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Objective Pituitary neuroendocrine tumours (PitNET)s can be aggressive, thus presenting local invasion, postsurgical recurrence and/or resistance to treatment, responsible for significant morbidity. The study aimed at identifying prognostic factors of postsurgical outcome using data-driven classification of patients.Design Retrospective observational study.Methods Clinicopathological and radiological data of patients with PitNET treated via endoscopic endonasal surgery were collected. Tumour recurrence/progression and progression-free survival were assessed by classification tree analysis (CTA) and Kaplan-Meier curves, respectively. Histological subtype, cavernous/sphenoid sinus invasion, mitosis, Ki-67, p53, Trouillas' grading, degree of tumour exeresis and postsurgery disease activity were also evaluated.Results A total of 1066 (466 gonadotroph, 287 somatotroph, 148 lactotroph, 157 corticotroph and 8 thyrotroph) tumours were included; 21.7% invaded the cavernous/sphenoid sinus. Based on Trouillas' classification, 64.3% were grade 1a, 14.2% 1b, 16.1% 2a, and 5.4% 2b; 18.3% had >2/10 HPF mitoses, 24.9% had Ki-67 >= 3%; 15.8% were positive for p53. Exeresis was radical in 81.2% of the cases. Median follow-up was 59.2 months. At last evaluation, 79.4% of the patients were cured; 20.6% had disease persistence, controlled by medical treatment in 18.3% of them. Disease recurrence/progression was recorded in 10.9% of the cases. CTA identified 5 distinct patient subgroups with different risk of disease recurrence/progression. Grade 2 of the Trouillas' grading, >2/10 HPF mitoses, Ki-67 >= 3%, p53 protein expression (P < .001), tumour invasion (P = .002) and ACTH-subtype (P = .003) were identified as risk factors of disease recurrence/progression.Conclusions The combined evaluation of Trouillas' grading, proliferation indexes and immunohistochemistry appears promising in the prediction of surgical outcome in PitNET.

Aims De-differentiated chordoma is an uncommon and incompletely characterised aggressive neoplasm. Only a few cases originating from the skull base have been reported. Methods and results All consecutive cases of skull-base de-differentiated chordomas treated surgically in a referral centre from January 1990 to June 2019 were retrospectively evaluated to assess peculiar pathological, radiological and clinical features. Patient data were retrieved from paper and electronic records. Six cases (two male, four female; mean age at surgery = 46 years, range = 35-64), treated surgically at our institution were identified. Transformation to de-differentiated chordomas occurred after radiation therapy in three cases (mean = 13.6 years after treatment, range = 5-25), two during tumour progression, while one was de-novo. Magnetic resonance imaging and surgical examination revealed the presence of two different tumour components, corresponding to the conventional and de-differentiated portion on histological examination. The de-novo case presented a PIK3CA mutation. DNA methylation analysis revealed consistent epigenetic changes in TERT, MAGEA11 and UXT. Prognosis was poor, as five of six patients died after surgery and radiation therapy, with a mean overall survival of 29 months (range = 11-52). Conclusions Skull-base de-differentiated chordomas are extremely rare and aggressive neoplasms with characteristic magnetic resonance imaging, surgical and histological features. Therefore, an early and accurate histological diagnosis is of paramount relevance. Molecular analysis appears promising to define mechanisms involved in tumour de-differentiation.

The evaluation of the isocitrate dehydrogenase (IDH) mutation status in the glioma decision-making process has diagnostic, prognostic and therapeutic implications. The aim of this study was to evaluate whether conventional magnetic resonance imaging (MRI) and apparent diffusion coefficient (ADC) can noninvasively predict the most common IDH mutational status (R132H) in GIII-astrocytomas and the overall survival (OS). Hence, twenty-two patients (9-F, 13-M) with a histological diagnosis of GIII-astrocytoma and evaluation of IDH-mutation status (12-wild type, 10-mutant) were retrospectively evaluated. Imaging studies were reviewed for the morphological feature and mean ADC values (ADCm). Statistics included a Fisher&rsquo, s exact test, Student&rsquo, s t-test, Spearman&rsquo, s Test and receiver operating characteristic analysis. A p &le, 0.05 value was considered statistically significant for all the tests. A younger age and a frontal location were more likely related to mutational status. IDH-wild type (Wt) exhibited a slight enhancement (p = 0.039). The ADCm values in IDH-mutant (Mut) patients were higher than those of IDH-Wt patients (p &lt, 0.0004). The value of ADC &ge, 0.99 &times, 10&minus, 3 mm2/s emerged as a &ldquo, cut-off&rdquo, to differentiate the mutation state. In the overall group, a positive relationship between the ADCm values and OS was detected (p = 0.003, r = 0.62). Adding quantitative measures of ADC values to conventional MR imaging could be used routinely as a noninvasive marker of specific molecular patterns.

The association of cavernous malformations and developmental venous anomalies (DVA) is well known, but the presence of arterial fistulous connection with the main venous collector has been reported in the literature only once. We report the unusual case of a hemorrhagic cavernous angioma associated with DVA characterized by a fine arterial supply to the main venous collector. During surgery, after the excision of the cavernous angioma, few small arterial feeders were found entering the main channel of the venous developmental anomaly. The presence of an arterial fistulous connection with the main venous collector of a DVA may be a possible mechanism involved in a higher bleeding potential of cavernous angioma.

Patient with surgically treated right temporo-occipito-parietal glioblastoma multiforme. Postoperative follow-up performed early (24 hours and 2 weeks) with MR morphologic sequences.

To assess outcomes and predictors of early and long-term remission in patients with Cushing’s disease (CD) due to ACTH-secreting adenomas treated via endoscopic endonasal approach (EEA). This is a retrospective study. Consecutive patients operated for CD from 1998 to 2017 in an Italian referral Pituitary Center were enrolled. Clinical, radiological, and histological data at enrollment and follow-up were collected. 151 patients (107 F) were included; 88.7% were naive for treatment, 11.3% had been treated surgically and 11.2% medically. At pre-operative magnetic resonance imaging (MRI), 35 had a macroadenoma and 80 a microadenoma, while tumor was undetectable in 36 patients. Mean age at surgery was 41.1 ± 16.6 years. Diagnosis was confirmed histologically in 82.4% of the cases. Patients with disease persistence underwent second surgery and/or medical and/or radiation therapy. Mean follow-up was 92.3 ± 12.0 (range 12–237.4) and median 88.2 months. Remission rate was 88.1% after the first surgery and 90.7% at last follow-up. One patient died of pituitary carcinoma. Post-surgical cortisol drop (p = 0.004), tumor detection at MRI (p = 0.03) and size

Background: The endoscopic endonasal opening of the optic canal has been recently proposed for tumors with medial invasion of this canal, such as tuberculum sellae meningiomas. Injury of the ophthalmic artery represents a dramatic risk during this maneuver. Therefore, the aim of this study was to analyze the endoscopic endonasal anatomy of the precanalicular and canalicular portion of this vessel, discussing its clinical implication. Methods: The course of the ophthalmic artery was analyzed through five endoscopic endonasal dissections, and 40 nonpathological consecutive MRAs were reviewed. Results: The ophthalmic artery arises from the intradural portion of the supraclinoid internal carotid artery, in 93 % of cases about 1.9 mm (range: 1–3) posterior to the falciform ligament. At the entrance into the optic canal, the ophthalmic artery is located infero-medially to the optic nerve in 13 % of cases. In 50 % of these cases the artery moves infero-laterally along its course, remaining in a medial position in the others. In cases with an non medial entrance of the ophthalmic artery, it runs infero-lateral to the optic nerve for its entire canalicular portion, with just one exception. Conclusion: The endoscopic endonasal approach gives a direct, extensive and panoramic view of the course of the precanalicular and canalicular portion of the ophthalmic artery. Dedicated high-field neuroimaging studies are of paramount importance in preoperative planning to evaluate the anatomy of the ophthalmic artery, reducing the risk of jeopardizing the vessel, particularly for those uncommon cases with an infero-medial course of the artery.

Objective: Pituitary macroadenomas (PAs) are usually defined as benign intracranial tumors. However, they may present local aggressive course. High Ki67 labelling index (LI) values have been related to an aggressive tumor behavior. A recent clinicopathological classification of PA based on local invasiveness and proliferation indexes, divided them in groups with different prognosis. We evaluated the utility of conventional MRI (cMRI) and diffusion-weighted imaging (DWI), in predicting the Ki67- LI according the clinicopathological classification. Methods: 17 patients (12 M and 5 F) who underwent surgical removal of a PA were studied. cMRI features, quantification of T1W and T2W signal intensity, degree of contrast uptake (enhancement ratio, ER) and apparent diffusion coefficient (ADC) values were evaluated by using a 3 T scan. Statistics included Mann–Whitney test, Spearman’s test, and receiver operating characteristic analysis. A value of p ≤ 0.05 was considered significant for all the tests. Results: Negative correlations were observed between Ki-67 LI, ADCm (ρ = - 0.67, p value = 0.005) and ER values (ρ = −0.62; p = 0.008). ER values were significantly lower in the proliferative PA group (p = 0.028; p = 0.017). ADCm showed sensitivity and specificity of 90 and 85% respectively into predict Ki67-LI value. A value of ADCm ≤0, 711 x 10–6 mm2 emerged as a cut-off of a value of Ki67-LI ≥ 3%. Conclusion: Adding quantitative measures of ADC values to cMRI could be used routinely as a non-invasive marker of specific predictive biomarker of the proliferative activity of PA. Advances in knowledge: Routinely use of DWI on diagnostic work-up of pituitary adenomas may help in establish the likely biological aggressive lesions.

The spectrum of corticotroph cell adenomas is very wide. Though rarely, silent corticotroph cell adenomas (SCA) may transform into corticotroph cell adenomas associated with Cushing's disease (CD). The aim of the study was to investigate the role of prohormone convertase 1/3 (PC1/3) in the transformation of SCA into CD. We reviewed the records of 1259 consecutive endoscopic endonasal procedures for pituitary adenomas from 1998 to 2013. Of these, 132 were CD and 44 were SCA. During the follow-up, three patients with SCA showed a clear transformation from SCA into CD and underwent surgery once again to remove the recurrent tumour. The PC1/3 expression was analysed by both immunohistochemistry and quantitative real time-polymerase chain reaction (qRT-PCR) in primary and recurrent tumours. The immunohistochemical PC1/3 expression was negative or weak in the three patients in the initial phase of SCA, while a strong expression was observed in the majority of neoplastic cells in tissue specimens obtained from the same three patients at the time of recurrence as CD. The immunohistochemical PC1/3 expression showed a strict correlation with the PC1/3 levels obtained by qRT-PCR. In 14 cases of SCA with no change of phenotype during the follow-up, the immunohistochemical PC1/3 expression was low and strictly associated with the level of PC1/3 obtained by qRT-PCR both in primary (14/14 cases) and in recurrent tumours (4/4 cases). Our study provides insight into the crucial role of the PC1/3 protein in the transformation of phenotype from SCA to CD.

Gliomas are the most common tumor type in the central nervous system (CNS), they account more than 70 % of all brain tumors, and of these, glioblastoma is the most frequent and malignant histologic type. The total incidence of primary CNS tumors is approximately 18.7 per 100,000 person in the United States and 7 per 100,000 worldwide. Diffuse infiltrating gliomas are the second most common primary central nervous system neoplasm [1].

The evaluation of the brain with magnetic resonance imaging can be divided essentially into two parts, morphological and functional study. Standard morphological study provides information about the anatomy of the brain tissue, the cerebrospinal fluid spaces, the skull, the arterial and venous blood vessels; it can also be completed with acquisitions after administration of contrast agent. Functional studies include diffusion weighted imaging (DWI), perfusion weighted imaging (PWI), spectroscpy. Parallel imagin is a new technique wich ensure faster acquisition.

Background: The most appropriate management of recurrent glioblastoma is still controversial. In particular, the role of surgery at recurrence remains uncertain. Patients & methods: From our Institutional data warehouse we analyzed 270 consecutive patients who received second surgery for recurrent glioblastoma, to assess survival after second surgery, and to evaluate prognostic factors. Results: Complete resection was found in 128 (47.4%) and partial resection in 142 patients (52.6%). Median survival from second surgery was 11.4 months (95% CI: 10.0–12.7). Multivariate analysis showed that age (p = 0.001), MGMT methylation (p = 0.021) and extent of surgery (p < 0.001) are associated with better survival. Conclusion: A complete resection should be the goal for second resection and younger age and MGMT methylation status might be considered in the selection of patients.

We report the clinical description of an Italian patient with c.638A>G mutation in exon 5 of EIF2B2 gene and a very slow progressive Vanishing White Matter disease phenotype. Infact, in relation to her causative mutation, our patient had an unusual early onset and long course. Furthermore, other than standard MRI examination and spectroscopy study, we report DWI and ADC maps and FA maps reconstruction from DTI in order to describe brain tissue degeneration in vanishing white matter disease.

PURPOSE: To assess the role of high sensitivity next-generation sequencing (NGS) of CTNNB1 for the diagnosis of adamantinomatous craniopharyngiomas (aCPs) and of BRAF for that of papillary CPs (pCPs) in routinely processed surgical samples of nonadenomatous sellar lesions. METHODS: Forty-five cases of patients operated for nonadenomatous masses of the sellar region between 2004 and 2014 were retrieved from the files of the Anatomic Pathology unit of the Bellaria Hospital in Bologna, Italy. BRAF and CTNNB1 mutation status was analyzed by NGS in samples smaller than 1 cm(3) and histological re-evaluation was performed on all cases. RESULTS: CTNNB1 mutation analysis showed a sensitivity of 86.7 % and a specificity of 96.2 % for the diagnosis of aCPs. The specificity increased to 100 % considering that in one case, initially classified as a non-CP lesion (xanthogranuloma), the identification of a CTNNB1 S47R lead to histological re-evaluation and reclassification of the lesion as aCP. BRAF mutation analysis had a sensitivity of 76.9 % and a specificity of 96.4 % for the diagnosis of pCPs. The specificity increased to 100 % considering that in one case, initially classified as a Rathke cyst, the identification of BRAF V600E lead to histological re-evaluation and reclassification of the lesion as pCP. CONCLUSIONS: This study confirms the diagnostic relevance of the molecular alterations recently identified in aCPs and pCPs and shows how the identification of BRAF and CTNNB1 mutations can be instrumental for the proper classification of samples that contain limiting amounts of diagnostic lesional tissue.

OBJECT Adrenocorticotropic hormone (ACTH) adenomas have been recognized as a more aggressive and invasive subtype of pituitary adenomas. An additional and clinically relevant peculiarity of these tumors is their ability to modify their clinical expression from a silent form to Cushing disease or vice versa. The aim of this study was to review a series of patients with pituitary adenomas and analyze the clinical implications of the transformation of clinical expression in 5 cases that showed this phenomenon. METHODS The authors retrospectively reviewed a series of patients with pituitary adenoma and collected clinical, biohumoral, and neuroradiological data of those who presented with a transformation from silent ACTH adenomas to functioning tumors or vice versa. In all the cases, preoperative assessment consisted of brain MRI, ophthalmological examination, and complete baseline endocrinological investigation. In patients with clinical and/or biochemical findings suspicious for Cushing syndrome, a low-dose dexamethasone suppression test was performed to rule in or out this diagnosis. Endocrinological evaluations were repeated 1 month after surgery, 3 months after surgery, and every 6 months or annually thereafter. Ophthalmological evaluations and brain MRIs were repeated after 3 months and then every 6 or 12 months thereafter. RESULTS Five patients (2 men and 3 women) included in this series had corticotropic tumors that showed transformation from an endocrinologically silent form to manifest Cushing disease and vice versa. The mean age at presentation was 40 years (range 18–51 years). In 3 of these patients, a transformation from silent to functioning ACTH adenoma with manifest Cushing disease occurred. In 1 patient, the authors observed the transition from a functioning to a silent adenoma with spontaneous resolution of hypercortisolism. Another patient's silent adenoma “shifted” to a functioning adenoma and then regressed back to a silent form with spontaneous resolution of Cushing disease. This patient again developed hypercortisolism, which finally resolved spontaneously. In this series, the transformation occurred after a mean of 3.5 years (range 6 months to 7 years). The shift from an ACTH-silent to a functioning adenoma was observed in 9% of the ACTH-silent adenomas in this series (4 of 44 cases), and the spontaneous remission of Cushing disease to a silent corticotroph cell adenoma occurred in 1.5% of cases of this series (2 of 132 functioning ACTH adenomas). At follow-up (mean 107 months; range 60–177 months), cortisol levels were within normal limits in all 5 cases. However, 1 patient required Gamma Knife radiosurgery and eventually adrenalectomy for disease control to be achieved. CONCLUSIONS The ability of silent ACTH adenomas to transform their secretion pattern poses a challenge for neurosurgeons and endocrinologists. Because the transformation is often unexpected, the clinical and biochemical data can be underestimated. Furthermore, this bizarre and unpredictable postoperative tumor behavior can lead to misinterpretation of clinical and endocrinological outcomes. Even if these cases are very rare, they are not anecdotal in large series. Thus, ACTH adenomas require careful biohumoral and neuroradiological follow-up to detect possible transformations.

Capillary telangiectasia is one of four forms of cerebral vascular malformations consisting of an area of dilated capillaries like a small petechial patch on the brain surface. The lesions are located mainly in the pons and cerebellum. We describe a case of diffuse capillary telangiectasia of the brain in a patient presenting with epilepsy who underwent morphological and function investigation using a 3T MR system.

A General Electric 3 Tesla Signa Excite system was installed in the Neuroradiology Unit of Bellaria Hospital, Bologna in February 2004. In line with current legislation, we designed a clinical research project to assess the practical impact of the new device on the investigation of brain tumours, the pituitary gland, rare neurological diseases, epilepsy, multiple sclerosis and Parkinson's disease. We describe our preliminary anecdotal findings in the study of brain tumours and the potential impact of 3 T imaging on the preparation and management of neurosurgical candidates. One decisive result to emerge is that the greater awareness of the risks and difficulties entailed in surgical resection help the neurosurgeon establish a more clear-cut relationship with patients on seeking their informed consent. By understanding and accepting the risks involved, we hope to curb the increasing number of legal disputes caused by surgical complications.

We describe two patients with extracerebral tumours histologically diagnosed as a metastasis with focal necrosis (case 1) and a meningioma with microcystic features (case 2), examined by proton magnetic resonance spectroscopy. Tumour metabolism did not fit literature reports as lipids were not detected in the metastasis but were found in the meningioma whose in vitro spectrum also showed metabolic abnormalities. This discrepancy may be due to the technique adopted in case 1 and the small amount of tumour necrosis, but it is difficult to account for in case 2. Some explanations are offered but long-term follow-up scans will establish whether the abnormal metabolic features indicative of a negative prognosis are confirmed by the patient's evolution. The cases described do not necessarily call other literature reports into question, but warrant caution in establishing a diagnosis on the basis 1HMRS findings. Spectrum acquisition techniques need to be standardized and short TE measurements are more reliable than those made with long TE.

We describe our experience at the Neuroradiology Service, Bellaria Hospital, Bologna, using three-dimensional time-of-flight magnetic resonance angiography (3D TOF MRA) with Maximum Intensity Projection reconstructions without gadolinium administration in 50 asymptomatic patients with saccular cerebral aneurysms following microcoil embolization. 3D TOF MRA follow-up was done one, three and six months and one year after treatment. The first MRA was compared with the angiogram obtained immediately after treatment and served as a reference for subsequent MRA monitoring. Angiographic follow-up was only undertaken in some patients, when a flow signal was present in the coil mesh or neck region or in the aneurysmal sac, and in relation to the degree of occlusion obtained by embolization. Eight out of the 50 patients underwent redo embolization after MRA disclosed recanalization confirmed by angiography. 3D TOF MRA was fast, straightforward and very useful in the short and long-term follow-up of patients after embolisation, proving a first choice method with a good correlation between the reference angiogram and MRA findings. 3D TOF MRA was also valid in the diagnosis of clinically significant findings confirmed by angiography in all cases, thereby selecting patients requiring further diagnostic investigation by angiography and possible redo embolization.

The theme of this year's 40thCongress of the American Society of Neuroradiology was 3 Tesla magnetic resonance.For many years, research into the use of magnetic resonance systems with 3 T magnets mainly focused on spectroscopy and functional magnetic resonance. More recent studies also used 3 T magnets for MR diagnosis, trying to optimize sequences for both anatomic imaging and for MR angiography and diffusion on the basis of protocols currently adopted with 1.5 T magnets1–3.The use of higher magnetic fields improves the signal/noise ratio and the chemical-shift sensitivity thereby enhancing spatial resolution (supported by the higher signal/noise ratio) and increasing the reliability of spectroscopy and functional MR imaging.The major technical problems encountered with 3 T systems are the increased number of artefacts due to magnetic sensitivity and chemical shift, the increase in tissue heating potential and the longer T1 longitudinal relaxation times.The main advantages of high magnetic field resonances are the higher signal/noise ratio, greater spectra dispersion, improved image resolution, faster acquisition times and greater sensitivity to differences in magnetic susceptibility. The drawbacks include a lower signal/noise ratio in relation to artefacts caused by magnetic susceptibility, longer T1 relaxation times, shorter T2 and T2* relaxation times, convergent tissue relaxation times, increased absorption of RF energy and a more inhomogeneous B1 signal.The advantages and limitations of higher magnetic field magnets have already been encountered at each stage in the development of MR technology. Once again, the best strategies need to be devised for the use of these new systems. Briefly, the increased signal produced by high field magnets (3 T) offers different advantages. In conventional diagnosis, the spatial resolution of the image is improved or acquisition times shortened, or when contrast is poor with current techniques as in functional MR or spectroscopy. Even the increase in artefacts due to magnetic susceptibility and chemical shift can be exploited advantageously. For example, the enhanced magnetic susceptibility produces a greater loss of signal intensity in sequences with gadolinium bolus perfusion, thereby improving assessment of brain haemodynamics and tissue vitality for a rational selection of candidates for stroke therapy and surgery.Studies were presented from different stroke centres in the United States using protocols comprising sequences for conventional anatomical investigation, weighted diffusion sequences, MR angiography and bolus perfusion.Image quality was equivalent or superior to that obtained with 1.5 T systems, especially angiographic sequences which were improved and faster with easier identification of the occluded branch. It was also demonstrated that the examination can be performed while the patient is receiving an infusion of thrombolytic drugs with real time monitoring of the pharmaceutical effect on the thrombosis.A group of researchers then presented their findings studying patients with an 8T MR system23–25. Exposure to such a high magnetic field was well tolerated and the study focused on evaluation of the small cerebral vessels exploiting sensitivity differences in blood oxygenation as deoxyhaemoglobin is paramagnetic and the effected of magnetic susceptibility exaggerated by such a high field. Using inhomogeneous local fields with gradient-echo images together with the signal/noise ratio of an 8 T system, minute cerebral vessels with a diameter of around 200 micron could be visualized.What emerged from the Congress presentations was that we can no longer be satisfied with the MR systems in use today when examinations which are currently long and cumbersome can be carried out more quickly, often with real time results and much shorter processing times. The impression was that the 1.5 T MR systems most of us use will soon be as obsolete as the 0.5 T systems and neuroradiologists' work will be increasingly shifted from morphological investigation to functional analysis, entailing new expertise.My only concern is the exposure of patients to such high magnetic fields, fearing the biological effects, especially when follow-up examinations have to be repeated. I hope that patients' welfare will not be disregarded in the search for ever greater morphological detail and that the new systems will be used when their true worth is of real benefit.

Magnetic Resonance Spectroscopy visible mobile lipids are considered important markers in the diagnosis of human cancer and are thought to be closely involved in various aspects of tumour transformation, such as cell proliferation, necrosis, apoptosis, hypoxia and drug resistance. A method allowing the straightforward identification of the lipid classes contributing to the mobile lipids in human malignant tissues is highly advisable. Ex vivo High Resolution Magic Angle Spinning Magnetic Resonance Spectroscopy was done directly on human cerebral, renal and colorectal malignant tissue specimens. A diffusion edited sequence, based on stimulated echo and bipolar gradient pulses, was used to characterize molecules with low diffusion rates, arising from mobile lipid components. Cholesterol, triglycerides and phosphatidylcholine are simultaneously detected and all contribute to the mobile lipid resonances present in malignant glioma and clear cell renal carcinoma tissue specimens spectra. On the contrary, papillary cell renal carcinoma spectrum is predominated by phosphatidylcholine resonances and that of colorectal adenocarcinoma is characterized by signals arising from triglycerides. Ex vivo diffusion edited High Resolution Magic Angle Spinning Magnetic Resonance Spectroscopy, done on intact tissue, is a powerful analytical tool to obtain a simple and immediate identification of mobile lipid components. This can offer a significant contribution to better understanding their involvement in cancer tissues. Furthermore, ex vivo high resolution spectroscopic measurements allow to improve the interpretation of in vivo Magnetic Resonance spectra, increasing its clinical potentiality.

BACKGROUND: RANO criteria, which evaluate both contrast enhancement and T2/FLAIR alterations, have been recently defined, but no prospective validation exists. We examined the radiological data of patients with recurrent glioblastoma treated with bevacizumab (BEV) or fotemustine (FTM) in the randomized phase II AVAREG-ML25739 (EUDRACT 2011-001363-46) trial. METHODS: All MRIs of the pts have been evaluated (BEV/FTM: 59/32) accordingly with RANO and Macdonald's criteria, both locally and centrally. RESULTS: 223 MRIs were analyzed. Concordance between RANO and Macdonald criteria was found in 96.3% of cases at local evaluation and in 95.5% at central revision. Concordances between local and central assessments were 72.5% with RANO criteria and 71.1% with Macdonald's criteria. At local evaluation, pts treated with BEV had a disease control rate (DCR = CR/PR/SD) of 0.75 (95%CI: 0.62-0.85) with RANO criteria, and 0.76 (95%CI: 0.63-0.86) with Macdonald criteria, vs 0.59 (95%CI: 0.41-0.76) and 0.63 (95%CI: 0.44-0.79) with FTM. Central evaluation showed a DCR of 0.80 (95%CI: 0.68-0.90) both with RANO and Macdonald criteria for pts treated with BEV vs 0.50 (95%CI: 0.32-0.68)with FTM. In the BEV arm, only 6.8% of patients showed an increase of T2/FLAIR without T1 contrast enhancement. CONCLUSIONS: After 4 years from RANO proposal, we showed that there is a good concordance of disease evaluation in recurrent glioblastoma pts treated either with BEV or FTM in academic centers.

The optimal end point for phase II studies for recurrent glioblastoma (GBM) is unclear and a matter of debate. Moreover, data about post-progression survival (PPS) after the first disease progression in GBM patients treated according to EORTC 26981/22981/NCIC CE.3 trial are limited. The aim of this study was to evaluate the PPS in GBM patients. The analysis was made with a database on 1,006 GBM patients followed prospectively between 06/2005 and 06/2010. Eligibility criteria for the study were: age ≥ 18 years; PS: 0-2; chemotherapy given at disease progression after RT/TMZ. 232 patients (mean age 52 years, range 18-77 years) were enrolled. The median PFS following second line chemotherapy (PFS2) was 2.5 months (95 % CI 2.1-2.9) and the rate of patients free of progression at 6 months (PFS2-6 mo), was 21.6 % (95 % CI 16.3-26.9 %). The median PPS was 8.6 months (95 % CI 7.4-9.8), PPS rates were: PPS-6: 66 % (95 % CI 60.3-72.9 %), PPS-9: 48.2 % (95 % CI 41.5-54.9 %) and PPS-12: 31.7 % (95 % CI 25.2-38.2 %). PPS in unselected patients treated with alkylating agents is about 8 months. PPS rates could be of interest as an end point in future studies in recurrent GBM.

Unfortunately, the affiliation of the author name, Antonella Bacci, was incorrectly listed as Antonella Bacci(1) instead of Antonella Bacci(3), and the affiliations were incorrectly listed as (1) Department of Neurosurgery, IRCCS Neurological Research Hospital; Bologna, Italy - (2) Section of Pathology "M. Malpighi", Bellaria Hospital, Azienda USL of Bologna, Bologna, Italy instead of (1) Department of Neurosurgery, (3) Department of Neuroradiology, IRCCS Neurological Research Hospital; Bologna, Italy. (2) Section of Pathology "M. Malpighi", Bellaria Hospital, Azienda USL of Bologna, Bologna, Italy in the original publication of this paper.

Introduction The International Classification of Headache Disorders classifies ophthalmoplegic migraine (OM) under “cranial neuralgias and central causes of facial pain.” OM is diagnosed when all the following criteria are satisfied: At least two attacks fulfilling criterion B. Migraine-like headache accompanied or followed within four days of its onset by paresis of one or more of the III, IV and/or VI cranial nerves. Parasellar orbital fissure and posterior fossa lesions ruled out by appropriate investigations. In children the syndrome is rare and magnetic resonance (MR) shows strongly enhancing thickened nerve at the root entry zone (REZ). Method The authors review the literature focusing on pathogenesis theories. Results The authors suggest that ischemic reversible breakdown of the blood-nerve barrier is the most probable cause of OM and to include MR findings in the hallmarks of the disease. Conclusion OM is the same disease in adulthood and childhood, even if in adults the MR imaging findings are negative. In the authors’ opinion, OM should be classified as migraine.

La studio neuroradiologico dell'idrocefalo nell'epoca dei trattamenti chirurgici endoscopici si arricchisce di nuovi quesiti e di nuovi segni.Se la TC mantiene la sua validità nella prima diagnosi di idrocefalo e nello studio delle complicanze immediate dei trattamenti endoscopici, perde il ruolo preminente che aveva nei controlli post-operatori a medio e lungo termine.La RM è l'esame di scelta in fase prechirurgica, per la pianificazione dell'intervento endoscopico, con lo studio dell'anatomia della regione del III ventricolo. Lo stesso discorso vale per i controlli post-chirurgici delle terzoventricolostomie, vista la maggiore importanza del dato funzionale della pervietà della stomia rispetto al semplice dato morfologico della variazione della volumetria ventricolare.Gli studi quantitativi con sequenze specifiche per il flusso e con sincronizzazione cardiaca, eventualmente abbinati alla funzione cine, sono indubbiamente accurati, raffinati ed eleganti, ma non indispensabili, nella pratica clinica, per lo studio del flusso liquorale; infatti non si è ancora dimostrata una loro significativa maggiore sensibilità rispetto ai dati qualitativi (flusso si/flusso no) ottenibili con normali sequenze FSE e TSE T2 w.

Presso il Servizio di Neuroradiologia dell'Ospedale Bellaria è stato implementato ed avviato un sistema RIS/PACS per la archiviazione e gestione dei dati anagrafici dei pazienti, dei dati alfanumerici associati agli esami e delle immagini. Nel progetto, che si è concretizzato in un Capitolato di gara, è stata formulata la precisa scelta di rinunciare alla documentazione iconografica su pellicola, resa possibile dall'archiviazione delle immagini su CD-R, supporto che preserva la validità legale del documento archiviato. La documentazione iconografica dell'esame viene stampata su carta e consegnata al paziente od ai reparti. Il Capitolato di gara è stato formulato in Service, in considerazione anche della rapida obsolescenza tecnologica delle apparecchiature oggetto del Capitolato. Il cuore del Sistema è rappresentato dalla rete Ethernet (100 Mb/s) cui sono collegati gli apparecchi diagnostici, le Workstations di refertazione e consultazione del sistema PACS, le Workstations del sistema RIS, i film digitizer dedicati alla digitalizzazione dell'archivio storico e dei precedenti dei pazienti, i Server RIS e PACS, il sistema multimediale, le stampanti su carta e pellicola. L'adattamento del personale all'utilizzazione delle nuove tecnologie è stato rapido, verosimilmente anche in conseguenza della relativa facilità di utilizzazione dei programmi descritti (maturità della tecnologia). Nella nostra breve esperienza l'adozione di questo Sistema ha consentito una notevole semplificazione gestionale del Servizio che si è tradotta in un miglioramento della qualità dell'assistenza al paziente, grazie alla: disponibilità presocchè immediata dei precedenti esami del paziente, possibilità di consultazione con altri colleghi disponibilità in tempo reale delle immagini e dei referti nei reparti, essenziale per pazienti critici; drastica riduzione dei tempi di attesa del referto (da una settimana alla consegna immediata) riduzione dei tempi di attesa dei pazienti allo sportello prenotazioni, grazie all'integrazione con il CUP e alla disponibilità dei dati angrafici dei residenti a Bologna.

Vengono riportati i risultati di uno studio su un campione costituito da 132 tumori intracerebrali primitivi operati dal 1 gennaio 1996 al 31 dicembre 1996 presso la Divisione di Neurochirurgia dell'Ospedale Bellaria di Bologna. I tumori erano per la maggior parte gliomi ad alto grado di malignità, poi gliomi a basso grado, gangliocitomi, ependimomi, medulloblastomi. In tutti i casi è stato eseguito un esame neuroradiologico postoperatorio precoce TC o RM prima e dopo somministrazione di mdc. In accordo con i dati riportati in letteratura il controllo postoperatorio è stato effettuato entro il terzo o quarto giorno dall'intervento, affinchè le modificazioni parenchimali conseguenti all'atto chirurgico non rendessero difficoltosa o impossibile la rilevazione della presenza o assenza di residuo neoplastico. È stato scelto di fare lo studio TC nei tumori maligni e lo studio RM nei gliomi a basso grado di malignità o tumori della fossa cranica posteriore. Nei 98 casi in cui la rimozione chirurgica era stata parziale o subtotale anche gli esami neuroradiologici mostravano la presenza di residuo neoplastico. Dei 34 casi in cui il giudizio neurochirurgico era stato di asportazione totale della neoplasia, in 14 era possibile stabilire la presenza di residuo tumorale certo, in 4 dubbio, in 9 non-residuo e in 7, per la presenza di ematoma nel cratere, non era possibile fare una valutazione certa. La necessità di documentare la presenza o meno di residuo neoplastico dopo l'intervento chirurgico nasce da esigenze prognostiche e di pianificazione terapeutica. È stato documentato che la prognosi peggiora drammaticamente in presenza di residuo. Infatti il 75% dei pazienti con glioma maligno, se ha residuo nel controllo postoperatorio, presenta la ripresa della malattia entro 6 mesi, cosa che si verifica solo nel 36% dei pazienti senza residuo. Nella pianificazione della terapia postchirurgica: radioterapia o chemioterapia, la presenza o meno di residuo neoplastico è di fondamentale importanza. Nei tumori maligni in presenza di residuo si può ipotizzare, dopo la radioterapia convenzionale, l'esecuzione di “Boost” focalizzato con radiochirurgia o brachiterapia. Inoltre attualmente si tende ad effettuare chemioterapia solo in caso di presenza di residuo tumorale postoperatorio. Nei tumori a basso grado di malignità la radicalità della chirurgia riveste ancora maggiore importanza. Infatti nei pazienti giovani, al di sotto dei 30 anni di età, se il tumore è stato asportato completamente la radioterapia può essere rimandata fino al momento dell'eventuale ripresa di malattia.

OBJECTIVE AND IMPORTANCE: Ruptured Rathke's cleft cyst is a rare cause of giant cell granulomatous hypophysitis. Chronic inflammatory reaction is caused by extravased cyst content into the adjacent gland. We provide a demonstration that mucins produced by cells lining the cyst wall caused the granulomatous giant cell reaction. CLINICAL PRESENTATION: A 37-year-old nonpregnant woman presented with a 3-year-history of headache and amenorrhea. She had experienced normal sexual maturation, and her medical history was unremarkable. Radiologically, the lesion appeared as an intrasellar mass with a cystic component indistinguishable from a pituitary adenoma with cystic degeneration. TECHNIQUE: The patient underwent a transsphenoidal approach. Because no demarcation between normal and affected tissue was evident at surgery, the lesion and residual pituitary were radically removed. Tissue was studied using routine hematoxylin and eosin and histochemical stainings for mucins and immunocytochemical techniques. CONCLUSION: This study demonstrates that mucins that had spilled out from the cyst caused the granulomatous reaction. Using computed tomography, magnetic resonance imaging, and gross inspection, distinction between granulomatous hypophysitis and pituitary adenoma was virtually impossible. Nevertheless, a granulomatous reaction of the pituitary gland should be suspected in a case of a sellar mass having a cystic area. In such cases, intraoperatory diagnosis on frozen sections is mandatory because adoption of a conservative treatment allows preservation of the gland.

The intradural extramedullary space is an extremely unusual site for the onset of Ewing's sarcoma. We describe a case of recurrence of intradural extramedullary Ewing's sarcoma and review the literature available on this topic.

Patient with surgically treated right temporo-occipito-parietal glioblastoma multiforme Postoperative follow-up performed early (24 hours and 2 weeks) with MR morphologic sequences

Intracranial hemangiopericytomas (HPCs) are rare tumors and their radiological appearance resembles that of meningiomas, especially meningothelial meningiomas. To increase the knowledge on the biochemical composition of this type of tumor for better diagnosis and prognosis, we performed a molecular study using ex vivo high resolution magic angle spinning (HR-MAS) magnetic resonance spectroscopy (MRS) perfomed on HPC and peritumoral edematous tissues. Moreover, to help in the discrimination between HPC and meningothelial meningioma we compared the ex vivo HR-MAS spectra of samples from one patient with HPC and 5 patients affected by meningothelial meningioma. Magnetic resonance imaging (MRI), in vivo localized single voxel 1H-MRS was also performed on the same patients prior to surgery and the in vivo and ex vivo MRS spectra were compared. We observed the presence of OH-butyrate, together with glucose in HPC and a low amount of N-acetylaspartate in the edema, that may reflect neuronal alteration responsible for associated epilepsy. Many differences between HPC and meningothelial meningioma were identified. The relative ratios of myo-inositol, glucose and gluthatione with respect to glutamate are higher in HPC compared to meningioma; whereas the relative ratios of creatine, glutamine, alanine, glycine and choline-containing compounds with respect to glutamate are lower in HPC compared to meningioma. These data will be useful to improve the interpretation of in vivo MRS spectra resulting in a more accurate diagnosis of these rare tumors.

BACKGROUND AND PURPOSE: A growing body of evidence suggests the involvement of the brain in FM. The purpose of this proton MRS study was to test the hypothesis that there are metabolic alterations in some brain regions processing pain (VLPFC and thalamus) in patients with FM compared with HC. MATERIALS AND METHODS: Twelve patients with FM (30–54 years of age; mean age, 43.2 years), and 12 HC, matched for age and sex, underwent 1 session of single-voxel MRS performed on a 3T MR imaging scanner. MRS spectra were acquired with a PRESS for localization. The raw data from each spectrum was evaluated with an LCModel. T tests were used to evaluate differences of brain metabolites between groups. The Pearson correlation tested the relationship of metabolite ratios and clinical symptoms. RESULTS: Glx/Cr and Glu/Cr ratios within the VLPFC of both sides were significantly higher in patients than in HC (P < .01). No significant differences of metabolites between groups were found in the thalami. Positive correlations were found between Glu/Cr in the left thalamus and the VAS for pain (r = 0.730, P = .007) and between mIns/Cr in the right VLPFC and the VAS for pain (r = 0.607, P = .037) and the FIQ (r = 0.719, P = .008). CONCLUSIONS: The presence of elevated Glu/Cr levels in VLPFC strengthens the opinion that a complex neurophysiologic imbalance of different brain areas involved in pain processing underlies FM. These data may be useful in the diagnosis and development of more effective pharmacologic treatments.

O(6)-methylguanine DNA-methyltransferase (MGMT) promoter methylation status is a prognostic factor in newly diagnosed glioblastoma patients. However, it is not yet clear whether, and if so how, MGMT methylation status may change. Moreover, it is unknown whether the prognostic role of this epigenetic feature is retained during the disease course. A retrospective analysis was made using a database of 614 glioblastoma patients treated prospectively from January 2000 to August 2008. We evaluated only patients who met the following inclusion criteria: age > or = 18 years; performance status 0-2; histological diagnosis of glioblastoma at both first and second surgery for recurrence; postoperative treatment consisting of: (i) radiotherapy (RT) followed by adjuvant temozolomide (TMZ) until 2005 and (ii) TMZ concurrent with and adjuvant to RT after 2005; a time interval > or = 3 months between first and second surgery. MGMT status was evaluated at first and second surgery in all 44 patients (M:F 32:12, median age: 49 years, range: 27-67 years). In 38 patients (86.4%), MGMT promoter status was assessable at both first and second surgery. MGMT methylation status, changed in 14 patients (37%) of second surgery samples and more frequently in methylated than in unmethylated patients (61.5% vs 24%, P = .03). The median survival was significantly influenced only by MGMT methylation status determined at first surgery (P = .04). Significant changes in MGMT methylation status during the course of GBM occur more frequently in MGMT methylated than unmethylated cases. MGMT methylation status determined at first surgery appears to be of prognostic value; however, it is not predictive of outcome following second surgery.

BACKGROUND: A recent randomized study conducted on newly diagnosed glioblastoma (GBM) patients demonstrated that concomitant and adjuvant temozolomide added to standard radiotherapy had a survival advantage compared with radiotherapy alone. The overall survival benefit of this aggressive treatment, however, was attenuated in older or poor performance status patients. The aim of the present study was to verify the activity and the toxicity of temozolomide administration concurrent and adjuvant to radiotherapy as first-line treatment for elderly GBM patients, and to explore correlations between clinical outcome and O6 methylguanine-DNA methyltransferase (MGMT) promoter methylation status. METHODS: Newly diagnosed GBM patients ≥65 years were considered eligible. Treatment comprised radiotherapy (60 Gy in 30 fractions over 6 weeks) plus continuous daily temozolomide (75 mg/m2/day), followed by 12 maintenance temozolomide cycles (150 mg/m2 once a day for 5 consecutive days every 28 days) if MRI showed no enhancement suggesting a tumor; otherwise, chemotherapy was delivered until complete response or unequivocal progression. RESULTS: A total of 58 patients (34 males; median age, 68 years; range, 65-82 years) were enrolled. Sixteen patients (43%) presented MGMT promoter methylated and 21 unmethylated (57%) status. The median progression-free survival and median survival time (MST) were 9.5 months (95% confidence interval [CI], 8.6-10.5) and 13.7 months (95% CI, 10-17.3 months), respectively. Mental status deterioration grade 3-4 was detected in 25% of patients. Leukoencephalopathy was diagnosed in 10% of patients. CONCLUSIONS: The overall and progression-free survival of patients given concomitant and adjuvant temozolomide are greater than in those given radiotherapy alone; however, this regimen incurs a greater deterioration in mental status. Further randomized trials should, therefore, be conducted to investigate the efficacy and against the toxicity of this regimen as first-line therapy in patients with GBM. Cancer 2009. © 2009 American Cancer Society.

Primary cerebral lymphoma has varied clinical and imaging presentations making the neuroradiologic diagnosis of primary cerebral lymphoma a challenge. We discuss here three cases of cerebral lymphoma, one primary and two secondary. Our aim is to highlight the importance of diffusion, perfusion and spectroscopy in addition to conventional morphological MRI, and the role of stereotactic biopsy in reaching a correct diagnosis.

During recent years much effort has been put into detecting and classifying disease states, and MR imaging has been a very important tool in this respect. Up to now, increasing the gradient strength has been the only strategy for meeting the increasing demands of advanced diagnostic imaging applications. This strategy is limited by physical, economic, andmedical considerations: increasing gradient strength is technically difficult, and is associated with significant hardware costs and with the risk of inducing unwanted side effects such as peripheral neurostimulation. The main advantage of high-field MR is the improved signal-to-noise ratio, which scales approximately linearly with field strength from 1.5 T to 3 T. This signal can be used to generatemore accurate spatial representation or to speed up imaging times, depending on the specific application. Higher field strengths change tissue contrast parameters. T1 relaxation time is increased by approximately 30%, whereas T2 and T2* relaxation times are decreased by about 15% [37]. Increasing the field strength from 1.5 T to 3 T also doubles chemical shift and susceptibility. MR spectroscopy benefits considerably from the improved spectral resolution possible with high-field MR, and images acquired on 3 T MR demonstrate enhanced sensitivity to the blood oxygen level-dependent (BOLD) effect [77]. On the other hand, tissue heating induced by radiofrequency power is a disadvantage with the use of 3 TMR. In fact, specific RF absorption rate approximately quadruples when field strength increases from 1.5 T to 3 T. The most recent attempt to circumvent these limitations is parallel imaging MRI.

We present the MRI findings of delayed brain damage in a patient who underwent radiotherapy after resection of an oligo-astrocytoma. The lesions appeared years later within brain tissue that was included in radiation fields. High-field 3 Tesla MR investigation gave us the possibility to appreciate the different aspects of the vasculopathy induced by irradiation. A literature review allowed us to hypothesize the correlations between imaging and pathological findings.

Unfortunately, the affiliation of the author name, Antonella Bacci, was incorrectly listed as Antonella Bacci(1) instead of Antonella Bacci(3), and the affiliations were incorrectly listed as (1) Department of Neurosurgery, IRCCS Neurological Research Hospital; Bologna, Italy - (2) Section of Pathology "M. Malpighi", Bellaria Hospital, Azienda USL of Bologna, Bologna, Italy instead of (1) Department of Neurosurgery, (3) Department of Neuroradiology, IRCCS Neurological Research Hospital; Bologna, Italy. (2) Section of Pathology "M. Malpighi", Bellaria Hospital, Azienda USL of Bologna, Bologna, Italy in the original publication of this paper.

2022 Background: The standard treatment in children with average-risk medulloblastoma (MB) is chemotherapy after reduced-dose radiotherapy (23.4 Gy of craniospinal irradiation and a posterior fossa...

2022 Background: In the last decade, progression-free survival (PFS) at 6 months (PFS-6) has been considered the best endpoint in phase II trials on recurrent glioblastoma (GBM). However, since a n...

2052 Background: MGMT methylation status has been found to be an important prognostic factor in glioblastoma patients (pts). However, further data on the epigenetic feature are needed before its role in rare diseases such as anaplastic astrocytomas (AA) can be established. Methods: A retrospective analysis was made on a database of 139 AA pts followed prospectively from January 1995 and August 2008. We evaluated only pts who met the following inclusion criteria: age >18 years; PS 0–2; histological diagnosis of AA; postoperative radiotherapy (RT) and chemotherapy (CT). MGMT status was determined with methylation specific PCR. The study aim was to evaluate the role of MGMT methylation status in AA. The log-rank test was employed to evaluate the significance of the prognostic variables. Results: 80 pts (m/f: 46/34, median age: 41 years, range: 18–71 years) were enrolled. MGMT was assessable in 71 of 80 pts (88.8%), being methylated in 30 (42.9%), and unmethylated in 41 (57.7%) pts. Median PFS was 48.6 months (95% CI: 33.7 - 63.5), being 96 months (95% CI: 29–163) and 38 months (95%CI: 18.9–57.2) in MGMT methylated and unmethylated pts, respectively (p = 0.09). At univariate analysis, complete resection (p = 0.02), age (p = 0.002), and KPS (p = 0.003) were significantly correlated with PFS. At multivariate analysis only age remains correlated with PFS (p = 0.01). Median survival (OS) was 93.7 months (95% CI: 63.5–123.8), being not reached and 77 months (95% CI: 20–134.2), in MGMT methylated and unmethylated pts, respectively (p = 0.03). MGMT methylation (p = 0.03), age (p = 0.0003), and KPS (p = 0.03) were significantly correlated with OS at univariate analysis. At multivariate analysis, age (p = 0.0002) and MGMT methylation (p = 0.01) were correlated with a better OS. Conclusions: MGMT methylation status is an independent prognostic factor together with age in AA. This datum should provide the background to improve the therapeutic index with temozolomide concurrent with and adjuvant to RT in AA. No significant financial relationships to disclose.