Blood-brain barrier damage associates with glia-related cytokines in the cerebrospinal fluid of patients with Multiple Sclerosis.

BACKGROUND: The presence of Blood-Brain Barrier (BBB) dysfunction is defined by albumin quotient (QALB) and characterize a group of Multiple Sclerosis (MS) patients at clinical onset. We evaluated the concentration in cerebrospinal fluid (CSF) of 87 cytokines, to better characterize the CSF inflammatory pattern in presence of BBB damage. MATERIALS AND METHOD: In an exploratory cohort, CSF cytokines were evaluated by means of Multiplex technology (Bio-Plex Pro-Human Cytokine, GF and Diabetes 27-Plex Panel, Bio-Plex Pro-Human Chemokines 40-Plex Panel, Bio-Plex Pro-Human Inflammation Assays 37-Plex Panel) in a cohort of Other Not Inflammatory Neurological Disorders (ONIND) and in cohort of patients with MS, stratified according to BBB damage into QALB+ and QALB- MS patients. In the validation cohort, we evaluated the relevant molecules in a cohort of MS patients, stratified again into QALB+ and QALB-, including also Neurofilament Light (NfL) and Chitinase 3-like 1 (CHI3L1) CSF concentration. RESULTS: While MIP-1α, CXCL-13, and CCL-22 CSF concentrations were higher in both MS groups compared to ONIND, in QALB+ MS CSF concentrations of CXCL-9 (17.85 ± 4.69 pg/mL), CXCL-10 (476.5 ± 324.3 pg/mL), and IL-16 (96.08 ± 86.17 pg/mL) were higher than in QALB- MS (8.98 ± 5368 pg/mL, p < 0.005, 281.0 ± 180.9 pg/mL, p < 0.05, and 47.35 ± 36.87 pg/mL, p < 0.005, respectively) and ONIND (8.98 ± 5368 pg/mlL, p < 0.005, 281.0 ± 180.9 pg/mL, p < 0.005, and 47.35 ± 36.87 pg/mL, p < 0.001, respectively). A strong correlation was observed between CXCL-9 and CXCL-10 in all MS groups (all r>0.75, all p < 0.001). In the validation cohort again CXCL-10 CSF concentration were higher in QALB+ MS than in QALB- MS (94.25 ± 64.75 vs 153.8 ± 99.52, p < 0.05), while no difference was observed in serum. CSF NfL (1642 ± 1963 vs 3231 ± 3492 pg/mL, p < 0.05) and CHI3L1 (183.9 ± 86.62 vs 262 ± 137.5 ng/mL, p < 0.05) were increased in QALB+ MS. CONCLUSIONS: BBB damage in MS is linked to a specific CSF cytokines pattern (CXCL-9, CXCL-10, IL-16), that are also involved in astrocyte-microglia interaction. To what extent their continuous production in the CNS may mark a more severe disease course merits to be investigated.

Multiple sclerosis epidemiological trends in Italy highlight the environmental risk factors.

Italy is definitely a high-risk country for multiple sclerosis (MS). Over the last 50 years, several epidemiological studies, including longitudinal surveys, have disclosed that MS incidence and prevalence in Italy mainland and Islands (Sardinia and Sicily) have progressively increased, picturing a semi-parabolic curve. Based on the comprehensive scrutiny of 58 papers, we conclude that the latitude risk gradient does not fit to the Italian map of MS. The genetic heterogeneity of the Italian ethnicities, that likely forms the basis of MS predisposition, does not account for the dramatic increase of MS incidence and prevalence observed in Italy over the last half century that, rather, seems better explained by the effect of environmental factors.

Listening to the neurological teams for multiple sclerosis: the SMART project.

OBJECTIVE: Aim of the research was to define the quality of life of Italian neurologists and nurses' professional caring for multiple sclerosis, to understand their living the clinical practice and identify possible signals of compassion fatigue. MATERIAL AND METHODS: One hundred five neurologists and nurses from 30 Italian multiple sclerosis centres were involved in an online quali-quantitative survey on the organization of care, combined with the Satisfaction and Compassion Fatigue Test and a collection of narratives. Descriptive statistics of the quantitative data were integrated with the results obtained by the narrative medicine methods of analysis. RESULTS: Most of the practitioners were neurologists, 46 average years old, 69% women, 43% part time dedicated to multiple sclerosis. An increased number of patients in the last 3 years were referred in 29 centres. Differences were found between neurologists and nurses. Physicians showed higher risks of burnout, reporting intensive working paces, lack of medical personnel, and anxiety caused by the precarious employment conditions. Nurses appeared more satisfied, although the reference to the lack of spaces, and the cross professional roles risk of compassion fatigue. Both positive and negative relationships of care were depicted as influencing the professional quality of life. CONCLUSION: The interviewed neurological teams need to limit the risk of compassion fatigue, which appeared from the first years of the career. The prevalence of the risk among neurologists suggests more awareness among scientific societies and health care managers on the risk for this category, as first step to prevent it.

Two-year real-life efficacy, tolerability and safety of dimethyl fumarate in an Italian multicentre study.

BACKGROUND: Dimethyl-fumarate (DMF) demonstrated efficacy and safety in relapsing-remitting multiple sclerosis (MS) in randomized clinical trials. OBJECTIVES: To track and evaluate post-market DMF profile in real-world setting. MATERIALS AND METHODS: Patients receiving DMF referred to Italian MS centres were enrolled and prospectively followed, collecting demographic clinical and radiological data. RESULTS: Among the 735 included patients, 45.4% were naïve to disease-modifying therapies, 17.8% switched to DMF because of tolerance, 27.4% switched to DMF because of lack of efficacy, and 9.4% switched to DMF because of safety concerns. Median DMF exposure was 17 months (0-33). DMF reduced the annual relapse rate (ARR) by 63.2%. At 12 and 24 months, 85 and 76% of patients were relapse-free. NEDA-3 status after 12 months of DMF treatment was maintained by 47.5% of patients. 89 and 70% of patients at 12 and 24 months regularly continued DMF. Most frequent adverse events (AEs) were flushing (37.2%) and gastro-enteric AEs (31.1%). CONCLUSION: Our post-market study corroborated that DMF is a safe and effective drug. Additionally, the study suggested that naïve patients strongly benefit from DMF and that DMF improved ARR also in patients who were horizontally switched from injectable therapies due to tolerability and efficacy issues.

BAFF Index and CXCL13 levels in the cerebrospinal fluid associate respectively with intrathecal IgG synthesis and cortical atrophy in multiple sclerosis at clinical onset.

BACKGROUND: B lymphocytes are thought to play a relevant role in multiple sclerosis (MS) pathology. The in vivo analysis of intrathecally produced B cell-related cytokines may help to clarify the mechanisms of B cell recruitment and immunoglobulin production within the central nervous system (CNS) in MS. METHODS: Paired cerebrospinal fluid (CSF) and serum specimens from 40 clinically isolated syndrome suggestive of MS or early-onset relapsing-remitting MS patients (CIS/eRRMS) and 17 healthy controls (HC) were analyzed for the intrathecal synthesis of IgG (quantitative formulae and IgG oligoclonal bands, IgGOB), CXCL13, BAFF, and IL-21. 3D-FLAIR, 3D-DIR, and 3D-T1 MRI sequences were applied to evaluate white matter (WM) and gray matter (GM) lesions and global cortical thickness (gCTh). RESULTS: Compared to HC, CIS/eRRMS having IgGOB (IgGOB+, 26 patients) had higher intrathecal IgG indexes (p < 0.01), lower values of BAFF Index (11.9 ± 6.1 vs 17.5 ± 5.2, p < 0.01), and higher CSF CXCL13 levels (27.7 ± 33.5 vs 0.9 ± 1.5, p < 0.005). In these patients, BAFF Index but not CSF CXCL13 levels inversely correlated with the intrathecal IgG synthesis (r > 0.5 and p < 0.05 for all correlations). CSF leukocyte counts were significantly higher in IgGOB+ compared to IgGOB- (p < 0.05) and HC (p < 0.01), and correlated to CSF CXCL13 concentrations (r 0.77, p < 0.001). The gCTh was significantly lower in patients with higher CSF CXCL13 levels (2.41 ± 0.1 vs 2.49 ± 0.1 mm, p < 0.05), while no difference in MRI parameters of WM and GM pathology was observed between IgGOB+ and IgGOB-. CONCLUSIONS: The intrathecal IgG synthesis inversely correlated with BAFF Index and showed no correlation with CSF CXCL13. These findings seem to indicate that intrathecally synthesized IgG are produced by long-term PCs that have entered the CNS from the peripheral blood, rather than produced by PCs developed in the meningeal follicle-like structures (FLS). In this study, CXCL13 identifies a subgroup of MS patients characterized by higher leukocyte counts in the CSF and early evidence of cortical thinning, further suggesting a role for this chemokine as a possible marker of disease severity.

Rituximab in the treatment of Neuromyelitis optica: a multicentre Italian observational study.

Rituximab (RTX) efficacy in NMO is suggested by several case series. No consensus exists on optimal dosing strategies. At present the treatment schedules more frequently used are 375 mg/m2/week iv for 4 weeks (RTX-A) and 1000 mg iv twice, 2 weeks apart (RTX-B). Aim of this study is to confirm RTX efficacy and safety in the treatment of NMO and to evaluate whether a most favourable dosage regimen exists. Data on RTX-treated NMO patients were collected from 13 Italian Hospitals. 73 patients (64 F), were enlisted. RTX-A was administered in 42/73 patients, RTX-B in 31/73. Median follow-up was 27 months (range 7-106). Mean relapse rate in the previous year before RTX start was 2.2 ± 1.3 for RTX-A and 2.3 ± 1.2 for RTX-B. ARR in the first year of treatment was 0.8 ± 0.9 for RTX-A and 0.2 ± 0.4 for RTX-B, in the second year of treatment was 0.9 ± 1.5 for RTX-A and 0.4 ± 0.8 for RTX-B patients (p = 0.001 for the first year, ns (0.09) for the second year). RTX-B was more effective in delaying the occurrence of a relapse (HR 2.2 (95 % IC 1.08-4.53) p = 0.02). Adverse events were described in 19/73 patients (mainly urinary tract and respiratory infections, and infusion reactions). Two deaths were reported in severely disabled patients. Though with the limitations of an observational study, our data support RTX efficacy in NMO and suggest that high dose pulses might be more effective than a more fractioned dose.

[Community-based surveillance of maternal, infant, and child (under-5) mortality in the health district of Tanguiéta (Benin) from 2006 through 2010]. / Surveillance en communauté des décès maternels et infantojuvéniles dans le district sanitaire de Tanguiéta (Bénin) de 2006 à 2010.

In Benin, maternal, infant (under 1 year) and child (under 5 years) mortality rates are measured every five years by national demographic health surveys. These provide data only at the national level, however. Because they do not reveal local disparities, they provide no information about how to target healthcare interventions. To overcome these limitations and evaluate the primary healthcare program in the Tanguieta district, the UniCredit Foundation set up a system for monitoring maternal and under-5 deaths in partnership with the local authorities. The system costs € 10,500/year, and is based on a network of 155 community healthcare workers (sentinels) responsible for counting all maternal and childhood deaths. From 2006 through 2010, the maternal mortality rate (MMR) decreased from 531 to 220 deaths per 100,000 live births; 47% of these deaths occurred at home. Mortality among children younger than 5 years (U-5) was 76 per 1,000 live births in 2006 and 77 per 1,000 live births in 2010), and 46% of the children died at home. A quality control study of our system in February 2011 showed that its sensitivity was good (95%) for MMR (232 deaths per 100,000 livebirths in 2010), but poor (48%) for U-5 mortality (155 deaths per 1,000 livebirths in 2010) and U-1 mortality (74 per 1,000 livebirths, sensitivity 47%). We conclude that the system is adequate for assessing the effect of maternal healthcare interventions but has some weaknesses in relation to childhood mortality, mainly because of local social customs and the fact that childhood deaths appear to have less resonance. Poor coverage of isolated villages may also explain this partially unsatisfactory performance. Our intervention has nonetheless contributed to improving the quality of basic data collection in the district.

Increased incidence of multiple sclerosis in the Veneto region, Italy.

BACKGROUND: To what extent the progressive increase in the incidence of multiple sclerosis (MS) observed in the province of Padova over the period 1970-1999 was an expression of a real increased risk of developing MS remained unclear. OBJECTIVE: The objective of this paper is to update the epidemiological figures of MS and probe whether the risk of having MS has increased in the province of Padova during the decade 2000-2009. METHODS: All patients born in Italy and having a diagnosis of MS or possible MS identified through analysis of all available sources of information were included in the study. The incidence and prevalence rates between 2000 and 2009 were obtained and compared with our previously published data. RESULTS: On 31 December 2009, the overall prevalence was 139.5/100,000, 192.0 ± 9.5 for females and 83.9 ± 6.3 for males. During the decade 2000-2009, the overall incidence rate of MS was 5.5 ± 0.5, 7.4 ± 0.8 for females and 3.5 ± 0.6 for males. The onset-diagnosis delay, the female/male ratio and the mean age at onset did not significantly change compared to the prior period of observation. CONCLUSION: Our findings support the hypothesis of a real increased risk of developing MS in the province of Padova. Moreover, the actual prevalence of 1.4/1000 makes our region a high-risk geographical area for MS. The role played by exogenous factors in determining susceptibility to MS needs to be thoroughly investigated.

Adverse events after endovascular treatment of chronic cerebro-spinal venous insufficiency (CCSVI) in patients with multiple sclerosis.

Although it is debated whether chronic cerebro-spinal venous insufficiency (CCSVI) plays a role in multiple sclerosis (MS) development, many patients undergo endovascular treatment (ET) of CCSVI. A study is ongoing in Italy to evaluate the clinical outcome of ET. Severe adverse events (AEs) occurred in 15/462 subjects at a variable interval after ET: jugular thrombosis in seven patients, tetraventricular hydrocephalus, stroke, paroxysmal atrial fibrillation, status epilepticus, aspiration pneumonia, hypertension with tachicardia, or bleeding of bedsore in the remaining seven cases. One patient died because of myocardial infarction 10 weeks after ET. The risk of severe AEs related to ET for CCSVI must be carefully considered.

Endovascular treatment of CCSVI in patients with multiple sclerosis: clinical outcome of 462 cases.

Although it is still debated whether chronic cerebro-spinal venous insufficiency (CCSVI) plays a role in multiple sclerosis (MS) development, many patients underwent endovascular treatment (ET) of CCSVI. The objective of the study is to evaluate the outcome and safety of ET in Italian MS patients. Italian MS centers that are part of the Italian MS Study Group were all invited to participate to this retrospective study. A structured questionnaire was used to collect detailed clinical data before and after the ET. Data from 462 patients were collected in 33 centers. ET consisted of balloon dilatation (93 % of cases) or stent application. The mean follow-up duration after ET was 31 weeks. Mean EDSS remained unchanged after ET (5.2 vs. 4.9), 144 relapses occurred in 98/462 cases (21 %), mainly in RR-MS patients. Fifteen severe adverse events were recorded in 3.2 % of cases. Given the risk of severe adverse events and the lack of objective beneficial effects, our findings confirm that at present ET should not be recommended to patients with MS.

Prognostic value of preoperative border-zone (watershed) infarcts on the early postoperative outcomes of carotid endarterectomy after acute ischemic stroke.

OBJECTIVES: To evaluate the prognostic value of cerebral border-zone infarctions (watershed infarctions) on the early postoperative outcomes of patients undergoing carotid endarterectomy (CEA) after acute ischemic stroke (AIS). METHODS: Sixty-six (66) patients with symptomatic carotid stenosis (SCS) that underwent ipsilateral CEA after AIS from January 2007 to March 2012 were included in this study. They were divided into two groups according to the topographic patterns of the stroke: group 1, Territorial Cerebral Ischemic Strokes (TCIS) caused by emboli of carotid origin; group 2, cerebral border-zone infarctions (CBZI) related to an SCS associated with hemodynamic impairment. All data was collected in a prospective database and analyzed. Outcome measures included postoperative neurological morbidity and 30-day mortality. RESULTS: Forty-three (43) patients (65.15%) experienced TCIS and were included in group 1, 23 patients (34.85%) had a CBZI and were included in group 2. There were no postoperative deaths. The postoperative neurologic morbidity rate was significantly higher in the CBZI group (22% vs. 2%, p = 0.02). Multivariate analysis demonstrates that CBZI was the only independent predictive factor of neurologic morbidity after CEA for AIS related to an SCS. Furthermore, the risk of postoperative neurologic morbidity remained significantly higher for patients with CBZI after adjustment for age, sex, initial NHISS scores, and associated contralateral carotid occlusion (HR: 0.059, 95% CI 0.004-0.85; p = 0.03). CONCLUSION: CBZIs, compared to TCIS, were associated with a higher neurological complication rate during the postoperative period after CEA for SCS in cases of AIS. Further studies are required to better define the timing and the best treatment modality for patients with CBZI related to an SCS in order to reduce associated procedural complications.

Switching therapy from natalizumab to fingolimod in relapsing-remitting multiple sclerosis: clinical and magnetic resonance imaging findings.

Clinical and/or neuroimaging evidence of disease reactivation has been described in multiple sclerosis (MS) patients after a break from natalizumab. Whether fingolimod might be a therapeutic option following natalizumab needs to be evaluated. Twenty-two relapsing remitting MS patients having JC virus antibodies (JCVAb+) in serum were shifted from natalizumab to fingolimod after a three-month washout period. Neurological evaluation with the Expanded Disability Status Scale (EDSS) was performed monthly for a mean follow-up period of nine months. In 20/22 patients, brain magnetic resonance imaging (MRI) was obtained within one month after therapy initiation. Disease reactivation was observed in 11/22 (50%) patients: clinical relapses in six patients (four patients within the first month of therapy) and MRI activity in a further five patients (three patients within the first month of therapy). Clinical and/or MRI signs suggestive of disease rebound were observed in three patients. Our data indicate that fingolimod does not exert clinical activity quickly enough to stop MS reactivation after a break from natalizumab.

Natalizumab strongly suppresses cortical pathology in relapsing-remitting multiple sclerosis.

BACKGROUND: Since cortical pathology has been indicated to play a relevant role in the physical and cognitive disability of multiple sclerosis (MS) patients, this study aims to analyze the efficacy of natalizumab in slowing down its progression. METHODS: A total of 120 relapsing-remitting MS patients completed a 2-year prospective study: 35 received natalizumab, 50 received interferon beta-1a or glatiramer acetate (immunomodulatory agents - IMA) and 35 remained untreated. Forty healthy subjects constituted the reference population. Clinical and magnetic resonance imaging (MRI) evaluations (including cortical lesions and atrophy) were performed at baseline and after 2 years. RESULTS: Natalizumab significantly reduced accumulation of new cortical lesions (0.2±0.6,range 0-3) compared to immunomodulatory agents (1.3±1.1 togli spazio, range 1-6, p=0.001) and no treatment (2.9±1.5, range 1-8, p<0.001). The percentage of patients with new cortical lesions was also lower in natalizumab-treated patients (20%) compared to IMA-treated and untreated patients (68.0% and 74.2%; p<0.001 for both comparisons). Furthermore, the progression of cortical atrophy was significantly reduced by natalizumab (% change=1.7%) compared to IMA (3.7%, p=0.003) and no therapy (4.6%, p<0.001). Finally, a greater percentage (51.4%) of natalizumab-treated patients remained disease-free (no clinical or MRI evidence of disease activity or progression) compared to IMA-treated (18%, p=0.001) and untreated patients (5.7%, p<0.001). CONCLUSIONS: Natalizumab treatment significantly decreases cortical lesion accumulation and cortical atrophy progression in severe relapsing-remitting MS. While supporting the inflammatory origin of cortical lesions, our results highlight the significant impact of natalizumab on cortical pathology.

Gray matter pathology in MS: a 3-year longitudinal study in a pediatric population.

BACKGROUND AND PURPOSE: GM pathology is considered a major determinant of disability in MS, but the comprehension of its origin and progression rate is limited by the uncertainty of dating the biologic disease onset. Thus, we planned a longitudinal study aimed at analyzing and comparing cortical pathology in pediatric and adult MS patients at clinical onset. MATERIALS AND METHODS: Within 12 months from clinical onset, 35 patients with cMS and 57 with aMS were included in a longitudinal study. At T0, GMf and CL number and volume were analyzed. Percentages of Δ-GMf and number of new CLs were assessed every year for 3 years (T1-T3). Twenty-eight age- and sex-matched NCs constituted the reference population. RESULTS: At T0, GMf did not differ between cMS and NC (P = .18), while it was lower in patients with aMS compared with both NCs (P < .001) and patients with cMS (P < .001). The number of patients with CLs, as well as CL number and volume, were higher in patients with aMS than in those with cMS (P < .001). At T3, Δ-GMf was higher in both patients with cMS (1.6% ± 0.5%; range 0.7%-3.4%; P < .001) and aMS (1.6% ± 0.6%; range 0.6%-3.4%; P < .001) compared with NCs (0.7% ± 0.2%; range 0.4%-1.1%), whereas no difference was observed between patients with cMS and aMS (P = .93). Δ-GMf significantly correlated with increased CL volume (cMS: r = 0.46; aMS: r = 0.48) and with the appearance of new CLs (cMS: r = 0.51; aMS: r = 0.49). CONCLUSIONS: Our findings suggest that focal (CLs) and diffuse (atrophy) GM damage are strictly associated with the biologic onset of MS, and proceed linearly and partly independently of WM pathology.

Technical note and results in the management of anatomical variants of renal vascularisation during endovascular aneurysm repair.

INTRODUCTION: The revascularisation of large (>3 mm) renal arteries emerging from the proximal sealing zone or off the aneurismal wall can be challenging during endovascular aortic aneurysm repair. In this article, we describe various endovascular techniques using custom-made endografts to treat these complex variant anatomies. CASES: Nine patients deemed unfit for open repair with unusual renal vascularisation associated with aortic aneurysms were treated by endovascular means. After three-dimensional (3D) reconstructions on a dedicated workstation, custom-made devices were designed and manufactured. The revascularisation of multiple renal arteries and aberrant origins of renal arteries, associated or not with pelvic kidney or horseshoe kidney, was managed using fenestrated and branched endografts. RESULTS: All target vessels were patent on computed tomography (CT) scan and contrast-enhanced ultrasound evaluation before discharge as well as on the 6-month follow-up. One patient presented a decrease of postoperative glomerular filtration rate over 30% but did not require dialysis. No sac enlargement was depicted, and no reintervention was performed during follow-up. Three type 2 endoleaks were diagnosed. CONCLUSION: Endovascular treatment with fenestrated and branched endografts should be considered in challenging renal artery anatomies in patients unfit for open repair.

Effect of disease-modifying drugs on cortical lesions and atrophy in relapsing-remitting multiple sclerosis.

OBJECTIVE: To measure the effects of disease-modifying drugs (DMDs) on the development of cortical lesions (CL) and cortical atrophy in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: RRMS patients (n = 165) were randomized to subcutaneous (sc) interferon (IFN) beta-1a (44 mcg three times weekly), intramuscular (im) IFN beta-1a (30 mcg weekly) or glatiramer acetate (GA; 20 mg daily). The reference population comprised 50 untreated patients. Clinical and MRI examinations were performed at baseline, 12 months and 24 months. RESULTS: One hundred and forty-one treated patients completed the study. After 12 months, 37/50 (74%) of untreated patients developed ≥ 1 new CL (mean 1.6), compared with 30/47 (64%) of im IFN beta-1a-treated patients (mean 1.2, p = 0.021), 24/48 (50%) of GA-treated patients (mean 0.8, p = 0.001) and 12/46 (26%) of sc IFN beta-1a-treated patients (mean 0.4, p < 0.001). After 24 months, ≥ 1 new CL was observed in 41/50 (82%) of untreated (mean 3.0), 34/47 (72%) of im IFN beta-1a-treated (mean 1.6, p < 0.001), 30/48 (62%) of GA-treated (mean 1.3, p < 0.001) and 24/46 (52%) of sc IFN beta-1a-treated patients (mean 0.8, p < 0.001). Mean grey matter fraction decrease in DMD-treated patients at 24 months ranged from 0.7 to 0.8 versus 1.0 in untreated patients (p = 0.023). CONCLUSIONS: Disease-modifying drugs significantly decreased new CL development and cortical atrophy progression compared with untreated patients, with faster and more pronounced effects seen with sc IFN beta-1a than with im IFN beta-1a or GA.

Cortical pathology in multiple sclerosis patients with epilepsy: a 3 year longitudinal study.

INTRODUCTION: The cause of epilepsy in multiple sclerosis (MS) has not yet been elucidated. The relevance of cortical pathology (cortical lesions and thickness) in MS patients with and without epilepsy was evaluated in a longitudinal study. METHODS: 32 relapsing-remitting MS patients with epilepsy (RRMS/E) and 60 matched RRMS patients without epilepsy were included in a 3 year longitudinal study. The following clinical and MR parameters were analysed: Expanded Disability Status Scale (EDSS), cognitive score (CS), cortical lesion (CL) number and volume, grey matter fraction (GMf), global cortical thickness (CTh), T2 white matter lesion volume (T2WMLV), new CLs and new WM lesions. RESULTS: At baseline (T0), CLs were observed in 27/32 (84.4%) RRMS/E and in 26/60 (43.3%) RRMS (p<0.001) patients, and the RRMS/E group had a higher number (10.2 ± 8.9 vs 4.5 ± 2.4; p<0.001) and total volume (2.0 ± 1.3 vs 0.7 ± 0.8 cm(3); p<0.001) of CLs compared with the RRMS group. No significant difference in T2WMLV was observed. Global CTh was lower in RRMS/E (2.12 ± 0.19 vs 2.35 ± 0.14 mm; p<0.001), and this group also showed a decline in cognition (CS 10.9 ± 6.3 vs 6.2 ± 3.5; p<0.001). After 3 years (T1), the RRMS/E group had a higher accumulation of new CLs (3.4 ± 3.2 vs 1.2 ± 1.1; p<0.001) and faster reduction of GMf (p=0.022) while the two groups did not differ in the number of new WM and new Gad+ lesions. DISCUSSION: RRMS/E had a more severe and rapidly evolving cortical pathology (CLs and atrophy) compared with RRMS without epilepsy. The RRMS/E group was also characterised by more pronounced cognitive decline, higher EDSS and higher prevalence of men.

Evaluation of radiation during EVAR performed on a mobile C-arm.

BACKGROUND: The aim of this study was to evaluate radiation exposure during aortic endovascular aneurysm repair (EVAR) on a mobile C-arm using a low dose and pulse mode. METHODS: We performed a retrospective analysis of a prospectively maintained database on patients undergoing EVAR. Indirect dose measurements of dose area product (DAP, mGy m²) calculated by the C-arm (OEC 9900MD), fluoroscopic time (FT), type of procedure, contrast media volume and body mass index were analysed. To confirm the correlation between direct and indirect DAP measurements, direct dose was measured with radiochromic films on a sample of 15 patients. Film grey level response was calibrated according to a reference dose measurement performed with a calibrated dosimeter. DAP and peak skin dose (PSD, Gy) were measured on each film. Correlation between DAP from direct and indirect measures, and between DAP and PSD, were analysed. RESULTS: From January 2009 to April 2011, 335 patients underwent EVAR. Complete data were available on 301 procedures including 188 bifurcated, 54 fenestrated, 28 thoracic, 20 branched and 11 aorto-uni-iliac endografts implantation. The respective median FT and DAP was 9.36 min (1.8-67) and 3 mGy m(2) (0.4-28); 27.2 min (2-69) and 7.3 mGy m(2) (1.2-29); 7.75 min (1.2-19.1) and 2 mGy m(2) (0.3-11); 42.98 min (2.4-95.4) and 15.95 mGy m(2) (2.98-77.7); 6.2 min (0.5-36.3) and 2 mGy m(2) (0.3-11). Direct DAP measurement on radiochromic films was strongly correlated with DAP values provided by the C-arm (r = 0.98). PSD correlated weakly with DAP. DAP was significantly increased (p < 0.001) in patients with a body mass index >30. Contrast media volume was significantly increased in the branched endograft group. CONCLUSION: Indirect DAP values measured by the C-arm are accurate to evaluate radiation exposure. Compared to the literature, our values for standard procedures are significantly decreased by the usage of low dose and pulse mode. DAP for fenestrated and branched procedures was comparable to published DAP values with standard procedures using a regular fluoroscopic mode.

Single-centre prospective comparison between contrast-enhanced ultrasound and computed tomography angiography after EVAR.

AIM: To evaluate contrast-enhanced ultrasound (CEUS) as an effective alternative to CT-angiography (CTA) for endoleak detection and aneurismal sac diameter measurement in the follow-up after endovascular abdominal aortic aneurysm repair (EVAR). METHODS: From January 2006 to December 2010, 395 patients underwent EVAR follow-up with both CTA and CEUS. The diameter of the aneurismal sac and the presence of endoleaks were evaluated in all the 395 paired examinations. RESULTS: Bland-Altman plots showed a good agreement in aneurismal sac diameter evaluation between the two imaging modalities. The mean diameter was 54.93 mm (standard deviation (SD) ±12.57) with CEUS and 56.01 mm (SD ± 13.23) with CTA. The mean difference in aneurismal sac diameter was -1.08 mm ± 3.3543 (95% confidence interval (CI), -0.75 to -1.41), in favour of CTA. The number of observed agreement in endoleak detection was 359/395 (90.89%). The two modalities detected the same type I and type III endoleaks. McNemar's χ(2) test confirmed that CTA and CEUS are equivalent in endoleak detection. CONCLUSIONS: CEUS demonstrated to be as accurate as CTA in endoleak detection and abdominal aortic aneurysm diameter measurements during EVAR follow-up, without carrying the risks of radiation exposure or nephrotoxicity. Even if it cannot be proposed as the sole imaging modality during follow-up, our analysis suggests that it should have a major role.

Progressive multiple sclerosis is not associated with chronic cerebrospinal venous insufficiency.

OBJECTIVE: Chronic cerebrospinal venous insufficiency (CCSVI) had been suggested to play a major pathogenetic role in multiple sclerosis (MS), but recent data on early stages of MS have not confirmed this theory. Nonetheless, CCSVI could represent a late phenomenon of MS or be associated with progression of disability. Thus, we studied CCSVI prevalence in primary progressive (PP) and secondary progressive (SP) MS, to clarify whether CCSVI characterizes the progressive forms of this disease. METHODS: A total of 35 patients with SPMS, 25 patients with PPMS, and 60 age- and gender-matched normal controls (NC) were enrolled into a cross-sectional study. Extracranial and transcranial high-resolution venous echo color Doppler sonography (ECDS-TCDS) was performed in all patients and NC. Those patients having any abnormal ultrasound finding were asked to undergo selective venography (VGF). RESULTS: Patients with PPMS (11 women, 14 men; mean age 47 ± 11 years) had a disease duration of 11 ± 7 years and Expanded Disability Status Scale (EDSS) score of 6.0 ± 0.5. Patients with SPMS (22 women, 13 men; mean age 45 ± 14.5 years) had a disease duration of 18 ± 14 years and EDSS score of 6.0 ± 0.8. TCDS was normal in all patients. ECDS showed one or more abnormal findings in 9/60 (15.0%) patients (7/35 [20.0%] SPMS, 2/25 [8.0%] PPMS) and in 14/60 (23.3%) NC (p not significant for all comparisons). CCSVI criteria were fulfilled in 0 NC and 4 (6.7%) patients with MS: 3 SPMS and 1 PPMS. VGF, performed in 6/9 patients, was abnormal only in one case who had bilateral internal jugular vein stenosis. CONCLUSION: Our findings indicate that CCSVI is not a late secondary phenomenon of MS and is not associated with disability.