Vincenzo D’Angelo

Multiparametric 3T MR approach to the assessment of cerebral gliomas: tumor extent and malignancy.

IntroductionContrast-enhanced MR imaging is the method of choice for routine assessment of brain tumors, but it has limited sensitivity and specificity. We verified if the addition of metabolic, diffusion and hemodynamic information improved the definition of glioma extent and grade.MethodsThirty-one patients with cerebral gliomas (21 high- and 10 low-grade) underwent conventional MR imaging, proton MR spectroscopic imaging (1H-MRSI), diffusion weighted imaging (DWI) and perfusion weighted imaging (PWI) at 3 Tesla, before undergoing surgery and histological confirmation. Normalized metabolite signals, including choline (Cho), N-acetylaspartate (NAA), creatine and lactate/lipids, were obtained by 1H-MRSI; apparent diffusion coefficient (ADC) by DWI; and relative cerebral blood volume (rCBV) by PWI.ResultsPerienhancing areas with abnormal MR signal showed 3 multiparametric patterns: “tumor”, with abnormal Cho/NAA ratio, lower ADC and higher rCBV; “edema”, with normal Cho/NAA ratio, higher ADC and lower rCBV; and “tumor/edema”, with abnormal Cho/NAA ratio and intermediate ADC and rCBV. Perienhancing areas with normal MR signal showed 2 multiparametric patterns: “infiltrated”, with high Cho and/or abnormal Cho/NAA ratio; and “normal”, with normal spectra. Stepwise discriminant analysis showed that the better classification accuracy of perienhancing areas was achieved when regarding all MR variables, while 1H-MRSI variables and rCBV better differentiated high- from low-grade gliomas.ConclusionMultiparametric MR assessment of gliomas, based on 1H-MRSI, PWI and DWI, discriminates infiltrating tumor from surrounding vasogenic edema or normal tissues, and high- from low-grade gliomas. This approach may provide useful information for guiding stereotactic biopsies, surgical resection and radiation treatment.

Proton MR spectroscopy of cerebral gliomas at 3 T: spatial heterogeneity, and tumour grade and extent

This study aimed to evaluate the usefulness of proton MR spectroscopic imaging (1H-MRSI) at 3 T in differentiating high- from low-grade gliomas, and tumour from necrosis, oedema or normal tissue. Forty-four patients with brain gliomas and four with meningiomas were retrospectively reviewed. The normalised metabolites choline (nCho), N-acetylaspartate (nNAA), creatine (nCr) and lactate/lipids (nLL), and the metabolite ratios Cho/NAA, NAA/Cr and Cho/Cr were calculated. Necrotic-appearing areas showed two spectroscopic patterns: “necrosis” with variable nCho and high nLL, and “cystic necrosis” with variable nLL or nonevident peaks. Peri-enhancing oedematous-appearing areas showed three spectroscopic patterns (“tumour” with abnormal Cho/NAA, “oedema” with normal Cho/NAA and “tumour/oedema” with normal nCho and abnormal Cho/NAA) in gliomas, and one (“oedema”) in meningiomas. Peri-enhancing or peri-tumour normal-appearing areas showed two patterns (“infiltrated” with abnormal nCho and/or Cho/NAA and “normal” with normal spectra) in gliomas and one (“normal”) in meningiomas. Discriminant analysis showed that classification accuracy between high- and low-grade glioma masses was better with normalised metabolites or all parameters together than metabolite ratios and that among peri-enhancing areas was much better with normalised metabolites. The analysis of spatial distribution of normalised metabolites by 3-T 1H-MRSI helps to discriminate among different tissues, offering information not available with conventional MRI.

Congenital Absence of the Internal Carotid Artery

Abstract We report three cases of congenital absence of an internal carotid artery (ICA), diagnosed incidentally by digital subtraction angiography. The analysis of the cases is based on the classification of segmental ICA agenesis proposed by Lasjaunias and Berenstein. Usually the patients with this rare vascular anomaly are asymptomatic; some may have symptoms related to cerebrovascular insufficiency, compression by enlarged intracranial collateral vessels, or complications associated with cerebral aneurysms. Diagnosis of congenital absence of ICA is made by skull base computed tomography (CT) scan, CT and magnetic resonance angiography, and conventional or digital subtraction angiography.

Treatment of Symptomatic Intracranial Arachnoid Cysts by Stereotactic Cyst-Ventricular Shunting

Background: The optimal treatment of symptomatic intracranial arachnoid cysts is controversial and different surgical approaches have been described. The aim of the treatment is to reduce the intracystic pressure. To accomplish this goal, many techniques have been proposed, each with specific limitations or failures. Methods: Nine patients with symptomatic arachnoid cysts were treated by stereotactic cyst-ventricular shunting. One patient with suprasellar arachnoid cyst showed signs related to intracranial pressure, the remaining 8 patients complained of headache and/or drug-resistant epilepsy. All the intracranial cysts were supratentorial. The surgical procedure was performed under general anesthesia in 6 cases and local anesthesia in 3 cases. The CRW Stereotactic System (Radionics) was used. The acquisition of both target points (cyst and ventricle) was always realized by means of CT scan slices. A right precoronal burr hole was made and a silicon catheter was stereotactically inserted into the lateral ventricle. Another burr hole was subsequently performed close to the cyst; a silicon catheter was placed in the middle of the cavity in the shortest intracerebral crossing. Then both catheters were connected to a subcutaneous burr hole Ommaya reservoir. Results: All patients tolerated the procedure well and the preoperative clinical signs progressively disappeared or improved. The CT scan at 1, 3, 6 and over 12 months showed progressive reduction in size of the cysts. No clinical recurrence was found at the follow-up (14–73 months). Conclusions: The successful outcome of the above cases suggests that, in carefully selected symptomatic intracranial arachnoid cysts, stereotactic cyst-ventricular shunting is likely to prove an effective operative method.

Solitary Fibrous Tumor of the Central Nervous System Report of an Additional 5 Cases With Comprehensive Literature Review

Solitary fibrous tumor (SFT) of the central nervous system was first described in 1996. A number of cases have been reported since. The authors present 5 new cases: 4 intracranial and 1 intraspinal. All patients were adults (age range, 47 to 75 years); 4 were male and 1 female; 4 cases were primary tumors; and 1 was a second tumor recurrence. All patients were surgically treated with gross total removal. All cases were histologically examined with immunohistochemical confirmation; 2 tumors exhibited diffuse classic histology, 1 tumor was a cellular variant, 1 tumor was myxoid, and 1 was predominantly classic with focal myxoid features and focally pleomorphic. The postoperative course was uneventful in all. The patient with the cellular variant experienced 2 local recurrences and eventually died of disease 10 years after the initial diagnosis. The patient with the myxoid variant—the tumor studied—which was the second recurrence of a previously misdiagnosed fibrous meningioma surgically treated 15 years earlier, had a recurrence after 2 years for the third time and eventually died of disease. Three patients are alive and well 11.6, 6, and 4 years after surgery. SFT is a rare tumor that needs to be differentiated from some mimickers, mainly fibrous meningioma, hemangiopericytoma, and with regard to the myxoid variant, also adult-onset myxochordoid meningioma and myxoid peripheral nerve sheath tumor. Immunohistochemistry is crucial for the correct diagnosis of SFT. The authors also performed a review of the literature and found a little more than 200 cases on record.

Cervical cyst of the ligamentum flavum and C7-T1 subluxation: case report

A patient with progressive gait disturbance resulting from a cyst of the cervical ligamentum flavum associated with C7-T1 listhesis is reported. Surgical removal of the cyst improved the patient’s myelopathy. Intraspinal degenerative cysts are preferentially located in the lumbar region:unusual is the cervical localization. Differential diagnosis includes ligamentum flavum cyst, synovial and ganglion cysts. Association between degenerative intraspinal cysts and listhesis is discussed. To our knowledge, this is the first case of cyst of the ligamentum flavum associated with cervical subluxation.

Identification of two novel mutations and of a novel critical region in the KRIT1 gene.

Cerebral cavernous malformations (CCMs) represent a common autosomal dominant disorder that predisposes patients to hemorrhagic strokes and focal neurological signs. Mutations in three genes (KRIT1, MGC4607, and PDCD10) have been associated with CCMs. We investigated the role of two new mutations in the KRIT1 gene in two Italian families affected by CCMs. Whole blood DNA was extracted and the mutations were detected after polymerase chain reaction (PCR), denaturing high-performance liquid chromatography screening, and sequencing of the coding regions of the three CCMs-associated genes. Total RNA was extracted, and the KRIT1 cDNA was sequenced and subsequently subjected to real-time quantitative PCR in order to examine the translational outcome of each genomic mutation. A novel splicing acceptor site deletion of the exon 14 in one family and an intronic nucleotide change close to the exon 19 in the other one were identified, both in the KRIT1 gene. These mutations were proven to alter the correct splicing mechanism, resulting, respectively, in a truncated protein of 432 amino acids and in a protein lacking an internal segment. We report two novel cases of splicing affecting genomic variants, suggesting a careful reanalysis of previously identified splice site variations in KRIT1 to look for their possible causative roles of similar missplicing events and their consequent involvement in the pathogenesis of CCMs. Moreover, our genotype–phenotype functional correlation suggests that the C-terminal portion of the KRIT1 protein is likely to contain a short, previously unrecognized segment necessary for its activity.

TRIM8 downregulation in glioma affects cell proliferation and it is associated with patients survival.

BackgroundHuman gliomas are a heterogeneous group of primary malignant brain tumors whose molecular pathogenesis is not yet solved. In this regard, a major research effort has been directed at identifying novel specific glioma-associated genes. Here, we investigated the effect of TRIM8 gene in glioma.MethodsTRIM8 transcriptional level was profiled in our own glioma cases collection by qPCR and confirmed in the independent TCGA glioma cohort. The association between TRIM8 expression and Overall Survival and Progression-free Survival in TCGA cohort was determined by using uni-multivariable Cox regression analysis. The effect of TRIM8 on patient glioma cell proliferation was evaluated by performing MTT and clonogenic assays. The mechanisms causing the reduction of TRIM8 expression were explored by using qPCR and in vitro assays.ResultsWe showed that TRIM8 expression correlates with unfavorable clinical outcome in glioma patients. We found that a restored TRIM8 expression induced a significant reduction of clonogenic potential in U87MG and patient’s glioblastoma cells. Finally we provide experimental evidences showing that miR-17 directly targets the 3′ UTR of TRIM8 and post-transcriptionally represses the expression of TRIM8.ConclusionsOur study provides evidences that TRIM8 may participate in the carcinogenesis and progression of glioma and that the transcriptional repression of TRIM8 might have potential value for predicting poor prognosis in glioma patients.

Large pure intracranial vagal schwannoma

We report a patient with a large, pure intracranial vagal schwannoma, compressing the medulla who presented with essential hypertension. Based on this and on previous cases, we suggest that a differentiation of pure intracranial schwannomas (subtype A1) from intracranial schwannomas with some extension in the jugular foramen (type A) should be used.

Local and Distant Recurrence

46-year-old patient with right frontal-insular glioblastoma multiforme treated with subtotal excision and combined radiation therapy-chemotherapy and subsequent second-level adjuvant chemotherapy 3T multimodal MR follow-up performed with morphologic imaging, diffusion, perfusion and spectroscopy preoperatively and at 6, 9 and 12 months after surgery and combined radiation therapy-chemotherapy