for five times. Each time, immediately after listening the list, the subjects were required to repeat as many words as they could recall. Spectral coherence of the intracerebral EEG activity was computed in order to assess the temporal synchronization of the theta (about 3-8 Hz) rhythms among hippocampus, amygdala, and temporal-occipital neocortex. We found that theta coherence values between amygdala and hippocampus, and between hippocampus and occipital-temporal cortex, were higher in amplitude during successful than unsuccessful immediate recall. A control analysis showed that this was true also for a gamma band (40-45 Hz). Furthermore, these theta and gamma effects were not observed in an additional (control) subject with drug-resistant TLE and a wide lesion to hippocampus. In conclusion, a successful immediate recall to the RAVLT was associated to the enhancement of temporal synchronization of the theta (gamma) rhythms within a cerebral network including hippocampus, amygdala, and temporal-occipital neocortex.

Three-dimensional computed tomography angiography in presurgical planning for treatment of infratentorial dural arteriovenous fistulas.

Dural arteriovenous fistulas (DAVFs) with pure leptomeningeal drainage may be cured by simple interruption of their venous side. This report illustrates the cases of 3 patients undergoing surgery for fistulas classified as Borden Type III, involving the posterior cranial fossa. Preoperatively, the surgical anatomy of these lesions was investigated with 3D reformatting of multislice CT angiography, in addition to conventional angiography. Reformatted images clarified the surgical anatomy of the malformation. Reconstructing both the osseous and the vascular structures and simulating the surgical orientation allowed localization of the dural takeoff point of the DAVF's drainage, showing its relationship with osseous landmarks. Precise localization of the DAVF's drainage may help in choosing the most direct and effective approach to treat the malformation. The reported cases could be treated with a standard retrosigmoid exposure, avoiding the need for more complex cranial base approaches.