Adjuvant chemotherapy in adult medulloblastoma: is it an option for average-risk patients?

The standard treatment in children with average-risk medulloblastoma (MB) is reduced-dose radiotherapy (RT) followed by chemotherapy. However, in adults, there is no agreement on the use of adjuvant chemotherapy. We performed a retrospective analysis of adult MB patients with average-risk disease, defined as no postsurgical residual (or ≤1.5 cm(2)) and no metastatic disease (M0). Main inclusion criteria were: age >16 years, post-surgical treatment with craniospinal irradiation with or without adjuvant chemotherapy (cisplatin and etoposide ± cyclophosphamide). From 1988 to 2012 were accrued 43 average-risk MB patients treated with surgery and adjuvant RT. Fifteen (34.9 %) patients received also chemotherapy: 7 before RT, 5 after RT, and 3 before and after RT. Reasons to administer chemotherapy were presence of residual disease (even if ≤1.5 cm) and delay in RT. After a median follow up time of 10 years (range: 8-13), median survival was 18 years (95 % CI 9-28) in patients who receive RT alone, and was not reached in patients treated with RT plus chemotherapy. The survival rates at 5, 10 and 15 years were 100 %, 78.6 % (95 % CI 60.0-97.2 %) and 60.2 % (95 % CI 36.9-83.5 %), in patients treated with RT alone, and 100, 100 and 100 %, in patients treated with RT plus chemotherapy (p = 0.079). Our findings suggest a role for adjuvant chemotherapy in the treatment of average-risk MB adult patients. Further improvements might drive to add chemotherapy in average-risk setting with less favourable biological signatures (i.e., non-WNT group).

Slowly progressive aphemia: a neuropsychological, conventional, and functional MRI study.

Slowly progressive aphemia (SPA) is a rare focal degenerative disorder characterized by severe dysarthria, frequent orofacial apraxia, dysprosody, phonetic and phonemic errors without global cognitive deterioration for many years. This condition is caused by a degeneration of anterior frontal lobe regions, mainly of the left frontal operculum. We report a case of SPA with a course of 8 years, evaluated by repeated neuropsychological, conventional, and functional MRI examinations. In our case, neuropsychological examinations showed a progressive impairment of speech articulation including dysprosody, phonetic and phonemic errors, and slight writing errors. No global cognitive deterioration was detected and the patient is still completely autonomous. Morphological and functional investigations showed, respectively, a progressive atrophy and progressive impairment of the left frontal region, confirming the role of the opercular region in determining this rare syndrome. During verbal task generation as the cortical activation of this region gradually decreased, the language articulation worsened.

Application of intravoxel incoherent motion (IVIM) magnetic resonance imaging in the evaluation of primitive brain tumours.

Intravoxel incoherent motion is a potential non-invasive diagnostic tool in brain tumours, without any clear guidelines for its evaluation yet. In our study, we compare intravoxel incoherent motion with dynamic susceptibility contrast magnetic resonance imaging in the quantification of tumour tissue blood perfusion in 28 patients affected by brain tumours, highlighting the issues encountered during the acquisition set-up and post-processing steps. Intravoxel incoherent motion is a new imaging tool and an alternative technique to dynamic susceptibility contrast-magnetic resonance imaging which is of considerable interest at present. This is partly because it does not require the use of a contrast agent and relies on the intrinsic properties of motion in the capillaries of the spins. Compared to dynamic susceptibility contrast-magnetic resonance imaging, the intravoxel incoherent motion technique is also characterised by better resolution because the gadolinium-based contrast agent bolus used in the standard technique results in a variation by more than 50% of the signal coming from the brain. Finally, intravoxel incoherent motion is more sensitive to the incoherent motion that originates from small capillary vessels, while the dynamic susceptibility contrast signal is also contaminated by the input from larger arteries and veins, which may result in an overestimation of the blood volume. Although there are limitations due to the heterogeneity of the sample considered in our study, intravoxel incoherent motion has been shown to be an accurate noninvasive radiological biomarker, useful to distinguish between low and high grade glial tumours.

Metabolic findings on 3T 1H-MR spectroscopy in peritumoral brain edema.

BACKGROUND AND PURPOSE: Little is known about the metabolic properties of brain edema associated with tumors. This work was conducted on the basis of the assumption that, in the presence of intra-axial and extra-axial brain tumors, the white matter involved by the edema is a site of metabolic change that involves the structure of the myelin sheath. MATERIALS AND METHODS: Thirteen patients comprised our cohort affected by intra-axial and extra-axial cerebral tumors with a peritumoral T2-weighted MR signal hyperintensity as a result of edema, where MR spectroscopy showed no increase in choline-containing compounds. Measurements on proton MR spectroscopy (1H-MR spectroscopy) were performed with a 3T whole-body scanner with use of a point-resolved spectroscopy sequence for localization (TR, 2000 ms; TE, 35 ms), and the metabolites were quantified with the SAGE method. Peak intensities of the main metabolites were expressed as ratios of one another and were compared with values obtained in the white matter of the left frontal region in a control group of 16 healthy volunteers. RESULTS: Choline-to-creatine (Cho/Cr) and myo-inositol-to-creatine (mIns/Cr) signal intensity ratios were normal in all patients. N-acetylaspartate-to-creatine (NAA/Cr) and N-acetylaspartate-to-choline (NAA/Cho) ratios decreased in 4 patients. Glutamate plus glutamine-to-creatine (Glx/Cr) was increased in 10 patients. A resonance peak at 3.44 ppm, strongly suggesting the presence of glucose, was detected in all but 1 patient. Lactate was detected in 12 patients and lipids in 5. Moreover, the resonances that pertained to the aliphatic amino acids valine, leucine, and isoleucine were present in 12 patients. CONCLUSIONS: Our findings on MR spectroscopy confirmed the hypothesis that in the edema surrounding brain tumors, an energy-linked metabolic alteration was associated with injury to the myelin sheath.

Neuroradiology of spine degenerative diseases.

Degenerative disease of the spine is one of the most common clinical entities and affects the intervertebral discs, including opposing vertebral endplates, the intervertebral posterior joints and the ligaments. The most severe primary spinal degenerative changes are found in the lower cervical and lumbar spine regions. The spine contains three different types of joints, each of which presents its own pattern of degenerative disease: (i) cartilaginous joints, represented by the intervertebral disc or, more specifically, the functional unit defined as the 'vertebro-disc connection'; (ii) synovial joints, represented by the posterior intervertebral joints, sacro-iliac and costovertebral joints; (iii) fibrous joints, mainly found in the principal ligaments such as the posterior longitudinal ligament and the yellow ligaments. With regard to radicular pain, root compression alone does not fully account for root pain following disc-root conflict, but it is, nevertheless, considered to be the main cause of pain. We will try to explain that the origin of pain is multi-factorial and that inflammation probably predominates over merely mechanical mechanisms. To conclude, we will consider whether vertebral arthrosis can be construed as the body's decision to favour the spine's static function over its dynamic role when joint 'hypermobility' linked to chronic load in old age could cause severe structural damage to the bony vertebral structures. This hypothesis should also embrace a further concept: ageing of the spine is not merelychronological. Themostaccurate interpretation tha tcan account for similar degenerative phenomena encountered in the young is that of abnormal static and dynamic loading stress.

[An experimental investigation of the use of a fluorocarbon (FC 43) as blood substitute]. / Ricerca sperimentale sull'impiego di un fluorocarbonato (FC 43) come sostituto ematico.

A fluorocarbonate emulsion was infused into 30 rabbits after the removal of varying amounts of blood. Parameters relating to the transport of respiratory gases and the fundamental features of the macrocirculation were monitored. The animals were sacrificed after 6 or 24 hr and the histological changes in the main parenchymas were assessed. The material injected displayed low toxicity, a good ability to act as a vehicle for oxygen and carbon dioxide, and no tendency to alter the macrocirculation. Numerous problems remain, however, with regard to the stability of fluorocarbonates over the course of time and the effect of their uptake by tissues.

Cardiovascular and biochemical assessment in migraine patients submitted to tilt test.

Ten migraine patients underwent a tilt test both during migraine attack and headache-free interval, and the following parameters were assessed: plasma levels of norepinephrine (NE), and serum dopamine beta hydroxylase (D beta H), systolic and diastolic blood pressure and heart rate (SBP, DBP, HR). SBP during the tilt test showed a fall greater than 30 mmHg in 2 cases in the headache-free interval and in 4 cases during migraine attack. In migraine patients in headache-free interval, tilt test increased NE and D beta H as it did in the control group, while in migraine attack tilt test increased NE and D beta H less than in the control group. This impairment of the sympathetic nervous system during the migraine attack is discussed.

[Oxygenating intra-alveolar lavage (OAL) with the use of some new fluorinated compounds]. / Il lavaggio endoalveolare ossigenante (L.A.O.) mediante l'uso di taluni nuovi composti fluorurati.

Certain fluorinated carbonate compounds can carry O2 and CO2 in a physiological manner. This faculty was exploited in the elaboration of an experimental intra-alveolar oxygenating washing protocol employing such compounds as intrapulmonary oxygenating liquids conveyed by transtracheal flooding of the alveoli in 20 rabbits. AP, PaP, CVP and EP were monitored in accordance with a 35' protocol, during which the positive oxygenation and negative emptying phases of the washing process were repeated at an average 2 cycles/min. A respiratory exchange capable of keeping all the animals alive until the recommencement of spontaneous ventilation was noted, along with only slight changes in lung structure. Once an in-depth study is made of certain fundamental phenomena related to structure and lung function, it is felt that this washing method can be used clinically for the treatment of hypoxaemic situations in which normal alveocapillary exchange is impeded by extraneous material, as in desquamative interstitial pneumonia, pulmonary alveolar proteinosis, etc.

FMRI activation with an "affective speech" paradigm in vegetative and minimally conscious States: applicability and prognostic value.

Vegetative state (VS) and minimally conscious state (MCS) are considered different clinical entities but their differential diagnosis remains challenging. Some VS patients can show an MCS-like activation in functional magnetic resonance imaging (fMRI) studies that seems to predict recovery from VS. We studied fMRI activation with an affective speech paradigm in a cohort of non-communicative brain-injured individuals consecutively admitted to a post-acute neurorehabilitation facility in five years. Among 93 eligible subjects, 65 met the clinical criteria for VS and 28 for MCS. Because of exclusion criteria, activation studies were performed in only 30 cases out of 93 and analysed in only 24 (about » of the eligible cases): 19 VS and five MCS patients. The passive acoustic stimulus consisted in a familiar voice narrating a significant episode in the patient's life, administered by nonmagnetic earphones. All the MCS patients showed an activation spread to secondary associative cortices but also 52.7% of the VS patients displayed an "atypical" large-scale activation pattern. Regarding the clinical outcome, 80% of the patients with large-scale network activation (LSNA) had some recovery of consciousness. Our results confirm that the VS patients with LSNA at fMRI study have potential for further recovery of consciousness, whereas no patient without activation or only typical activation improved. fMRI study with an affective speech paradigm, when applicable, seems to have a valuable prognostic value in VS patients, even if there are major limitations in terms of applicability.

Complications in the treatment of intracranial aneurysms with silk stents: an analysis of 30 consecutive patients.

Flow-diverting stents (Silk and PED) have radically changed the approach to intracranial aneurysm treatment from the use of endosaccular materials to use of an extraaneurysmal endoluminal device. However, much debate surrounds the most appropriate indications for the use of FD stents and the problems raised by several possible complications.We analysed our technical difficulties and the early (less than ten days after treatment) and late complications encountered in 30 aneurysms treated comprising 13 giant lesions, 12 large, five with maximum diameters <10 mm and one blister-like aneurysm. In our experience the primary indications for the use of FD stents can be the symptomatic intracavernous giant aneurysms. Although the extracavernous carotid siphon aneurysms have major risk of bleeding, FD stents are indicated clearly explaining the risks to the patient in case of severe mass effect. There is a very complex assessment for aneurysms of the vertebrobasilar circulation.

Treatment of intracranial aneurysms using flow-diverting silk stents (BALT): a single centre experience.

The Silk stent (Balt, Montmorency, France) is a retractable device designed to achieve curative reconstruction of the parent artery associated with an intracranial aneurysm. We present our initial experience with the Silk flow-diverting stent in the management and follow-up of 25 patients presenting with intracranial aneurysms.Twenty-five patients (age range, 34-81 years; 24 female) were treated with the Silk flow-diverting device. Aneurysms ranged in size from small (5), large (10) and giant (10) and included wide-necked aneurysms, multiple, nonsaccular, and recurrent intracranial aneurysms. Nine aneurysms were treated for headache, 14 for mass effect. None presented with haemorrhage. All patients were pretreated with dual antiplatelet medications for at least 72 hours before surgery and continued taking both agents for at least three months after treatment. A total of 25 Silk stents were used. Control MR angiography and/or CT angiography was typically performed prior to discharge and at one, three, six and 12 months post treatment. A follow-up digital subtraction angiogram was performed between six and 19 months post treatment.Complete angiographic occlusion or subtotal occlusion was achieved in 15 patients in a time frame from three days to 12 months. Three deaths and one major complication were encountered during the study period. Two patients, all with cavernous giant aneurysms, experienced transient exacerbations of preexisting cranial neuropathies and headache after the Silk treatment. Both were treated with corticosteroids, and symptoms resolved completely within a month.In our experience the Silk stent has proven to be a valuable tool in the endovascular treatment of intracranial giant partially thrombosed aneurysms and aneurysms of the internal carotid artery cavernous segment presenting with mass effect. The time of complete occlusion of the aneurysms and the risk of the bleeding is currently not predictable.

Quantitative cervical spinal cord 3T proton MR spectroscopy in multiple sclerosis.

BACKGROUND AND PURPOSE: Brain proton MR spectroscopy ((1)H-MR spectroscopy) is a useful technique for evaluating neuronal/axonal damage and demyelization in multiple sclerosis (MS). Because MS disability is frequently related to spinal cord lesions, potential markers for MS stage differentiation and severity would require in vivo quantification of spinal integrity. However, few spectroscopy studies have investigated cervical disease due to technical difficulties. The present study used 3T (1)H-MR spectroscopy to measure the main metabolites in cervical spinal cord plaques of a group in patients with relapsing-remitting MS (RRMS) and compared them with metabolite measurements in healthy volunteers. MATERIALS AND METHODS: A (1)H-MR point-resolved spectroscopy sequence volume of interest was prescribed along the main axis of the cord between C2 and C3 levels on a plaque in a group of 15 patients with RRMS for a total acquisition time of approximately 14 minutes. MR spectroscopy data were analyzed by the user-independent fitting routine LCModel, and relative metabolite concentrations were expressed by the absolute concentration ratios. A Student t test was used to evaluate the difference compared with the healthy metabolite content previously published. RESULTS: We found a significant decrease of total N-acetylaspartate/choline and an increase in choline/creatine and myo-inositol/creatine content on MS plaques in comparison with healthy cervical spine tissue. CONCLUSIONS: In vivo (1)H-MR spectroscopy, if confirmed by other similar studies, should be as reliable for clinical studies as it is in brain imaging. Moreover, (1)H-MR spectroscopy allows examination of spinal cord integrity at a biochemical level and may be sensitive to subtle changes occurring during the course of MS disease.

Potential of high field functional MRI in the neuroradiological diagnosis of brain tumours.

Functional 3 tesla magnetic resonance imaging (MRI) techniques such as diffusion and perfusion imaging and MR spectroscopy (MRS) allow a more accurate diagnosis of central nervous system tumours. This retrospective study analysed the MRI scans of 121 consecutive patients with a diagnosis of glial brain tumours who underwent surgery and/or biopsy and whose histological reports were available. Our aim was to establish if and how functional MRI techniques had enhanced the diagnostic accuracy with respect to morphological examination. To quantify the diagnostic contribution of these techniques and their predictive value, a questionnaire was compiled by an observer blinded to the neuroradiological diagnosis and to the histological results after surgery/biopsy. Patients were divided into two groups based on the time of 3T MRI examination performed: before or after surgery/biopsy. In the group of non-operated patients low grade gliomas could be distinguished from high grade malignant tumours, whereas in the group of operated patients signs of tumour persistence or recurrence could be distinguished from the effects of previous treatments. Functional MRI techniques improved the accuracy of diagnosis with respect to morphological examination alone in both groups of patients: areas of increased cellularity, neoangiogenesis or metabolic changes were identified confirming diagnosis, whereas methodological errors were disclosed in cases of incorrect diagnosis.

Amyloidoma Involving the Orbit, Meckel's Cave and Infratemporal Fossa: 3T MRI Findings.

Amyloidoma is a rare lesion characterized by tissue deposition of an abnormal fibrillary protein (amyloid). It is the focal and localized counterpart of systemic amyloidosis, where the deposition of amyloid diffusely involves several organs. The few literature reports of intracranial amyloidomas include lesions involving the pituitary gland, orbit, cerebral hemispheres, temporal bone, cerebellopontine angle and jugular foramen. We describe the case of a 27-year-old woman presenting with painless slowly progressive proptosis of the right eye. The patient underwent a contrast-enhanced CT study of the head, followed by 3T MRI which disclosed a homogeneous mass in the right Meckel's cave and cavernous sinus, extending through an enlarged foramen ovale to the infratemporal fossa. The right optic nerve and ocular muscles were enlarged and infiltrated along with the retrobulbar fat by contrast-enhancing tissue. Thin contrast-enhanced MRI scans through the area of interest showed the mass to extend posterior to the gasserian ganglion, involving the cerebellopontine angle cistern, where the intracisternal parts of the III, V, and VI nerves bilaterally appeared enlarged and showed perineural enhancement. The lesion closely mimicked a malignant tumor with perineural tumor infiltration, so we performed fine needle biopsy of the portion of the lesion near the right foramen ovale under fluoroscopic guidance. Histopathology revealed that the lesion was an amyloidoma. Further clinical and blood examinations, serum chemistry, followed by biopsy of the periumbilical fat showed no signs of systemic amyloidosis or an underlying inflammatory or neoplastic disorder. No further treatment was instituted, follow-up MRI six months later showed no enlargement of the mass.

Thyrotropin-secreting pituitary tumours: significance of "atypical adenomas" in a series of 10 patients and association with Hashimoto thyroiditis as a cause of delay in diagnosis.

BACKGROUND: Thyrotropin-secreting adenomas (TSH-As) are rare and, according to the World Health Organization criteria (WHO 2004), a significant proportion of them present features of atypical adenomas at the time of diagnosis. AIMS: To determine the frequency of "atypical adenomas" and the significance of this definition as regards follow-up. To investigate their possible association with Hashimoto thyroiditis, leading to a delay in diagnosis. METHODS: Case notes for patients who underwent trans-sphenoidal surgery between 1992 and 2006 were retrieved. Follow-up ranged from 6 to 180 months. RESULTS: Ten cases of TSH-As out of 908 pituitary adenomas were selected. Before surgery, eight patients had hyperthyroidism, one was euthyroid and another one showed hypothyroidism associated with Hashimoto thyroiditis. All cases were macroadenomas; six of them were invasive. Three cases met the criteria for classification as atypical. In none of the cases, including the three "atypical adenomas", were clinical or radiological signs of recurrence observed. CONCLUSIONS: The three cases with features of atypical adenoma did not recur or metastasise, suggesting that, at least in the present series, a strict relationship between the morphological criteria for diagnosing atypical adenomas and biological behaviour may be sometimes lacking. Furthermore, the casual association of TSH-As with Hashimoto thyroiditis may led to an adjunctive delay in diagnosis, because of low thyroid hormone levels.

Importance of functional MRI and the role of stereotactic biopsy in the diagnosis of cerebral lymphoma.

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.

Metabolite Changes in Normal Appearing Cervical Spinal Cord in Two Patients with Multiple Sclerosis. A Proton MR Spectroscopic Analysis.

We describe two cases of multiple sclerosis (MS) analyzed with Proton MR Spectroscopy ((1)H-MRS) with the voxel placed along the main axis of the normal appearing cervical spinal cord over three main space planes, orthogonally set. Relative concentrations expressed by the absolute concentration ratios of total NAA (tNAA), choline (Cho), myo-inositol (mI) and creatine plus phosphocreatine (Cr) were compared with the metabolites of ten healthy volunteers. We found a significant increase in mI/Cr and a small increase in Cho/Cr in the first patient, whereas the second patient had a decrease in NAA/Cr and NAA/Cho ratios. 1H-MRS will disclose biochemical changes in MS, even in normal appearing spinal cord, as already described in normal appearing cerebral tissue: these biochemical changes may provide significant information on disease prognosis.

Evolutive study of relapsing-remitting multiple sclerosis with cervical proton magnetic resonance spectroscopy. A case report.

We used quantitative proton magnetic resonance spectroscopy ((1)H-MRS) to evaluate mean relative concentrations ratios for NAA, Cr, Cho and mI during the study of cervical spinal cord plaques in a relapsing-remitting multiple sclerosis (RRMS). A cervical spine MR exam was repeated five times on the following days for two months starting from the onset of a relapse phase, using a 3T whole-body system, with the voxel placed along the demyelinazation lesion. The quantification results were compared with the healthy metabolites content. Quantitative cervical spectroscopy is a reliable tool and can offer important metabolic information as already used on the brain to evaluate the severity, progression and pathogenesis of multiple sclerosis.

Extracentral nervous system metastases from medulloblastoma. A case report.

Medulloblastoma belongs to the group of highly malignant neuroepithelial tumours and is the commonest tumour in childhood (12-25 %) (1), but is rare in adults (0.4-1%) of all primary brain tumours) (1,2). Medulloblastomas usually arise in the posterior fossa and spread readily throughout the CSF, although 10-30% of patients develop extracentral nervous system metastases (2). We describe a 30-year-old woman presenting bone metastases from medulloblastoma located predominantly in the spine.