M. Leonardi

WEB-DL Endovascular Treatment of Wide-Neck Bifurcation Aneurysms: Short- and Midterm Results in a European Study

Short- and midterm results of endovascular aneurysm treatment with the new WEB-DL device were assessed in 45 patients from 12 European centers. Of these, 42 aneurysms were unruptured and most were located either in the MCA bifurcation or the posterior circulation. Adequate occlusion was observed in 81% and 90% of aneurysms at 6 and 13 months, respectively. Results suggest that WEB endovascular treatment of wide-neck bifurcation aneurysms offers stable occlusion in a class of aneurysms that are historically unstable. BACKGROUND AND PURPOSE: Flow disruption with the WEB-DL device has been used safely for the treatment of wide-neck bifurcation aneurysms, but the stability of aneurysm occlusion after this treatment is unknown. This retrospective multicenter European study analyzed short- and midterm data in patients treated with WEB-DL. MATERIALS AND METHODS: Twelve European neurointerventional centers participated in the study. Clinical data and pre- and postoperative short- and midterm images were collected. An experienced interventional neuroradiologist independently analyzed the images. Aneurysm occlusion was classified into 4 grades: complete occlusion, opacification of the proximal recess of the device, neck remnant, and aneurysm remnant. RESULTS: Forty-five patients (34 women and 11 men) 35–74 years of age (mean, 56.3 ± 9.6 years) with 45 aneurysms treated with the WEB device were included. Aneurysm locations were the middle cerebral artery in 26 patients, the posterior circulation in 13 patients, the anterior communicating artery in 5 patients, and the internal carotid artery terminus in 1 patient. Forty-two aneurysms were unruptured. Good clinical outcome (mRS < 2) was observed in 93.3% of patients at the last follow-up. Adequate occlusion (complete occlusion, opacification of the proximal recess, or neck remnant) was observed in 30/37 patients (81.1%) in short-term follow-up (median, 6 months) and in 26/29 patients (89.7%) in midterm follow-up (median, 13 months). Worsening of the aneurysm occlusion was observed in 2/28 patients (7.1%) at midterm follow-up. CONCLUSIONS: The results suggest that the WEB endovascular treatment of wide-neck bifurcation aneurysms offers stable occlusion in a class of aneurysms that are historically unstable. Additionally, our data show that opacification of the WEB recess can be delineated from true neck or aneurysm remnants.

Epidemiology and genetics of intracranial aneurysms

Intracranial aneurysms are acquired lesions (5-10% of the population), a fraction of which rupture leading to subarachnoid hemorrhage with devastating consequences. Until now, the exact etiology of intracranial aneurysms formation remains unclear. The low incidence of subarachnoid hemorrhage in comparison with the prevalence of unruptured IAs suggests that the vast majority of intracranial aneurysms do not rupture and that identifying those at highest risk is important in defining the optimal management. The most important factors predicting rupture are aneurysm size and site. In addition to ambiental factors (smoking, excessive alcohol consumption and hypertension), epidemiological studies have demonstrated a familiar influence contributing to the pathogenesis of intracranial aneurysms, with increased frequency in first- and second-degree relatives of people with subarachnoid hemorrhage. In comparison to sporadic aneurysms, familial aneurysms tend to be larger, more often located at the middle cerebral artery, and more likely to be multiple. Other than familiar occurrence, there are several heritable conditions associated with intracranial aneurysm formation, including autosomal dominant polycystic kidney disease, neurofibromatosis type I, Marfan syndrome, multiple endocrine neoplasia type I, pseudoxanthoma elasticum, hereditary hemorrhagic telangiectasia, and Ehlers-Danlos syndrome type II and IV. The familial occurrence and the association with heritable conditions indicate that genetic factors may play a role in the development of intracranial aneurysms. Genome-wide linkage studies in families and sib pairs with intracranial aneurysms have identified several loci on chromosomes showing suggestive evidence of linkage, particularly on chromosomes 1p34.3-p36.13, 7q11, 19q13.3, and Xp22. For the loci on 1p34.3-p36.13 and 7q11, a moderate positive association with positional candidate genes has been demonstrated (perlecan gene, elastin gene, collagen type 1 A2 gene). Moreover, 3 of the polymorphisms analyzed in 2 genes (endothelial nitric oxide synthase T786C, interleukin-6 G572C, and interleukin-6 G174C) were found to be significantly associated with ruptured/unruptured aneurysms: the endothelial nitric oxide synthase gene single-nucleotide polymorphisms increased the risk, while IL-6 G174C seemed protective. More recently, two genomic loci (endothelin receptor A and cyclin-dependent kinase inhibitor 2BAS) have been found to be significantly associated with intracranial aneurysms in the Japanese population; endothelin-1 is a potent vasoconstrictor produced by the endothelial cells. Until now, there are no diagnostic tests for specific genetic risk factors to identify patients who are at a high risk of developing intracranial aneurysms. Knowledge of the genetic determinants may be useful in order to allow clues on stopping aneurysm formation and obtain diagnostic tools for identifying individuals at increased risk. Further multicenter studies have to be carried out.

Quantitative proton magnetic resonance spectroscopy of the human cervical spinal cord at 3 tesla

Cervical spinal cord spectroscopy has the potential to add metabolic information to spinal cord MRI and improve the clinical evaluation and research investigation of spinal cord diseases, such as multiple sclerosis (MS) and intraspinal tumors. However, in vivo proton MR spectroscopy (1H‐MRS) of the spinal cord is difficult to perform due to magnetic field inhomogeneities, physiological movements, and the size of the anatomical region of interest (ROI). For these reasons, few spinal cord 1H‐MRS studies have been undertaken and two preliminary studies on a 3T system were only recently presented as abstracts. In this work we demonstrate the feasibility of cervical spinal cord quantitative 1H‐MRS on a clinical 3T system, propose a study protocol, and report quantification results obtained from healthy volunteers. The main metabolite concentration ratios obtained in 10 healthy subjects, as provided by LCModel, were as follows: total N‐acetyl aspartate/creatine (tNAA/Cr) 1.4 ± 0.3, choline/creatine (Cho/Cr) 0.5 ± 0.1, and myoinositol/creatine (mI/Cr) 1.7 ± 0.2. A significant difference was found between spinal cord tNAA, Cr, Cho, and mI concentration ratios and brainstem concentrations previously acquired on the same system. Magn Reson Med 57:160–163, 2007.

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.

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.

Quantitative Cervical Spinal Cord 3T Proton MR Spectroscopy in Multiple Sclerosis

BACKGROUND AND PURPOSE: Brain proton MR spectroscopy (1H-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 1H-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 1H-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 1H-MR spectroscopy, if confirmed by other similar studies, should be as reliable for clinical studies as it is in brain imaging. Moreover, 1H-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.

Glubran 2: A new acrylic glue for neuroradiological endovascular use: Experimental study on animals

A new acrylic glue, Glubran 2, is now available on the European market. It bears the CE mark with several surgical indications and the specific indication for neuroradiological endovascular use. Despite this approval, to our knowledge its use is still limited to surgery and no injections have been made in human patients. This study was designed to evaluate the behavior of Glubran 2 in endovascular injection in a simulation of brain AVM. Six sheep were operated on opening a fistula between the right common carotid artery and the jugular vein. This fistula modifies blood flow in the skull base rete mirabilis, which then functions as an AVM. In two sheep, the rete mirabilis was occluded by injection of 1.5 ml of Histoacryl diluted 1:1 and 1:3 with Lipiodol. In two sheep, the rete was embolized by injection of 1.5 ml of Glubran 2 diluted 1:1 with Lipiodol. The last two sheep were embolized by injection of Glubran 2 diluted 1:3 with Lipiodol. The procedures were documented by DSA angiographic acquisitions and by fluoroscopic VHS. The sheep were killed immediately after the procedures and the rete mirabilis isolated for histologic examination. Embolization was obtained with both kinds of glue. Glubran 2 diffuses in a very similar way to Histoacryl with an apparently more complete diffusion. Reflux in the ascending pharyngeal artery showed that Glubran 2 tended not to produce bubbles but diffused more homogeneously. The subjective conclusion of this work is that Glubran 2 can be used in endovascular embolizations. Before approaching brain AVMs, a further study will investigate embolization of the external carotid territory.

WEB-DL Endovascular Treatment of Wide-Neck Bifurcation Aneurysms: Long-Term Results in a European Series

BACKGROUND AND PURPOSE: Flow disruption with the WEB-DL device has been used safely for the treatment of wide-neck bifurcation aneurysms. The stability of aneurysm occlusion after this treatment was evaluated in the short and midterm, but not in the long term. This retrospective multicenter European study is the continuation of an already published series dealing with short- and midterm anatomic results and analyzes long-term data in patients treated with the WEB-DL. MATERIALS AND METHODS: Twelve European neurointerventional centers initially participated in the study. In addition to data collected for the initial publication, images obtained at long-term follow-up were collected and independently analyzed by the same experienced interventional neuroradiologist. RESULTS: Of the initial 45 patients, 26 (20 women and 6 men; 35–73 years of age; mean, 55.2 ± 10.6 years; median, 55.5 years) with 26 aneurysms treated with the WEB-DL device had long-term follow-up (median, 27.4 months). Three of 26 patients (11.5%) were retreated between short- and midterm follow-up, and none, between mid- and long-term follow-up. Long-term aneurysm occlusion in the 19 patients treated with the WEB only and not retreated during follow-up was complete occlusion in 13/19 patients (68.4%), including aneurysms with opacification of the proximal recess in 9/19 patients (47.4%), neck remnant in 3/19 patients (15.8%), and aneurysm remnant in 3/19 patients (15.8%). In all patients (100.0%), aneurysm occlusion was stable between midterm and long-term follow-up. CONCLUSIONS: The results suggest that WEB treatment of wide-neck bifurcation aneurysms offers long-term stable occlusion.

Brain functional changes in patients with ulcerative colitis: A functional magnetic resonance imaging study on emotional processing

Background: Ulcerative colitis (UC) is associated with psychological stress and poor emotional functioning. The neural emotional processing involves the complex integration of several cortical and subcortical brain structures. The amygdala plays a fundamental role in the neural processing of emotional stimuli and is a core structure of the brain–gut axis (BGA) that represents the anatomo‐functional substrate for the bidirectional influences between emotions and gastrointestinal functions. The aim of this study was to investigate the brain emotional processing in UC patients compared to healthy people. Methods: Ten UC patients in remission and 10 matched healthy controls underwent a functional magnetic resonance imaging (fMRI) scan while performing a task involving emotional visual stimuli. A set of negative, positive, and neutral pictures were used to study brain‐related emotional responses. Results: A significantly reduced blood oxygen level‐dependent (BOLD) signal in UC patients relative to controls was found in the amygdala, thalamic regions, and cerebellar areas (P < 0.05 corrected for multiple comparisons). The group‐related differences were detected in the brain activity in response to positive emotional stimuli. Conclusions: UC is associated with an emotional dysfunction characterized by decreased sensitivity to emotions with a positive content. The previous intestinal inflammatory activity in UC patients might have contributed to determine the functional changes of the amygdala that we found. On the other hand, the dysfunction of the amygdala may influence the course of the disease. (Inflamm Bowel Dis 2010;)

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.