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Objectives: To report on multiple sclerosis (MS) incidence in Brittany, north-western France., Materials & Methods: From 2000, we set up a population-based register for patients presenting a putative incident MS (PIMS), that is first symptoms compatible with MS onset. We used 3 medical sources of case ascertainment (neurologists, CSF, regional MS-Clinic). Eligibility criteria required both clinical onset and being permanent resident of Brittany in 2000 or 2001. From 2010, all medical records were tracked, the 10-year follow-up allowing previously reported data to be updated., Results: Of 313 eligible PIMS, there were 208 definite MS (both McDonald and Poser criteria), 41 CIS-probable MS (Poser criteria), 32 CIS-possible MS and 32 non-MS. Our incident cohort of 249 MS cases with definite/probable MS (sex ratio 2.95) gave a crude annual incidence of 4.28 per 100,000 inhabitants (6.22 for women, 2.23 for men), and age-standardized rates (adjustment to the European population) of 4.41 [3.32-5.51], 6.68 [4.75-8.60], and 2.21 [1.12-3.31], respectively. Age-specific rates by gender and initial course showed that attack onset MS peaked at 25-29 years and progressive onset MS at 40-44 years in women (20-24 years and 45-49 years in men, respectively)., Conclusions: Brittany is confirmed a high-risk region for MS. Our data show marked differences in sex-specific pattern of MS incidence by clinical course and point out 25- to 29-year-old women as having the highest MS risk. While temporal variations cannot be excluded, comparison with overall French data suggests that other factors rather than latitude may influence the MS risk in France., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Purpose: Multiple sclerosis (MS) prognosis remains a challenge for both patients and physicians. Complementary to natural history studies, updated population-based data from the first event suggestive of MS, at the time of the first approved disease modifying drug (DMD), are needed. Our objective was to provide a 10-year history of MS from clinical onset at time of first approved DMDs in a population-based cohort., Methods: A population-based cohort of patients whose first clinical event suggestive of MS had occurred in Brittany between 2000 and 2001 was prospectively selected. History of relapses, treatments and disability up to 10 years after onset were collected., Results: In all, 278 patients with either attack-onset (n = 244) or progressive-onset (n = 34) were recruited. Amongst attack-onset patients, 30% remained as clinically isolated syndrome and 70% had a second relapse after a median time of 1.7 years (95% confidence interval 1.2-2.4). 80% of relapsing-remitting MS patients received DMDs for at least 6 months. 29% reached disability status scale (DSS) 3 and 8% DSS 6. Amongst progressive-onset patients, 100% reached DSS 3 and 59% DSS 6., Conclusion(s): Our population-based study reports a lower risk of disability progression at 10-year follow-up in the relapsing-remitting MS group than previously reported. This better prognosis was not observed in the progressive-onset MS group. This finding impacts the prognosis given to patients in clinical practice., (© 2014 EAN.)

Objective: The purpose of this study was to describe the patterns of psychotropic drug use in a large representative population of children and adolescents drawn from the French National Health Insurance databank., Methods: Data were drawn from a sample of 1% of the beneficiaries of the French national health insurance, selecting those 0-17 years old in 2010 (n=128,298). In addition to age and gender, data included the identification number of each drug allowing a European Pharmaceutical Marketing Research Association (EphMRA) classification, as well as the type of the prescriber., Results: Overall, 2.5% of children and adolescents had been prescribed psychotropic medication. A majority were prescribed anxiolytics (1.9%), followed by antidepressants (0.3%), antipsychotics (0.3%), and stimulants (0.2%). Between the ages of 15 and 17, 6.1% of girls were prescribed anxiolytics and 1.1% were prescribed antidepressants. For boys, the anxiolytics remained the most prescribed psychotropic medication; however, between the ages of 11 and 14, and between the ages of 15 and 17 they received more antipsychotics (0.7% and 0.8%) and between the ages of 6 and 10, and between the ages of 11 and 14 (0.7% and 0.6%), they were prescribed more stimulants than were girls. Among those who received a prescription, a majority of youth (84.6%) received only one class of drugs, and general practitioners were found to be prescribing most of these prescriptions (81.7%)., Conclusions: The prevalence of psychotropic drug use in France is similar to that of the Netherlands and much lower than what is observed in the United States. Stimulants are less frequently prescribed in France than in other European countries, but anxiolytics are prescribed considerably more in France than in any other country.

Studies have linked the use of corporal punishment of children to the development of mental health disorders. Despite the recommendation of international governing bodies for a complete ban of the practice, there is little European data available on the effects of corporal punishment on mental health and the influence of laws banning corporal punishment. Using data from the School Children Mental Health Europe survey, the objective of this cross-sectional study was to examine the prevalence and legal status of corporal punishment across six European countries and to evaluate the association between parental use of corporal punishment and children's mental health. The study found that odds of having parents who reported using occasional to frequent corporal punishment were 1.7 times higher in countries where its use is legal, controlling for socio-demographic factors. Children with parents who reported using corporal punishment had higher rates of both externalized and internalized mental health disorders.

Our study aimed to describe safety and neurological impact of alemtuzumab as last-line rescue therapy in aggressive multiple sclerosis (MS) patients, previously treated by Mitoxantrone (MITOX). Between June 2004 and October 2013, 13 patients received alemtuzumab at 20 mg/day and 3 at 12 mg/day for 5 days. EDSS, relapses, secondary progression were prospectively assessed 12 and 6 months before treatment, at baseline and every 3 months. Mean follow-up was 6.2 years [1-10]. Mean age at alemtuzumab start was 40 years [26-49] for 8 Secondary Progressive (SP) and 30 years [26-35] for 8 Relapsing-Remitting (RR) patients. MS duration was 13.7 (± 3) and 8.3 (± 4) years, respectively. During the 12 months before alemtuzumab, annual relapse rate was 0.75 and 3.14, respectively and the 16 patients accumulated 2-30 new gadolinium enhancing lesions. 4 patients (suboptimal responders) received alemtuzumab during MITOX and 12 patients 1-7.8 years after MITOX. Out of 8 SPMS, 2 were disease free up to last visit (4.7 and 8 years), 5 improved or stabilized but only transiently and 1 worsened. Out of 8 RRMS, 1 remained stable up to last visit (8.7 years) despite 1 relapse and active MRI at 18 months and 7 improved (1-4 point EDSS): 4 remained disease free up to last visit (12, 24, 38 months and 7 years), 2 were successfully retreated at 25 and 33 months and 1 worsened progressively 24 months after alemtuzumab. 2 patients developed Grave's disease and 1 hypothyroidism. Alemtuzumab controls aggressive RRMS despite previous use of MITOX.

The introduction of the McDonald criteria has enabled earlier diagnosis of multiple sclerosis (MS). However, even with the 2010 revised criteria, nearly 50% of patients remain classified as "possible MS" following the first MRI. The present study aimed to demonstrate that time to MS diagnosis could be shorter than 2010 revised criteria, and established after a single early MRI in most patients with the association of the symptomatic lesion and at least one suggestive asymptomatic lesion. We also evaluated the short-term predictive capacity of an individual suggestive lesion on disease activity. We analyzed initial MRI results from 146 patients with MS from a multicenter retrospective study. Visualization of the symptomatic lesion was used as a primary criterion. Secondary criteria included one suggestive lesion (SL) aspect or topography on MRI, or one non-specific lesion associated with positive CSF. The proposed criteria led to a positive diagnosis of MS in 100% of cases, from information available from the time of the first MRI for 145 patients (99.3%). At least one SL was observed for 143 patients (97.9%), and positive CSF for the 3 others. Compared to the McDonald criteria, the proposed criteria had 100% sensitivity, with a significantly shorter mean time to reach a positive diagnosis. Furthermore, the simultaneous presence of corpus callosum, temporal horn, and ovoid lesions was associated with radiological or clinical activity after a year of follow-up. The proposed diagnostic criteria are easy to apply, have a good sensitivity, and allow an earlier diagnosis than the 2010 McDonald criteria. Nevertheless, prospective studies are needed to establish specificity and to confirm these findings.

Background: Neighbourhood deprivation has been shown to be inversely associated with mortality 1 month after stroke. Whether this disadvantage begins while patients are still receiving acute care is unclear. We aimed to study mortality after stroke specifically in the period while patients are under acute care and the ensuing period when they are discharged to home or other care settings., Methods: Our sample includes 1760 incident strokes (mean age 75, 48% men, 86% ischaemic) identified between 1998 and 2010 by the population-based stroke registry of Dijon (France). We used Cox regression to study all-cause mortality up to 90 days after stroke occurrence., Results: Overall, 284 (16.1%) patients died during the 90 days following stroke. Prior to stroke, risk factors prevalence (eg, high blood pressure and diabetes) and acute care management did not vary across deprivation levels. There was no association between deprivation and mortality while patients were in acute care (HR comparing the highest to the lowest tertiles of deprivation: 1.01, 95% CI 0.71 to 1.43). After discharge, however, age and gender adjusted mortality gradually increased with deprivation (HR 2.08, 95% CI 1.07 to 4.02). This association was not modified when stroke type and severity were accounted for., Conclusions: The gradient of higher poststroke mortality with increasing neighbourhood deprivation was noticeable only after acute hospital discharge. Quality of postacute care and social support are potential determinants of these variations., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background and Purpose: This study compared three different combinations of DWI parameters: three and six diffusion imaging directions (3dir and 6dir, respectively) using b=1000 or 2000 s/mm(2) (b1000 or b2000, respectively) to improve detection of recent ischemic lesions at 3 Tesla (3 T)., Materials and Methods: A total of 47 consecutive patients underwent three DWI scans: 3dir b1000; 6dir b1000; and 6dir b2000. Qualitative visual analysis was performed by three readers based on evaluation of the number of lesions, presence of artifacts and diagnostic confidence. Interobserver agreement, sensitivity, specificity, and positive and negative predictive values were calculated., Results: Forty-five lesions were detected by 3dir b1000, 52 by 6dir b1000 and 56 by 6dir b2000 in 30 patients. The additional lesions identified by 6dir b2000 were either small or located in the posterior fossa. Sensitivity with 6dir b2000 was significantly higher than with 3dir b1000 (98.1% vs 77.4%; P<0.05)., Conclusion: At 3 T, 6dir b2000 DWI detected more acute ischemic lesions than 3dir b1000, particularly small lesions and those located in the brain stem., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Background and Objective: Management of transient ischemic attacks (TIAs) is of vital importance in an attempt to prevent stroke. However, suboptimal management still raise concern among general practitioners (GPs) and emergency department (ED) physicians-the first medical contact of most TIA patients. This may relate to their poorly updated knowledge about TIA. The study was designed to assess knowledge of TIA among these non-neurologists., Methods: The study was a post-mailed questionnaire survey among GPs and ED physicians. The questionnaire related to selective clinical aspects on TIA., Results: There were a total of 85 respondents for analysis, mostly GPs (n=64; 75.3%), out of 177 mailed physicians. Response rate was 52.7%. Many of these respondents were unaware of the newly proposed TIA definition (59%), unfamiliar with TIA mimics and predictors of post-TIA early stroke recurrence and therefore with the rationales underlying the need of emergency management of TIA. More than one third (39%) were unaware of the relevant national guidelines. Guidelines-aware respondents performed better in most part of the mailed questionnaire., Conclusion: Our results show that poorly updated knowledge about TIA among non-neurologists represents a potential contributing factor to the persisting sub-optimal management of the disorder. Although further studies are needed to confirm this, improved continuous medical education of this group of health care professionals appears warranted., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Introduction: After multiple-ligament injuries and dislocations of the knee, clinical assessment of the soft tissues is difficult and MRI is generally performed., Hypothesis: MRI is a reliable examination, providing a precise and reproducible assessment of soft-tissue lesions after multiple-ligament injuries or dislocations of the knee., Materials and Methods: Forty patients presenting multiple-ligament lesions of the knee were included in this multicenter prospective study. All had an MRI of the knee in the 48 h following their accident. Thirty-four patients were treated surgically. A 17-item standardized interpretation guide was created. Intraobserver reproducibility was assessed by comparing the interpretations of five surgeons at two different times 3 weeks apart. Interobserver reproducibility was evaluated by comparing the results of the interpretations of 40 MRIs performed by three pairs of surgeons. The relevance of the MRI interpretations was determined by comparing the results of the surgeons to those of a radiologist and with the data from the surgical reports., Results: The overall intraobserver and interobserver agreement was low. Comparing the surgeon's results with the radiologist's results and the surgical data, the agreement was low., Discussion: After multiple-ligament injuries and dislocations of the knee, a precise diagnosis is necessary. This study provides an isolated demonstration of the lack of precision and reproducibility of MRI interpretations for the diagnosis of the lesion's topography. MRI should be integrated into a complete assessment with a precise clinical exam and stress X-rays., Level of Evidence: Level IV, prospective case-control study., (Copyright © 2013. Published by Elsevier Masson SAS.)

Background: Benign multiple sclerosis (BMS) is a controversial concept which is still debated. However identification of this kind of patients is crucial to prevent them from unnecessary exposure to aggressive and/or long term medical treatments., Objectives: To assess two definitions of 'clinically definite benign multiple sclerosis' (CDBMS) using long-term follow-up data, and to look for prognostic factors of CDBMS., Methods: In 874 patients with definite relapsing-remitting MS, followed up for at least 10 years, disability was assessed using the Disability Status Scale (DSS). CDBMS was defined by either DSS score≤2 (CDBMS1 group) or DSS score≤ 3 (CDBMS2 group) at 10 years. We estimated the proportion of patients who were still benign at 20 and 30 years after clinical onset., Results: CDBMS frequency estimates were 57.7% and 73.9% when using CDBMS1 and CDBMS2 definitions, respectively. In the CDBMS1 group, only 41.7% (105/252) of cases were still benign 10 years later, and 41.1% (23/56) after an additional decade, while there were 53.8% (162/301) and 59.5% (44/74) respectively in the CDBMS2 group., Conclusions: This 30-year observational study, which is one of the largest published series, indicates that favourable 10-year disability scores of DSS 2 or 3 fail to ensure a long-term benign course of multiple sclerosis. After every decade almost half of the CDBMS were no longer benign. CDBMS, as currently defined, is an unwarranted conceptual hodgepodge. Other criteria using new biomarkers (genetic, biologic or MRI) should be found to detect benign cases of MS.

Background: The efficacy of continuous subcutaneous apomorphine infusion (APO) has been evaluated in advanced Parkinson's disease in several open-label studies but never in a population of patients for whom subthalamic nucleus deep brain stimulation (STN-DBS) was contraindicated., Methods: The aim of this study was to evaluate the efficacy and cognitive safety of APO at 12-month follow-up in 23 advanced parkinsonian patients (mean age: 62.3 years; mean disease duration: 13.9 years) whose dopa-resistant axial motor symptoms and/or cognitive decline constituted contraindications for STN-DBS. Their motor and cognitive status were evaluated before APO and 12 months afterwards., Results: After one year, patients expressed high levels of satisfaction, with a mean rating on the Visual Analog Scale of 52.8% under APO. Daily OFF time, recorded in a 24-h diary, was reduced by 36% and ON time improved by 48%. There was a significant reduction (-26%) in mean oral levodopa equivalent dose. Dopa-resistant axial symptoms and neuropsychological performance remained stable. No adverse event was noted and none of the patients needed to take clozapine at any time., Conclusions: APO is both safe and effective in advanced parkinsonian patients with untreatable motor fluctuations, for whom STN-DBS is contraindicated due to dopa-resistant axial motor symptoms and/or cognitive decline. As such, it should be regarded as a viable alternative for these patients., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objectives: The long-term impact of interferon-beta-1b (IFN) might be improved by short-term immunosuppression with mitoxantrone (MITOX) in aggressive relapsing-remitting multiple sclerosis (ARMS) patients., Methods: In this 3-year clinical and MRI study, 109 ARMS patients (two or more relapses in the previous 12 months and one or more gadolinium (Gd)-enhancing MRI lesion) were randomised into two groups: 54 patients received MITOX monthly (12 mg/m(2); maximum 20 mg) combined with 1 g of methylprednisolone (MP) for 6 months followed by IFN for the last 27 months, and 55 patients received IFN for 3 years combined with 1 g of MP monthly for the first 6 months. The primary endpoint was the time to worsen by at least one Expanded Disability Status Scale point confirmed at 3 months., Results: The time to worsen by at least one Expanded Disability Status Scale point confirmed at 3 months was delayed by 18 months in the MITOX group compared with the IFN group (p<0.012). The 3-year risk of worsening disability was reduced by 65% in the MITOX group relative to the IFN group (11.8% vs 33.6%). MITOX patients had a reduced relapse rate by 61.7%, a reduced number of Gd-enhancing lesions at month 9 and a slower accumulation of new T2 lesions at each time point., Conclusions: Although there were limitations in this investigator-academic-driven study, the data do suggest that mitoxantrone induction therapy prior to INF beta-1b may have a role in aggressive disease.

Background: In order to reduce the risk of progressive multifocal leucoencephalopathy when using natalizumab for more than 12 months, a 6-month drug holiday has been discussed. However, the consequences on short term disease activity have been poorly assessed., Objective: The aim of this study was to assess clinical and radiological disease activity within 6 months after stopping natalizumab in very active relapsing remitting Multiple Sclerosis (RRMS) patients., Methods: In 8 hospitals from Western France, we retrospectively collected clinical and MRI data from consecutive RRMS patients treated with natalizumab for at least 6 months, and who stopped the drug for various reasons except therapeutic failure. Patients didn't receive any other disease modifying treatment after discontinuing natalizumab., Results: A total of 27 patients with very active RRMS before natalizumab start (mean annualized relapse rate of 2.3, MRI activity in 21 of 27 patients) were studied. Within 6 months after discontinuing natalizumab, 18 patients (67%) experienced clinical relapse and 3 additional patients had radiological activity, without clinical relapse. Four patients (15%) experienced a rebound activity, with severe relapse and 20 or more gadolinium enhancing lesions on MRI., Conclusion: Such observational data didn't support the concept of drug holiday when using natalizumab in very active RRMS., (Copyright © 2011. Published by Elsevier B.V.)

Purpose: Only a few European countries have carried out large, community-based, national surveys about psychiatric morbidity. Here is presented the first national French survey, aiming to estimate the prevalence of anxiety disorders and associated comorbidities according to sociodemographic characteristics., Materials and Methods: The Mental Health in General Population (MHGP) database is derived from a representative national survey of the French adult population (n=36,105), conducted between 1999 and 2003. Data collection was done using an anonymous face-to-face interview. The presence of anxiety disorders (generalized anxiety disorder, panic disorder, agoraphobia, social phobia and post-traumatic stress disorder) was assessed using the Mini International Neuropsychiatric Interview., Results: The overall prevalence of anxiety disorders was estimated to be 21.6%, generalized anxiety disorder being the most prevalent one (12.8%). Women, young people, and people earning low income were identified as the more at risk. Major depressive episode, alcohol abuse and drug addiction frequently co-occur with anxiety disorders (28.3, 4.4 and 2.8% respectively)., Conclusion: The MHGP study showed that anxiety disorders are highly prevalent in France with a high frequency of comorbidities. Our results highlight the need for considering anxiety disorders as a public health priority in France as well as in other European countries., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Several clinical courses have been defined in multiple sclerosis (MS), but uncertainty remains as to whether they reflect different neuropathological mechanisms. Two recent concepts have emerged which could influence the treatment strategy adopted in MS: inflammation drives axonal damage; disability progression in MS follows a two-stage process., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Background: From 2001, a French multicentre study was conducted prospectively in a large cohort of MS patients and annually updated up to at least 5 years after initiation of MITOX therapy., Objective: To determine long-term safety profile of mitoxantrone (MITOX) in multiple sclerosis (MS)., Methods: Eight hundred and two patients from 12 MS centres (308 relapsing-remitting, 352 secondary progressive and 142 primary progressive) received MITOX monthly for 6 months (87%) or every 3 months (13%). Patients underwent clinical and haematologic evaluations before every MITOX infusion and every 6-12 months up to 5 years after MITOX start. Echocardiograms were performed at the start and end of MITOX and up to 5 years after., Results: The cohort was followed for 5354 patient-years (mean). One out of 802 patients (0.1%) presented with acute congestive heart failure and 39 out of 794 patients (4.9%) presented with asymptomatic left ventricular ejection fraction reduction under 50% (persistent in 11 patients (28%), transient in 27 patients (69%), on the last scan at year 5 in 1 patient). Two cases of therapy-related leukaemia (0.25%) were detected 20 months after MITOX start (one death and one with 8 years confirmed remission). Of the 317 women treated before the age of 45, 17.3% developed a persistent age-dependant amenorrhea., Conclusion: This large cohort with at least 5 years of follow-up provided good insights into the long-term safety profile of MITOX in MS.

Objective: Major depressive disorder (MDD) is associated with abnormalities in the recognition of emotional stimuli. MDD patients ascribe more negative emotion but also less positive emotion to facial expressions, suggesting blunted responsiveness to positive emotional stimuli. To ascertain whether these emotional biases are modality-specific, we examined the effects of MDD on the recognition of emotions from voices using a paradigm designed to capture subtle effects of biases., Methods: Twenty-one MDD patients and 21 healthy controls (HC) underwent clinical and neuropsychological assessments, followed by a paradigm featuring pseudowords spoken by actors in five types of emotional prosody, rated on continuous scales., Results: Overall, MDD patients performed more poorly than HC, displaying significantly impaired recognition of fear, happiness and sadness. Compared with HC, they rated fear significantly more highly when listening to anger stimuli. They also displayed a bias toward surprise, rating it far higher when they heard sad or fearful utterances. Furthermore, for happiness stimuli, MDD patients gave higher ratings for negative emotions (fear and sadness). A multiple regression model on recognition of emotional prosody in MDD patients showed that the best fit was achieved using the executive functioning (categorical fluency, number of errors in the MCST, and TMT B-A) and the total score of the Montgomery-Asberg Depression Rating Scale., Conclusions: Impaired recognition of emotions would appear not to be specific to the visual modality but to be present also when emotions are expressed vocally, this impairment being related to depression severity and dysexecutive syndrome. MDD seems to skew the recognition of emotional prosody toward negative emotional stimuli and the blunting of positive emotion appears not to be restricted to the visual modality., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: High-frequency bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) is a promising treatment in refractory obsessive-compulsive disorder (OCD)., Method: Using the crossover, randomized, and double-blind procedure adopted by the STOC study, 10 patients treated with high-frequency bilateral STN DBS underwent am 18-fluorodeoxyglucose positron emission tomography (PET) investigation to highlight the neural substratum of this therapeutic approach., Results: The median Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores for all 10 patients were 31 (minimum = 18, maximum = 36) with "Off-Stimulation" status and 19 (minimum = 0, maximum = 30) with "On-Stimulation" status (p = .05). The OCD patients in Off-Stimulation status showed a hypermetabolism in the right frontal middle and superior gyri, right parietal lobe, postcentral gyrus, and bilateral putamen compared with healthy control subjects. A significant decrease in cerebral metabolism was observed in the left cingulate gyrus and the left frontal medial gyrus in On-Stimulation conditions compared with Off-Stimulation conditions. In addition, the improvement assessed by Y-BOCS scores during the On-Stimulation conditions was positively correlated with PET signal changes at the boundary of the orbitofrontal cortex and the medial prefrontal cortex, between PET signal changes and the Y-BOCS scores modifications in On-Stimulation status., Conclusion: This study suggests that the therapeutic effect of STN DBS is related to a decrease in prefrontal cortex metabolism., (Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Aim: The purpose of this study was to measure the bone mineral density (BMD) of children with Crohn's disease (CD) and to prospectively assess its evolution., Patients and Methods: A total of 27 children (20 boys, seven girls), aged 12.1±2.5 years, were recruited at the time of CD diagnosis. Dual-energy X-ray absorptiometry (DEXA) was used to measure BMD, expressed as Z scores for chronological age (BMD/CA) and bone age (BMD/BA). One year later, BMD was measured again to identify any correlations with disease activity [group A (active disease) vs group R (remission)]., Results: BMD/CA and BMD/BA were negatively correlated with delay in diagnosis (P<0.0001 and P<0.05, respectively). BMD/CA was less than -2 standard deviation (SD) in nine patients and BMD/BA was less -2 SD in four patients. At the follow-up, the increase in BMD was smaller in group A (n=14), whether expressed as absolute values (-0.002 vs 0.040 g/cm(2) per year; P<0.024) or as percentages (-0.2 vs 6.6%; P<0.041); changes in BMD/CA (-0.5 vs -0.1 SD/year) and BMD/BA (-0.3 vs 0 SD/year) did not differ., Conclusion: Diagnostic delay greatly affects BMD in children with CD even prior to corticosteroid therapy. The risk of low BMD increases with persistent CD activity, although the risk is reduced in association with bone maturation delay., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Hand hygiene compliance was evaluated by direct observation in 2006 and 2007. In 2007, data on characteristics such as job seniority, hand hygiene education, and patient-to-nurse ratio during direct observations were collected. A hand hygiene promotional programme was performed between the two evaluations. Univariate and multivariate analysis identified factors associated with improved hand hygiene compliance. Between 2006 and 2007, from 761 hand hygiene opportunities, overall and partial compliance improved from 44.9% to 58% (P<0.001) and from 73.5% to 88.4% (P<0.001), respectively. In 2007, improvements in hand hygiene overall or partial compliance were seen when senior healthcare workers (HCWs) were present in the clinical area under investigation (P=0.04 or P=0.08, respectively). Partial hand hygiene compliance was significantly better in 2007 after a hand hygiene educational programme had been presented (P<0.015). Similar rates of compliance were observed whatever the patient-to-nurse ratio during the observation. Multivariate analysis identified job seniority as an independent predictor of hand hygiene compliance. Our results suggest that hand hygiene compliance is influenced by education on hand hygiene and that a senior HCW could act as a role model for other HCWs. These data should be considered when developing future hygiene interventions., (Copyright 2010 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved.)

It is well documented that disability accumulation in multiple sclerosis is correlated with axonal injury and that the extent of axonal injury is correlated with the degree of inflammation. However, the interdependence between focal inflammation, diffuse inflammation and neurodegeneration, and their relative contribution to clinical deficits, remains ambiguous. A hypothesis might be that early focal inflammation could be the pivotal event from which all else follows, suggesting the consideration of multiple sclerosis as a two-stage disease. This prompted us to define two phases in the disease course of multiple sclerosis by using two scores on the Kurtzke Disability Status Scale as benchmarks of disability accumulation: an early phase, 'Phase 1', from multiple sclerosis clinical onset to irreversible Disability Status Scale 3 and a late phase, 'Phase 2', from irreversible Disability Status Scale 3 to irreversible Disability Status Scale 6. Outcome was assessed through five parameters: Phase 1 duration, age at Disability Status Scale 3, time to Disability Status Scale 6 from multiple sclerosis onset, Phase 2 duration and age at Disability Status Scale 6. The first three were calculated among all patients, while the last two were computed only among patients who had reached Disability Status Scale 3. The possible influence of early clinical markers on these outcomes was studied using Kaplan-Meier estimates and Cox models. The analysis was performed in the Rennes multiple sclerosis database (2054 patients, accounting for 26,273 patient-years) as a whole, and according to phenotype at onset (1609 relapsing/445 progressive onset). Our results indicated that the disability progression during Phase 2 was independent of that during Phase 1. Indeed, the median Phase 2 duration was nearly identical (from 6 to 9 years) irrespective of Phase 1 duration (<3, 3 to <6, 6 to <10, 10 to <15, >or=15 years) in the whole population, and in both phenotypes. In relapsing onset multiple sclerosis, gender, age at onset, residual deficit after the first relapse and relapses during the first 2 years of multiple sclerosis were found to be independent predictive factors of disability progression, but only during Phase 1. Our findings demonstrate that multiple sclerosis disability progression follows a two-stage process, with a first stage probably dependent on focal inflammation and a second stage probably independent of current focal inflammation. This concept has obvious implications for the future therapeutic strategy in multiple sclerosis.

Fatigue is one of the most common and disabling symptoms of multiple sclerosis (MS) and has a significant, often underestimated, impact on patients' quality of life. Current management is mainly symptomatic. 3,4-diaminopyridine (3,4-DAP) is a voltage-dependent potassium channel blocker that has been used on a named patient basis in Europe for many years to improve motor function and fatigue in patients with MS and other neuromuscular disorders, and it is undergoing the European approval process for Lambert-Eaton myasthenic syndrome (LEMS). The efficacy and safety of 3,4-DAP as symptomatic therapy in MS have not been widely evaluated. This study aimed to assess the safety profile of 3,4-DAP in routine clinical practice in an observational, retrospective study. The study involved 669 patients of the Rennes Multiple Sclerosis Clinic, France, who were treated with 3,4-DAP for the relief of fatigue during the period 1998-2003. Overall, 18.2% of patients presented adverse drug reactions (ADRs) while using moderate doses of 3,4-DAP (20-30 mg daily or up to 80 mg daily for patients with LEMS) for periods of up to 51 months. The majority of ADRs were mild to moderate and transient or reversible at the end of treatment (mean treatment duration = two months) or after dose adjustment. Most did not require discontinuation. The most commonly observed ADRs were paraesthesias. There was one case of epileptic seizure, one of hepatotoxicity and one of heart palpitations thought 'possibly' to be linked to 3,4-DAP. These underline the need for continued monitoring during treatment with 3,4-DAP.

Objective: To evaluate parental stress after a false-positive result at the time of the cystic fibrosis (CF) newborn screening (NBS), attributable to heterozygotism or persistent hypertrypsinemia., Study Design: A prospective study was conducted in 86 French families at 3, 12, and 24 months after NBS. A psychologist conducted interviews with a questionnaire, the Perceived Stress Scale, and the Vulnerable Child Scale., Results: Overall, 96.5% of parents said they had been anxious at the time of the sweat test. However, 86% felt entirely reassured 3 months after the test. The mean Perceived Stress Scale score did not differ from that observed in the French population. Mean Vulnerable Child Scale scores were high, associated with a low Parental Perception of Child Vulnerability. These results did not differ significantly at 1 and 2 years. In total, 86% to 100% of families no longer worried about CF. All parents stated that they would have the test performed again for another child., Conclusions: CF NBS can lead to false-positive results, causing parental anxiety, which quickly decreases after a sweat test performed soon after the phone call.

Background and Study Aim: A video capsule similar to that used in small-bowel capsule endoscopy is now available for esophageal exploration. The aim of our study was to compare the accuracy of upper endoscopy (esophageal gastroduodenoscopy [EGE]) with esophageal capsule endoscopy (ECE) in patients at risk of esophageal squamous cell cancer (SCC)., Patients and Methods: 68 patients at risk of SCC secondary to a history of head and neck neoplasia were included in this comparison of techniques for detecting SCC and dysplasia. ECE was done using the first generation Pillcam ESO and EGE was performed in accordance with the usual practice of each center, followed by examination with 2 % Lugol staining and biopsy of unstained areas (39 neoplasia comprising 5 low grade dysplasia, 8 high grade dysplasia and 26 SCC)., Results: Compared with EGE with and without Lugol staining, the sensitivities of ECE for neoplasia diagnosis were 46 % and 54 %, respectively. On a per-patient basis, the sensitivity, specificity, and positive and negative predictive value of ECE were 63 %, 86 %, 77 % and 76 %, respectively, compared with EGE without staining, and 61 %, 86 %, 77 % and 73 % compared with EGE with iodine staining. Neither the ECE transit time nor the distance between the esopharyngeal line and the neoplastic lesion differed between the 21 false-negative and 18 true-positive cases diagnosed by ECE; the only difference was a smaller median diameter among false negatives ( P < 0.001)., Conclusion: In a cohort at high risk for esophageal SCC, ECE is not sensitive enough to diagnose neoplastic lesions., ((c) Georg Thieme Verlag KG Stuttgart . New York.)

Background: There are few data about the performance variability among endoscopists participating to nationwide or regionwide colorectal cancer screening programs., Objective: To assess the variability of neoplasia detection rates among endoscopists participating in a regional colorectal cancer screening program based on colonoscopy after biennial fecal occult blood testing (FOBT)., Design: Two rounds of colonoscopy were performed: round 1 took place in 2003 and 2004, and round 2 took place in 2005 and 2006. Secondary analysis of colonoscopy findings from the first 2 rounds was performed by using data drawn from all endoscopists who performed more than 30 colonoscopies in each round. Detection rates were adjusted for patient age and sex, and logistic regression analyses were conducted including these 2 variables and round number (1 or 2)., Setting: District of Ille-et-Vilaine in Brittany (population >900,000) between 2003 and 2007., Main Outcome Measurements: The per-endoscopist adjusted rates of colonoscopies with at least 1, 2, or 3 adenomas, 1 adenoma 10 mm or larger, or a cancer., Results: Among the 18 endoscopists who performed 3462 colonoscopies, the adjusted detection rates were in the following ranges: at least 1 adenoma, 25.4% to 46.8%; 2 adenomas, 5.1% to 21.7%; 3 adenomas, 2.7% to 12.4%; 1 adenoma 10 mm or larger, 14.2% to 28.0%; and cancer, 6.3% to 16.4%. Multivariate analyses showed that the endoscopist was not an independent predictor of cancer detection, but was an independent predictor of detecting adenomas, regardless of category; the R(2) of the models ranged from 6% to 13% only., Limitations: Other factors known to influence colorectal neoplasia occurrence and withdrawal time could not be taken into account., Conclusions: In a screening program with a high compliance rate with colonoscopy after FOBT, interendoscopist variability had no effect on cancer detection, but did influence identification of adenomas. The clinical impact of such findings merits further evaluation.

Bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD) can produce emotional disorders that have been linked to disturbance of the STN's limbic territory. The aim of this study was to confirm the impairment of the recognition of facial emotions (RFE) induced by STN DBS, not only ruling out the effect of the disease's natural progression in relation to the effect of DBS, but also assessing the influence of modifications in dopamine replacement therapy (DRT) following STN DBS. RFE was investigated in 24 PD patients who underwent STN DBS and 20 PD patients treated with apomorphine. They were assessed 3 months before and after treatment. The 2 patient groups were compared with a group of 30 healthy matched controls. The results showed that RFE for negative emotions (fear and sadness) was impaired in only the STN DBS group in the posttreatment condition and was unrelated to DRT. Results confirm the selective reduction of RFE induced by STN DBS, due neither to the disease's natural progression nor to modifications in DRT., (Copyright 2009 APA, all rights reserved.)

To compare body mass index (BMI) and daily energy intake (DEI) after subthalamic versus pallidal deep brain stimulation (DBS). Weight gain following DBS in Parkinson's disease patients remains largely unexplained and no comparison of subthalamic and pallidal (GPi) stimulation has yet been performed. BMI and DEI, dopaminergic drug administration and motor scores were recorded in 46 patients with PD before STN (n = 32) or GPi (n = 14) DBS and 3 and 6 months after. At M6, BMI had increased by an average of 8.4% in the STN group and 3.2% in the GPi group. BMI increased in 28 STN and 9 GPi patients. This increase was significantly higher in the STN group (P < 0.048) and the difference remained significant after adjustment for reduced dopaminergic medication; 28.6% of GPi patients were overweight at 6 months (14.3% preoperatively) versus 37.5% of STN patients (21.9% preoperatively). Changes in BMI were negatively correlated with changes in dyskinesia in the GPi-DBS group. Food intake did not change in the two groups, either quantitatively or qualitatively. Frequent weight gain, inadequately explained by motor improvement or reduced dopaminergic drug dosage, occurred in subthalamic DBS patients. The difference between groups suggests additional factors in the STN group, such as homeostatic control center involvement., ((c) 2009 Movement Disorder Society.)

Object: In this article, the authors report their experience in the management of adult patients with medulloblastoma at their institution to identify prognostic factors important for survival and disease control., Methods: Between 1977 and 2005, 27 patients who were >or=16 years old and had medulloblastoma were treated consecutively. There were 16 women and 11 men with a median age of 21 years (range 16-54 years). Gross-total resection was performed in 21 patients, subtotal (>or=90%) in 2, incomplete in 1, and biopsy in 3 patients. Six patients had the desmoplastic variant, and 21 patients presented with classic medulloblastoma. Staging according to the Chang classification showed 4 patients with tumors invading the brainstem (2 with Stage T3b and 2 with Stage T4), 3 patients with metastases (2 with Stage M2 and 1 with Stage M3), and 1 patient in whom the stage was unknown (Stage MX) who died 10 days postoperatively. Twenty patients were assigned to the standard-risk group and 7 to the high-risk group. All patients except the one whose status was classified as Stage MX underwent craniospinal radiotherapy at our institution. Seven patients received chemotherapy before radiotherapy., Results: The 5- and 10-year overall survival rates for the present study were 81 and 62%, respectively. The median overall survival time was 17.7 years. The 5- and 10-year event-free survival rates were 72 and 57%, respectively. The median event-free survival time was 17.9 years. Univariate analysis showed that survival was significantly correlated with sex (women had a better prognosis than men) and M stage (patients without metastases had a better outcome). Patient age, duration of symptoms, Karnofsky Performance Scale score at presentation, hydrocephalus, tumor location, brainstem invasion, extent of resection, histological subtype, preradiotherapy chemotherapy, risk group, and period of presentation were not significant variables. Multivariate analysis identified sex and M stage as well as the period of presentation as independent prognostic factors for overall and event-free survival times. Eleven patients suffered tumor recurrence within a median time of 4.2 years. The posterior fossa was not the most common site of recurrence, and delayed recurrence was not rare. All patients in whom the tumor recurred have died despite aggressive treatments. The median survival time after diagnosis of recurrence was 2.5 years. Questionnaires on quality of life and cognition showed high scores in favor of limited negative effects in the perception of mental and physical health after treatment. The authors observed 1 supposed second malignancy (thyroid carcinoma) and no evidence of pituitary dysfunction., Conclusions: Long-term survival is possible in adults treated for medulloblastoma. Although rare, metastasis seeding at presentation is a poor prognostic factor. The possibility of delayed recurrence necessitates close follow-up of all patients. Tumor recurrences should be treated with aggressive therapies as some patients may have sustained response. Adjuvant chemotherapy should be given to high-risk patients, but its role in reducing recurrences, particularly distant ones, remains unclear in the standard-risk group.

The "orbitofrontal" and "cingulate" frontostriatal loops and the mesolimbic dopaminergic system that modulates their function have been implicated in theory of mind (ToM). Parkinson's disease (PD) provides a model for assessing their role in humans. Results of the handful of previous studies of ToM in PD providing preliminary evidence of impairment remain controversial, mainly because the patients included in these studies were not accurately described, making it difficult to determine whether their ToM deficits were due to general cognitive deterioration or to a more specific dopaminergic deficit. The aim of our study was therefore to re-examine previous results highlighting ToM in PD and to explore the involvement of the dopaminergic pathways in ToM. ToM was investigated in 17 newly diagnosed PD patients (early PD group), 27 PD patients in the advanced stages of the disease (advanced PD group) and 26 healthy matched controls (HC), using two ToM tasks: a visual one, which is thought to reflect the "affective" ToM subcomponent ("Reading the Mind in the Eyes"), and a verbal one, which is thought to reflect both the "affective" and the "cognitive" ToM subcomponents (faux pas recognition). Furthermore, the early PD group was studied in two conditions: with and without dopamine replacement therapy (DRT). We failed to find any significant difference in ToM between the early PD patients and the HC group. Furthermore, there was no difference between the early PD patients in the medicated and unmedicated conditions. Conversely, the advanced PD patients scored poorly on the intention attribution question ("cognitive" ToM score) in the faux pas recognition task. The present results suggest that the deficit in ToM only occurs in the more advanced stages of the disease. In addition, our results would appear to indicate that these advanced PD patients present "cognitive" ToM impairment rather than global ("cognitive" and "affective") ToM impairment. In other words, the ToM deficit would appear to be present in PD patients where the degenerative process has spread beyond the dopaminergic pathways, but not in early PD patients where neuronal loss is thought to be restricted to the nigrostriatal and mesolimbic dopaminergic systems. In conclusion, our results suggest that the dopaminergic pathways are not involved in ToM.

Most of the published works so far have aimed at finding genes associated with multiple sclerosis (MS) susceptibility. Very few studies have attempted to correlate disease features with DNA variants. In a well-characterized sample (651 patients) representative of multiple sclerosis natural history, we engaged a comprehensive study of the role of human leukocyte antigen (HLA) in the course of the disease. We investigated the role of HLA-DRB1*15 allele in samples stratified according to severity evaluated by the Multiple Sclerosis Severity Score (MSSS), time to reach EDSS 6.0 and disease type. We found that HLA-DRB1*15 genotype does not influence MS severity even among patients presenting with a given type of the disease. However, we show for the first time that HLA-DRB1*15 allele modulates the course of MS for relapsing-remitting (RR) onset patients likely by precipitating the secondary progressive (SP) phase.

Objective: To test the hypothesis that emotion recognition and apathy share the same functional circuit involving the subthalamic nucleus (STN)., Methods: A consecutive series of 17 patients with advanced Parkinson's disease (PD) was assessed 3 months before (M-3) and 3 months (M+3) after STN deep brain stimulation (DBS). Mean (+/-S.D.) age at surgery was 56.9 (8.7) years. Mean disease duration at surgery was 11.8 (2.6) years. Apathy was measured using the Apathy Evaluation Scale (AES) at both M-3 and M3. Patients were also assessed using a computerised paradigm of facial emotion recognition [Ekman, P., & Friesen, W. V. (1976). Pictures of facial affect. Palo Alto: Consulting Psychologist Press] before and after STN DBS. Prior to this, the Benton Facial Recognition Test was used to check that the ability to perceive faces was intact., Results: Apathy had significantly worsened at M3 (42.5+/-8.9, p=0.006) after STN-DBS, in relation to the preoperative assessment (37.2+/-5.5). There was also a significant reduction in recognition percentages for facial expressions of fear (43.1%+/-22.9 vs. 61.6%+/-21.4, p=0.022) and sadness (52.7%+/-19.1 vs. 67.6%+/-22.8, p=0.031) after STN DBS. However, the postoperative worsening of apathy and emotion recognition impairment were not correlated., Conclusions: Our results confirm that the STN is involved in both the apathy and emotion recognition networks. However, the absence of any correlation between apathy and emotion recognition impairment suggests that the worsening of apathy following surgery could not be explained by a lack of facial emotion recognition and that its behavioural and cognitive components should therefore also be taken into consideration.

Background: Mitoxantrone was approved by the French health authority (AFSAPPS) in October 2003 to treat patients with aggressive multiple sclerosis (MS)., Objective: To report the long term effectiveness and safety of mitoxantrone as induction therapy in patients with aggressive relapsing-remitting MS, and to assess treatment response factors., Material and Methods: 100 consecutive patients with aggressive relapsing-remitting MS received mitoxantrone 20 mg monthly combined with methylprednisolone 1 g for 6 months. Relapses, Expanded Disability Status Scale (EDSS) and drug safety were assessed every 6 months for up to at least 5 years. Within 6 months after induction, 73 patients received maintenance therapy (mitoxantrone every 3 months (n = 21); interferon beta (n = 25); azathioprine (n = 15); methotrexate (n = 7); glatiramer acetate (n = 5))., Results: During the 12 months following initiation of mitoxantrone, the annual relapse rate (ARR) was reduced by 91%, 78% of patients remained relapse free, MRI activity was reduced by 89%, the mean EDSS decreased by 1.2 points (p<10(-6)) and 64% of patients improved by 1 point or more on the EDSS. In the longer term, the ARR reduction was sustained (0.29-0.42 for up to 5 years), the median time to the first relapse was 2.8 years and disability remained improved after 5 years. Younger age and lower EDSS score at the start of mitoxantrone treatment were predictive of better treatment response. Three patients presented with an asymptomatic decrease in left ventricular ejection fraction to less than 50% (one reversible). One patient was diagnosed with acute myeloid leukaemia (remission 5 years after diagnosis)., Conclusion: Mitoxantrone monthly for 6 months as induction therapy followed by maintenance treatment showed sustained clinical benefit for up to 5 years with an acceptable adverse events profile in patients with aggressive relapsing-remitting MS.

Vascular endothelial growth factor (VEGF) is the major factor involved in angiogenesis. Although it is known that one of the functions of VEGF is to regulate neovascularization in renal cell carcinomas, the relationship between the production of VEGF in tumor tissue and its concentration in blood has not yet been studied. The aims of this study were to determine, in a series of conventional renal cell carcinoma (CRCC) cases, (1) VEGF expression and VEGF pattern in tumor cells, (2) the relationship between VEGF expression/pattern and VEGF levels in plasma (pVEGF), and (3) the association with usual clinical and pathologic prognostic factors. Fifty patients operated on for CRCC by radical nephrectomy were included. Clinical and histologic parameters were studied. VEGF expression and VEGF pattern in tumor cells was immunohistochemically recorded. pVEGF levels and platelet count were analyzed in relation to clinical and histologic parameters. Intratumoral VEGF expression associated with a cytoplasmic VEGF pattern was significantly higher in patients with high pVEGF levels (P = .01). Both VEGF expression and pVEGF levels were significantly correlated with Fuhrman grade (P = .002 and P = .01, respectively) and tumor stage (P = .006 and P = .008, respectively). In addition, VEGF expression was also correlated with tumor necrosis (P = .001) and progression (P = .001). We demonstrated that in CRCC with tumor necrosis, VEGF expression, pVEGF levels, and platelet count were significantly higher than in CRCC with no tumor necrosis (P = .001, P = .03, and P = .001, respectively). Our results revealed that cytoplasmic VEGF expression and pVEGF levels are associated with usual prognostic factors and progression in CRCC, which may allow VEGF to be used as a prognostic marker for CRCC, especially in patients with VEGF-targeted therapy.

In this preliminary study we analysed the impact of ovarian stimulations and the different protocols used for in vitro fertilizations (IVF) on the clinical activity of multiple sclerosis (MS). By matching the databases on MS and IVF of the past 10 years at the university hospital of Nantes, six patients have been found and, for five of them MS relapse rate seemed to be increased in the three-month period following IVF as compared to the previous three months and to two other control periods of three months (P<0.05, Friedman test). The increased relapse rate mainly concerned patients treated by GnRH agonists but not the patients treated by GnRH antagonists. This preliminary work suggests a possible impact of the treatments used for IVF on MS relapse rate. Further studies are now underway to validate these results on a larger scale, by including all cases reported in France.

In France no data have been published about comparing survival in multiple sclerosis (MS) patients with the general French population. We estimated survival probabilities in MS patients from a major centre for MS in West France. We also compared MS survival with the general population and assessed prognostic parameters. All patients with MS onset after January 1976 and classified as dead or alive on 1 January 2004 were included. One thousand eight-hundred and seventy-nine patients (sex ratio W: M 2.3; relapsing/progressive onset 77.4%/22.6%) fulfilled these criteria, disease duration ranged from one to 28 years. By 2004, 68 patients died (51 due to MS) and the 15 and 25-year survival probabilities were 96% and 88%. Male gender, progressive course (either primary or secondary), polysymptomatic onset, and increased annual relapse rate during the first two years of MS were related to a worse prognosis. After a mean follow-up duration of 12.7 years since clinical onset, MS increased the number of deaths compared with the general population. However taking into account disability status, we found that less disabled MS patients had a better survival and highly disabled patients a worse survival (eight-fold increase of mortality) compared with the French population.

Aims: The benefits of cardiac resynchronization therapy (CRT) on functional status, left ventricular (LV) remodelling and survival in patients with drug-refractory congestive heart failure (CHF), LV systolic dysfunction, and wide QRS have been demonstrated in randomized trials. However, the impact of CRT on right ventricular (RV) function, an independent prognostic factor in CHF remains questionable. This study examined the acute effects of various pacing modes on RV function in recipients of CRT systems., Methods and Results: Echocardiographic examinations were performed in 15 patients (median age: 67 years, range 49-78), to compare RV function during atrial (AAI), RV and LV pacing, and biventricular (BiV) pacing, in random order. At baseline, the median LV ejection fraction was 20% (range 10-35) and the median LV end-diastolic diameter was 78 mm (range 62-85). Right ventricular function was impaired, with a median 36% fractional shortening of RV surfaces (7-59). Tissue Doppler systolic peak of velocity (Sa) recorded at the tricuspid annulus increased significantly from 9.9 cm/s (range 4.7-16.5) during AAI pacing, 10 cm/s (range 5.4-20.3) during RV pacing, and 11.7 cm/s (range 4.6-16.7) during LV pacing to 12.6 cm/s (range 6.6-19.1) during BiV pacing (P < 0.01). Trends toward improvements in other indices of RV function, particularly myocardial performance index and systolic excursion of the tricuspid annulus, were also observed., Conclusions: This short-term study showed a significant improvement in RV systolic function during BiV pacing compared with AAI, RV, or LV pacing in CRT recipients.

Background: Invasive aspergillosis is an opportunistic infection that occurs mainly among patients with prolonged neutropenia. Few data are available on invasive aspergillosis in nonneutropenic patients., Methods: The aim of this survey was to compare neutropenic and nonneutropenic patients who had received a diagnosis of invasive aspergillosis at our institution during a 6-year period., Results: Among the 88 cases of invasive aspergillosis analyzed here, 12 were histologically proven, 52 were probable, and 24 were possible. Forty-seven percent of cases were diagnosed in the intensive care unit, and 40% were diagnosed in hematology units. Neutropenia was a risk factor for 52 patients (59%), most of whom had hematological or solid malignancies. Among the 36 nonneutropenic patients (41%), the main underlying conditions were steroid-treated chronic obstructive pulmonary disease, asthma, rheumatoid arthritis, giant-cell arteritis, and microvascular disorders; 10 patients were recipients of solid-organ transplants, and 1 patient was seropositive for human immunodeficiency virus. The distribution of proven and probable invasive aspergillosis was similar for neutropenic and nonneutropenic patients. The mortality rate was 71.5% overall and was significantly higher among nonneutropenic patients than among neutropenic patients (89% vs. 60%; P<.05). Compared with neutropenic patients, nonneutropenic patients were significantly less likely to have symptoms of invasive aspergillosis and more likely to have frequent intercurrent pneumonia due to another microorganism. The sensitivity of mycological examination of bronchoalveolar lavage fluid specimens was higher for nonneutropenic patients than for neutropenic patients (85% vs. 58%; P<.05), whereas the sensitivity of antigenemia was the same for the 2 populations (65% vs. 64%). Findings on thoracic computed tomographs were similar, except that segmental areas of consolidation occurred more frequently among neutropenic patients., Conclusion: This survey at a whole institution underlines the high number of cases of invasive aspergillosis among nonneutropenic patients, with an overall mortality rate that was significantly higher than that for neutropenic patients.

Purpose: We correlated platelet count to renal tumor characteristics, and evaluated the potential prognostic value of thrombocytosis in localized and metastatic tumors., Materials and Methods: A total of 804 patients operated on for a renal tumor in 2 French centers were included in this study. In all cases TNM stage, Fuhrman grade, tumor size, nodal invasion, ECOG score, histological subtype and platelet count were recorded. Survival estimates were compared with the Kaplan-Meier method and multivariate analysis was performed using a Cox model., Results: There were 538 (66.9%) males and 266 (33%) females (ratio 2.02) in the patient group. Median age was 62 years. T stages were T1, T2, T3 and T4 in 284 (35.3%), 116 (14.4%), 387 (48.1%) and 17 (2.1%), respectively. There were 112 (13.9%) and 126 (15.7%) patients with nodal and metastatic invasion, respectively. Platelet count was strongly correlated with T stage (p < 0.001), Fuhrman grade (p < 0.001), tumor size (p < 0.001), nodal invasion (p < 0.001) and the presence of distant metastasis (p = 0.01). In univariate analysis all studied factors were significantly predictive of survival (p = 0.0001). Thrombocytosis had an impact on prognosis in localized (p < 0.001) and metastatic (p = 0.003) disease. Several factors were retained in multivariate analysis, namely TNM stage, Fuhrman grade, tumor size, ECOG score and platelet count. In cases with a platelet count of less than 450,000/mm3, the 5-year survival rate was 70%, compared to 38% when the platelet count was 450,000/mm3 or greater., Conclusions: Platelet count appears to be an independent prognostic factor in renal cell carcinoma. It reflects a cascade of biological events correlated with tumor aggressiveness. This observation opens new perspectives for exploring carcinogenesis mechanisms and tumor progression in renal cell carcinoma.

Introduction: On the basis of the French and British (FB) MS Trial, Mitoxantrone (MITOX) was approved by the AFSAPPS in October 2003 in patients with aggressive multiple sclerosis (MS), given as induction therapy monthly for 6 months (ELSEP). We report an observational study of 100 aggressive relapsing remitting (RR) MS patients treated by induction therapy with MITOX and followed up to 5 years., Methods: One hundred patients with aggressive RR MS received an induction therapy with MITOX 20 mg monthly combined with methylprednisolone 1 g for 6 months. MRI data within 12 months before and 6 months after MITOX induction were collected (mean cumulative dose 65 mg/m2). Clinical evaluation was performed every 6 months and data (relapses and EDSS scores) were prospectively recorded in the EDMUS Database. After MITOX, a maintenance therapy was given to 57 patients (MITOX every 3 months: 21; Interferon beta: 13; Azathioprine: 14; Methotrexate: 7; Glatiramer acetate: 2). The mean follow-up period was of 3.8 years., Results: Patients were treated at a mean age of 27 +/- 9 years after 5 +/- 3 years of MS duration. Within the 12 months preceding MITOX onset, the annual relapse rate (ARR) was 3.2, the mean EDSS increased by 2.2 +/- 1 points (to a score of 4 at M0), 87 patients worsened by 1 point EDSS or more and 85 percent of patients had Gd enhancing lesions on MRI. During the 12 months following MITOX onset, the inflammatory activity of the disease dropped dramatically with a reduction of the ARR by 91 percent whereas 76 percent of patients were free of new relapse and MRI activity was reduced by 89 percent. In addition, the mean EDSS decreased by 1.2 points (p<10-6) and 60 percent of patients improved by 1 point EDSS or more. At a longer term, the reduction of the ARR was confirmed (0.28-0.37 up to 5 years) and the median time to the first relapse was 2.8 years. A significant improvement of disability was maintained until 4 years and got back to the initial level at year 5. The ARR was significantly lower (0.09) for patients treated with MITOX every 3 months as maintenance therapy than for patients treated by other disease modifying therapies (0.33-0.39) or not (0.43) after the induction. Three patients presented an asymptomatic decrease of the left ventricular ejection fraction under 50 percent, reversible in one case., Conclusion: MITOX as induction therapy monthly for 6 months was safe and had a rapid and strong impact on the inflammatory process and on the evolution of disability. The drug might be a good candidate as induction therapy followed by a maintenance therapy in patients with aggressive MS.

Hepatitis B virus-associated polyarteritis nodosa (HBV-PAN) is a typical form of classic PAN whose pathogenesis has been attributed to immune-complex deposition with antigen excess. We conducted the current study to 1) analyze the frequency of HBV infection in patients with PAN, in light of the classification systems described since 1990; 2) describe the clinical characteristics of HBV-PAN; 3) compare the evolution according to conventional or antiviral treatment; and 4) evaluate long-term outcome. One hundred fifteen patients were included in therapeutic trials organized by the French Vasculitis Study Group and/or referred to our department for HBV-PAN between 1972 and 2002. To determine the frequency of HBV-PAN during the 30-year period, we analyzed a control group of patients with PAN without HBV infection, followed during the same period and diagnosed on the same bases. Depending on the year of diagnosis, different treatments were prescribed. Before the antiviral strategy was established, some patients were given corticosteroids (CS) with or without cyclophosphamide (CY). Since 1983, treatment for patients with HBV markers has combined 2 weeks of CS followed by an antiviral agent (successively, vidarabine, interferon-alpha, and lamivudine) combined with plasma exchanges (PE).Ninety-three (80.9%) patients entered remission during this period and 9 (9.7%) of them relapsed; 41 (35.7%) patients died. For the 80 patients given the antiviral strategy as intention-to-treat, 4 (5%) relapsed and 24 (30%) died vs 5 (14.3%) relapses (not significant [NS]) and 17 (48.6%) deaths (NS) among the 35 patients treated with CS alone or with CY or PE. HBe-anti-HBe seroconversion rates for the 2 groups, respectively, were: 49.3% vs 14.7% (p < 0.001). Patients who seroconverted obtained complete remission and did not relapse.Thus, HBV-PAN, a typical form of classic PAN, can be characterized as follows: when renal involvement is present, so is renal vasculitis; glomerulonephritis due to vasculitis is never found; antineutrophil cytoplasmic antibodies (ANCA) are not detected; relapses are rare, and never occur once viral replication has stopped and seroconversion has been obtained. Combining an antiviral drug with PE facilitates seroconversion and prevents the development of long-term hepatic complications of HBV infection. The major cause of death is gastrointestinal tract involvement. Importantly, the frequency of HBV-PAN has decreased in relation to improved blood safety and vaccination campaigns.

Aims: Cardiac resynchronization therapy (CRT) is an effective treatment for refractory congestive heart failure (CHF). However, up to 30% of patients do not respond to CRT. The aim of this study was to identify clinical and electrocardiographic (ECG) predictors of a positive response to CRT., Methods and Results: This retrospective study included 139 consecutive patients successfully implanted with a CRT device (mean age, 68+/-9 years, 113 men). At baseline, 69% of patients were in New York Heart Association (NYHA) functional class III, and 31% in class IV, mean left ventricular ejection fraction was 21+/-6%, and mean QRS duration was 188+/-28 ms. In each patient, left and right ventricular leads were placed to attain the shortest QRS duration during biventricular stimulation. Patients were classified at 6 months as responders to CRT (n=100) if they were alive, they had not been re-hospitalized for management of CHF, and the NYHA class had decreased by 1 point, and/or peak VO(2) or 6 min hall-walk increased by >10%. All others were classified as non-responders (n=38; one patient was lost to follow-up). Uni- and multivariate logistic regression analyses were performed to detect a pre- or intra-operative predictor of a positive response to CRT. Among multiple demographic, clinical, and ECG variables, the amount of QRS shortening (DeltaQRS) associated with biventricular stimulation was the only independent predictor of a positive (37+/-23 ms) vs. negative (11+/-23 ms) response to CRT (P<0.001)., Conclusion: A positive response to CRT was observed in 73% of patients at 6 months and predicted only by DeltaQRS.

Background: The well known global improvement of quality of life (QoL) after bilateral high frequency chronic deep brain stimulation of the subthalamic nucleus (STN DBS) in Parkinson's disease (PD) is in contrast to behavioral disturbances as observed after surgery. Indeed the impact of DBS on physical versus mental aspects of QoL in PD remains unknown., Objective: To assess the influence of bilateral STN DBS on physical versus mental aspects of QoL in Parkinson's disease., Methods: The results of 27 patients for the Unified Parkinson's disease Rating Scale (UPDRS), Parkinson's Disease Questionnaire 39 (PDQ39) and Short Form 36 health survey questionnaire (SF36) were compared before surgery and after 12 months of bilateral STN DBS., Results: Comparing off-dopa conditions before versus 12 months after surgery, both UPDRS part II and part III significantly improved: 32.6% and 52%, respectively. UPDRS part I scores did not change significantly at 12 months. As for PDQ39, the global score significantly improved after surgery (21.1 %) as did four subscores: mobility (25.6 %), activity of daily living (34.5 %), stigma (40.1 %) and bodily discomfort (30 %). Three PDQ39 subscores, however, showed no significant changes: emotional well-being (10.7 %), social support (3.2%) and cognition (8.5 %) and one item even worsened: communication (-7.7 %). In SF36, only physical items significantly improved., Conclusion: Using clinician's based rating scale, bilateral STN DBS showed significant improvement in PD patients at 12 month follow up. However, using patient's self-assessment scales, the clinical benefit of STN DBS was more subtle: physical items of QoL significantly improved, whereas mental items such as emotional well-being, social support, cognition and communication showed no improvement. Our results are suggestive of a dissociation of motor and non-motor symptoms control after bilateral STN DBS in PD patients.

Cribriform and/or papillary prostatic lesions observed on limited tissue, such as needle biopsy, can pose diagnostic dilemmas. One such area of difficulty is the distinction between papillary and/or cribriform prostatic high-grade prostatic intraepithelial neoplasia (HG-PIN) and ductal adenocarcinoma. Over 48 months, we identified 17 cases of ductal adenocarcinoma and 17 cases of HG-PIN from radical retropubic prostatectomy specimens. The HG-PIN lesions were in all cases associated with an acinar prostatic adenocarcinoma component. For each case, we evaluated the proliferative activity, assessed by Ki-67 immunohistochemistry. The majority (82%) of ductal adenocarcinomas were composed of mixed papillary and cribriform patterns, with the remaining demonstrating pure papillary or cribriform patterns. The HG-PIN lesions showed a papillary, cribriform, or mixed papillary/cribriform architecture. The proliferative activity, defined as Ki-67 labeling index, was statistically higher in ductal adenocarcinoma (mean 33%, range 21%-66%) as compared with HG-PIN (mean 6%, range 2%-15%), with no overlap in the Ki-67 indices (P = 0001). A combination of histological features and measurements of cellular proliferation may be helpful to distinguish HG-PIN from ductal adenocarcinoma in limited prostatic tissue samples.

Purpose: To analyze to what extent histologic subtype is of prognostic importance in renal cell carcinoma based on a large, international, multicenter experience., Patients and Methods: Four thousand sixty-three patients from eight international centers were included in this retrospective study. Histologic subtype (1997 International Union Against Cancer [UICC] criteria of tumor response), age, sex, TNM stage, Fuhrman grade, tumor size, Eastern Cooperative Oncology Goup performance status (ECOG PS), and overall survival were determined in all cases. The prognostic values of clear cell, papillary, and chromophobe histologic features were assessed by uni- and multivariate analysis using the Kaplan-Meier method and Cox model, respectively., Results: Clear cell, papillary, and chromophobe carcinomas accounted for 3,564 (87.7%), 396 (9.7%) and 103 (2.5%) cases, respectively. In univariate analysis, a trend toward a better survival was observed when clear cell, papillary, and chromophobe histologies were considered prognostic categories (log-rank P = .0007). However, in multivariate analysis, TNM stage, Fuhrman grade and ECOG PS, but not histology, were retained as independent prognostic variables (P < .001)., Conclusion: The stratification in three main renal cell carcinoma histologic subtypes as defined by the 1997 UICC-American Joint Committee on Cancer consensus should not be considered a major prognostic variable comparable to TNM stage, Fuhrman grade and ECOG PS.

Purpose: We validate the prognostic value of a symptom based classification (S classification) in a multi-institutional study., Materials and Methods: A total of 2,242 patients from 5 European centers were included in this study. Based on symptoms at diagnosis, patients were stratified into 3 groups of S1-asymptomatic tumors, S2-tumors with local symptoms and S3-tumors with systemic symptoms. Variables such as age, gender, tumor size, TNM stage, Fuhrman grade, Eastern Cooperative Oncology Group (ECOG) performance status, perinephric fat, renal vein and adrenal invasion were also considered for prognostic value. The end point of the study was cancer specific survival. Survival assessment was made with univariate and multivariate analyses using the Kaplan-Meier method and Cox regression analysis., Results: Of the patients 1,018 (45.4%) were classified as S1, 865 (38.6%) S2 and 339 (16.0%) S3. The S classification correlated to tumor stage, grade and ECOG (p <0.001). On univariate analysis ECOG performance status, S classification, tumor size, TNM stage, Fuhrman grade, and adrenal, perinephric fat or vein invasion were significant prognostic factors (p <0.001). The S classification provided a significant prognostic stratification in the aggregate as well at each of the 5 centers. On multivariate analysis the S classification, TNM stage, Fuhrman grade, and perinephric fat and renal vein invasion remained independent prognostic factors (p <0.001)., Conclusions: This study confirms that it is possible to graduate symptoms for a prognostic purpose. The proposed symptom score should be evaluated for its integration in prognostic algorithms.

It has been reported in the literature that a leukemic cell may be (or become) resistant to anti-cancer treatment because many mechanisms, such as efflux membrane pump (multi-drug resistance, MDR-P170), intracellular transport (LRP, MRP), or different detoxification systems (glutathione transferases, methallothioneines) may be implicated. Topoisomerase II alpha (TopoII) are also reported as responsible for resistance since their main action is to repair DNA breakage. Polyamines are described as having a protective DNA action by stabilizing the double stranded DNA helix. For these reasons we investigated 65 children with acute lymphoblastic leukemia using an immunocytochemical method to elucidate the potential role of Topoisomerase and polyamines in drug resistance. Most children (60/65) were treated with the French (acute lymphoblastic leukemia, ALL) protocol (FRALLE-93) in which B and C arms include (at least) VP16. Children with cytoplasmic TopoII positivity (18 cases) were more resistant since their overall survival was 34 months compared to more than 110 months for negative cases ( P = 0.0003). Polyamines may be associated with drug resistance since the overall survivals were 51 months and 92 months for positive and negative patients, respectively, but the P-value is only 0.13. We conclude that Topoisomerase and polyamines must be tested at diagnosis as new possible markers for chemo-resistance. Larger series are needed to confirm these preliminary results and to verify if the use of anti epipodophillotoxin agents (as it is the case for FRALLE B or C) should be excluded for positive cases.

The failure to chemotherapy is a multi factorial phenomenon and lung resistance protein (LRP) overexpression has already been discussed as implicated in drug resistance. But its role is still discussed. In 1996, we studied the expression of LRP and P170 (MDR) in a series of leukemias, at the time of diagnosis, by immunocytochemical (ICC) method. The observation of a strong and unusual expression of LRP in acute myeloid leukemia (AML) with monocytic component led us to test (for P170 and LRP) a new series of 47 AML with different FAB subtypes. The expression of LRP was scored from 1 to 5 in blast cells and monocytes separately. We demonstrate that LRP is not correlated with clinical outcome but is statistically related to monoblastic leukemias. Code 5 reaction was found in 10/13 M5 versus the other FAB subtypes (P<10(-3)). The strongest LRP overexpression was also found in chronic myelomonocytic leukemia (four cases), reactive monocytosis (three cases) and in a dendritic cell line. In conclusion, we report that LRP is rather a marker of monocytic lineage than a prognostic index for MDR and we suggest that detection of LRP by ICC could be an argument for the diagnosis of monoblastic and monocytic leukemias.

Introduction: Studies have demonstrated the need for pain control during multiple transrectal prostate biopsies. Due to encountered published results on periprostatic nerve block, we prospectively evaluated the efficacy and safety of periprostatic local anaesthesia at the apex in comparison to intrarectal lidocaine gel., Methods: From January 2001 to January 2002 110 patients underwent prostate biopsy. Patients were randomized to receive 10 cc of either 2% lidocaine gel intrarectally (Group 1) or 10 cc of 1% lidocaine solution injected under ultrasound guidance for bilateral periprostatic nerve block at the apex (Group 2). Pain during biopsy was assessed using a 10-point linear visual analog pain scale and a 5-point digital visual pain scale (continuous variables). Statistical analysis of pain scores was performed using the Student t-test., Results: 96 patients fitted the inclusion and presented no exclusion criteria. 43 patients composed group 1, and 53 patients group 2. The mean pain score was 2.76+/-1.69 and 1.73+/-1.26 for group 1 and 2, respectively for the 10-point linear visual analog pain scale (p=0.001). The mean pain score was 2.26+/-0.82 and 1.62+/-0.56 for groups 1 and 2, respectively for the 5-point digital visual pain scale (p<0.001). There was no difference in mean patient age (p=0.348), prostate size (p=0.899), serum PSA (p=0.932), and complications when comparing both groups. The number of biopsies per patient was significantly higher in group 2 (p=0.006), but pain scores in each scale were significantly less., Conclusions: Periprostatic nerve block at the apex is superior to intrarectal lidocaine gel for controlling pain during transrectal prostate biopsy, with no increased complications. This technique should be recommended for those patients without anal or rectal inflammatory diseases.