Higher Number Of Relapses Research Articles

Post-natalizumab disease reactivation in multiple sclerosis: systematic review and meta-analysis

Background:Natalizumab (NTZ) is sometimes discontinued in patients with multiple sclerosis, mainly due to concerns about the risk of progressive multifocal leukoencephalopathy. However, NTZ interruption may result in recrudescence of disease activity.Objective:The objective of this study was to summarize the available evidence about NTZ discontinuation and to identify which patients will experience post-NTZ disease reactivation through meta-analysis of existing literature data.Methods:PubMed was searched for articles reporting the effects of NTZ withdrawal in adult patients (⩾18 years) with relapsing–remitting multiple sclerosis (RRMS). Definition of disease activity following NTZ discontinuation, proportion of patients who experienced post-NTZ disease reactivation, and timing to NTZ discontinuation to disease reactivation were systematically reviewed. A generic inverse variance with random effect was used to calculate the weighted effect of patients’ clinical characteristics on the risk of post-NTZ disease reactivation, defined as the occurrence of at least one relapse.Results:The original search identified 205 publications. Thirty-five articles were included in the systematic review. We found a high level of heterogeneity across studies in terms of sample size (10 to 1866 patients), baseline patient characteristics, follow up (1–24 months), outcome measures (clinical and/or radiological), and definition of post-NTZ disease reactivation or rebound. Clinical relapses were observed in 9–80% of patients and peaked at 4–7 months, whereas radiological disease activity was observed in 7–87% of patients starting at 6 weeks following NTZ discontinuation. The meta-analysis of six articles, yielding a total of 1183 patients, revealed that younger age, higher number of relapses and gadolinium-enhanced lesions before treatment start, and fewer NTZ infusions were associated with increased risk for post-NTZ disease reactivation (p ⩽ 0.05).Conclusions:Results from the present review and meta-analysis can help to profile patients who are at greater risk of post-NTZ disease reactivation. However, potential reporting bias and variability in selected studies should be taken into account when interpreting our data.

Intermittent Imatinib Mesylate in Children with Chronic Myeloid Leukemia: Results and Outcome

Intermittent Imatinib Mesylate in Children with Chronic Myeloid Leukemia: Results and Outcome

Rituximab does not Prevent Focal and Segmental Glomerulosclerosis Recurrence after Renal Transplantation in Patients at Risk

SENTRA-GLOSEN. Introduction Recurrence of focal and segmental glomerulosclerosis (FSGS) after renal transplantation is a characteristic complication of the disease that occurs in one third of the cases and has an important detrimental influence on graft survival. Different characteristics have been proposed as risk factors for recurrent disease although there is no general agreement on their importance and significance. Some studies have suggested that rituximab, administered at the time of transplantation, may be effective in preventing recurrence, but such efficacy has not been corroborated. Materials and Methods We perform a multicenter retrospective cohort study including 93 kidney transplants between years 2000 and 2014 in 87 patients [6 patients received a second transplant] with biopsy-proven FSGS as the underlying primary disease; patients with genetic or secondary causes were excluded. The aims of the study are to identify those factors that predict proteinuria recurrence and to analyze the efficacy of rituximab as preventive treatment in patients at risk. We also evaluate remission after recurrence treatment and the impact of recurrence on the graft survival. Results Fifteen patients (16.1%) presented a FSGS recurrence. When the analysis was restricted to those patients presenting with nephrotic syndrome at baseline, the incidence of recurrence increased to 44.1%. A younger age at diagnosis, a lower serum albumin and higher amount of proteinuria at baseline, more frequent immunosuppressive treatments at baseline, a higher number of relapses in previous transplants and a lower age at the time of transplantation were associated with the risk of recurrence. By multivariate analysis, the only risk factor for FSGS recurrence was the value of serum albumin at baseline. RTX (1g at induction and 1g two weeks after transplantation) was used as a potential prophylactic treatment in 12 of the 34 patients considered at risk for FSGS recurrence (hypoalbuminemia and nephrotic proteinuria at baseline). Clinical and analytical characteristics, both at baseline and at transplantation, were similar in both groups. No differences were found in the number of recurrences: 6/12 (50%) among RXT-treated patients and 9/22 (40.9%) versus non-treated patients (p = 0.610). Proteinuria remission after different treatments, most of them including plasmapheresis, was observed in 71.4% of patients. The addition of RTX to plasmapheresis did not increase efficacy. FSGS recurrence had a remarkable impact on graft survival, with 53% functioning grafts at the end of follow-up among patients who had suffered recurrence versus 88,5% in those who did not (p = 0.004); graft survival of FSGS recurrent patients achieving proteinuria remission after treatment was similar to that of patients without recurrence. Discussion In conclusion, the presence of hypoalbuminemia at the onset of the disease is the main predicting factor for FSGS recurrence. Rituximab does not prevent FSGS recurrence in patients at risk.

Superiority of Buprenorphine over Suboxone in Preventing Addiction Relapse in Opioid Addicts under Maintenance Therapy: A Double-Blind Clinical Trial

Background: In maintenance therapy for opioid addiction, to reduce the risk of buprenorphine (BUP) abuse, the combination of BUP and naloxone (NX) has been developed and is commercially available as suboxone (BUP/NX). This study was designed to compare addiction relapse frequency in patients receiving BUP and BUP/NX as maintenance therapy. Methods: In this double-blind clinical trial with cross over design, 100 opioid abusers were randomly assigned to two treatment groups to receive either BUP or BUP/NX. After three months, without a time-out period, subjects undertook treatment with the other drug. The subjects were screened weekly for urinary morphine. Results: In each of the study arms, when the patients were given BUP/NX, the number of relapses was significantly higher compared to when they received BUP (0.13±0.24 vs. 0.04±0.09, P = 0.001). If participants� age was taken into account, the number of relapses was significantly higher when BUP/NX was given in age groups of 31 to 40 years and over 50 years (P < 0.05). The length of addiction had also a significant impact on the number of relapses, i.e., patients with over 10-year history of addiction had higher number of relapses if they were given BUP/NX compared with BUP (P < 0.05). Conclusion:BUP seems to be more effective than BUP/NX in preventing addiction relapse in opioid abusers under maintenance treatment.

Predictors of frequent relapsing and steroid-dependent nephrotic syndrome in children.

To determine the predictors of frequent relapses and steroid dependency in children with steroid-sensitive nephrotic syndrome. All children aged six months to 18 years with steroid-sensitive nephrotic syndrome registered in the nephrology clinic between 2003 and 2015 at a tertiary center who were followed up for at least 1year after onset were included in the study. Two hundred seventy-seven patients with steroid-sensitive nephrotic syndrome who were followed up for at least 1 year from onset of disease were included. There were 157 infrequent relapsers and 120 frequent relapsers (frequent relapses and or steroid-dependent). Compared with infrequent relapsers, frequent relapsers had a significantly lower age at onset (51.53±40.42 vs. 61.97±40.66 months; p=0.035), lesser time for first relapse (time from the start of initial treatment to first relapse (8.65±11.99 vs. 23.46±24.05 months; p<0.001) and a higher number of relapses with infection (8.65±11.99 vs. 1.25±1.85; p<0.001). On multivariate logistic regression analysis, time for first relapse less than six months [OR: 3.93; 95% CI: (1.97-7.82)] and concomitant infection during relapses [OR: 1.82; 95% CI:(1.56-2.14)] were significant predictors of frequent relapses, and males were less likely to become frequent relapsers [OR: 0.48; 95% CI:(0.24-0.93)]. Kaplan-Meier analysis and the log-rank test also showed that a first relapse within six months was associated with frequent relapses. Age at onset and inadequate steroid therapy at onset did not determine frequent relapses. Shorter time for first relapse and concomitant infection during relapses can predict future frequent relapses. These predictors may be useful to counsel patients, to follow them up more closely, and to develop better treatment protocols and relapse-specific interventions.

Clinical Utility of the Predominant Polarity in Bipolar Disorder Patients

Introduction: Current classification of bipolar disorder (BD) in type I or type II may be of little use in routine clinical practice to provide information on relevance epidemiological and clinical variables. New complementary coders like the predominant polarity (PP), which is defined as a clear tendency in the patient to present relapses in the manic polarity predominance (MPP) or in the depressive polarity predominance (DPP) along the disease may be important to develop clinical and pharmacological strategies to prevent any kind of relapse. Objectives: To define the concept of PP and the epidemiological and clinical variables associated with the PP in order to know the clinical implications of that specific diagnosis factor. Methods: We realized a systematic review in the principal medical databases (until June 2016) including key words as “bipolar disorder”, “polarity and “predominant polarity”. Results: After apply the inclusion criteria we analysed 16 articles. The MPP was associated with manic onset of illness, history of substance abuse before the beginning of the disease and with a better response to atypical antipsychotics and mood stabilizers. Meanwhile the DPP is related with a depressive onset of the disease, a higher number of relapses, longer acute episodes, and a higher risk of suicide. Also, the delay until the correct diagnosis, the presence of mixed states and the comorbidity with anxiety disorders are more frequents in DPP that shows an increased use of quetiapine and lamotrigine. Conclusion: PP may be useful in the clinical management of BD. Further studies on biological and clinical factors are needed, with a common definition and a unified methodology

Correlation of clinical findings and brain volume data in multiple sclerosis

Brain volume measurements are becoming an important tool for assessing success in controlling multiple sclerosis (MS) activity. MSmetrix (icometrix) is an easy-to-use platform, specific for MS magnetic resonance imaging (MRI) of the brain. It provides data on total brain volume, grey matter volume and lesion load volume. The objective of the present study was to assess whether disability and the number of relapses during the previous year correlated with brain volume measurements from MSmetrix. Data on 185 icometrix reports from patients with MS were used to evaluate the potential correlation between brain volume measurements and clinical parameters. There was a significant correlation between higher disability and decreased brain volume (total and grey matter). Increased lesion load in the brain and higher number of relapses in the previous year were also independently correlated with decreased brain tissue volume and with increased disability. This is the first study with real-world data to show that icometrix is a relevant tool for the study of brain volume loss in MS.

Major psychotrauma and social stress–risk factors for the unfavorable course of paranoid schizophrenia

IntroductionRecent studies in the neurobiology of schizophrenia highlighted the role of neuropsychoendocrine activations as a consequence of psychostress followed by the activation of the HPA axis with an excess of endogenous cortisol. The relation endogenous cortisol–glutamatergic hyperactivation enhances the excito-toxic mechanisms and the cortical-subcortical alterations in schizophrenia.MethodWe conducted a retrospective study on 40 patients, with ages between 25 and 55 years, admitted in the university clinic of Craiova between January 1, 2015 and December 31, 2015 for paranoid schizophrenia according to ICD-10 criteria and with positive history of psychotrauma and physical abuse in childhood and adolescence.ResultsThe frequency of psychotraumas, social stress and physical abuse in our group was significantly higher in women (63.33%), in patients with urban residence (80.00%) and age group 36–45 years (46.67). There was a pattern of residual defectuality reflected by positive symptoms (83.33%), alcohol abuse (80.00%), aggressive behavior (66.67%) and suicide attempts (30.00%). The poor course with minimal social functioning (GAFS &lt; 40; 36.67%) was correlated with a high number of relapses and hospitalizations (&gt; 9 hospitalizations; 43.33%), cognitive deficit (MMSE &lt; 23; 76.67%). The psychosocial factors involved in the pathogenesis and course of schizophrenia were social stress (60.00%), physical abuse in childhood and adolescence (20.00%) and psychotraumas (20.00%).Conclusions.Psychotrauma and physical abuse in childhood and adolescence and during the course of paranoid schizophrenia constitute a risk factor for a poor outcome with cognitive deterioration, aggressive and suicidal behavior that call for prophylactic measures and qualified psycho-social interventions associated to the pharmacological treatments.Disclosure of interestThe authors have not supplied their declaration of competing interest.

The Second Antithyroid Drug Treatment Is Effective in Relapsed Graves' Disease Patients: A Median 11-Year Follow-Up Study.

Antithyroid drug (ATD) is a widely used treatment for Graves' disease (GD). However, its long-term efficiency remains unclear. This study investigated the long-term disease prognosis and predictive factors for relapse in ATD-treated GD patients. Newly diagnosed, ATD-treated GD patients with at least four years of follow-up were recruited (n = 187). Remission was defined as maintaining a euthyroid status for more than one year after ATD withdrawal. During 11.1 years (range 4.0-23.7 years) of median follow-up, overall, 51.9% of the newly diagnosed ATD-treated GD patients achieved remission, 32.1% continued ATD treatment, and 13.4% underwent other ablation treatments. The 10-year remission rates were higher in the first (34.2%) and second (25.5%) ATD courses than in any of the other subsequent ATD courses, and decreased as ATD treatments were repeated. The 10-year relapse rate was the highest after the third ATD treatment (71.4%) compared with that after the first (60.5%) and second (58.3%) courses. Longer duration of ATD treatment (odds ratio [OR] = 1.4 [confidence interval (CI) 1.2-1.7], p < 0.001), higher number of relapses (OR = 4.7 [CI 2.3-9.8], p < 0.001), and moderate to severe Graves' ophthalmopathy (OR = 4.1 [CI 1.1-15.2], p = 0.032) were associated with persistent disease status. A second course of ATD can be considered for GD patients after the first relapse because the chance of remission and the relapse rate are similar to the one after the first ATD treatment course. For GD patients with more than two relapses, or with an ATD treatment duration of more than four to five years, low-dose maintenance of ATD or ablative treatment needs to be considered.

No evidence for an effect on brain atrophy rate of atorvastatin add-on to interferon β1b therapy in relapsing–remitting multiple sclerosis (the ARIANNA study)

Background: A previous phase 2 trial has suggested that statins might delay brain atrophy in secondary progressive multiple sclerosis. Objectives: The objective of this study was to evaluate the effect of atorvastatin add-on therapy on cerebral atrophy in relapsing–remitting multiple sclerosis. Methods: This randomised, placebo-controlled study compared atorvastatin 40 mg or placebo add-on therapy to interferon β1b for 24 months. Brain magnetic resonance imaging, multiple sclerosis functional composite score, Rao neuropsychological battery and expanded disability status scale were evaluated over 24 months. Results: A total of 154 patients were randomly assigned, 75 in the atorvastatin and 79 in the placebo arms, with a comparable drop-out rate (overall 23.4%). Brain atrophy over 2 years was not different in the two arms (−0.38% and −0.32% for the atorvastatin and placebo groups, respectively). Relapse rate, expanded disability status scale, multiple sclerosis functional composite score or cognitive changes were not different in the two arms. Patients withdrawing from the study had a higher number of relapses in the previous 2 years (P=0.04) and a greater probability of relapsing within 12 months. Conclusions: Our results suggest that the combination of atorvastatin and interferon β1b is not justified in early relapsing–remitting multiple sclerosis and adds to the body of evidence indicating an absence of significant radiological and clinical benefit of statins in relapsing–remitting multiple sclerosis.

Natalizumab Discontinuation and Treatment Strategies in Patients with Multiple Sclerosis (MS): A Retrospective Study from Two Italian MS Centers.

IntroductionNatalizumab (NTZ) discontinuation can be followed by multiple sclerosis (MS) disease reactivation. Currently no disease-modifying drug (DMD) has been shown to be able to abolish disease reactivation. The aims of the current study were: (1) to determine the frequency of MS reactivation after NTZ discontinuation; (2) to evaluate predictors of reactivation risk, and (3) to compare the effect of different treatments in reducing this risk.MethodsData from 132 patients with MS followed-up for 2 years before NTZ treatment and 1 year after interruption were collected from two Italian MS centers and retrospectively evaluated.ResultsOverall, 72 of 132 patients (54.5%) had relapses after NTZ discontinuation and 60 of 125 patients (48%), who had magnetic resonance imaging, had radiological reactivation. Rebound was observed in 28 of 132 patients (21.2%). A higher number of relapses in the 2 years before NTZ treatment, a longer washout period, and a lower number NTZ infusions correlated with reactivation and rebound. Untreated patients (n = 37) had higher clinical and radiological activity and rebound in comparison to patients receiving DMDs. Moreover, a lower risk of relapses was found in patients treated with second-line therapies (NTZ and fingolimod) than in those treated with first-line therapies (interferon beta, glatiramer acetate, teriflunomide, azathioprine). Interestingly, no disease reactivation in off-label treatment (rituximab, autologous hematopoietic stem cell transplantation) was observed.ConclusionNTZ discontinuation is a risk for MS reactivation and rebound. An alternative treatment should be promptly resumed mainly in patients with a previous very active disease course and with a shorter NTZ therapy. Second-line therapies demonstrate superiority in preventing relapses after NTZ discontinuation.Electronic supplementary materialThe online version of this article (doi:10.1007/s40120-015-0038-9) contains supplementary material, which is available to authorized users.

Predictors of disease activity in 857 patients with MS treated with interferon beta-1b.

Multiple sclerosis (MS) is a chronic demyelinating neurodegenerative disease of the CNS that requires long-term treatment. The identification of patient characteristics that can help predict disease outcomes could improve care for patients with MS. The objective of this study is to identify predictors of disease activity in patients from the BEYOND trial. This regression analysis of patients with relapsing–remitting MS from BEYOND examined the predictive value of patient characteristics at baseline and after 1 year of treatment with interferon beta-1b 250 μg every other day for clinical and MRI outcomes after year 1 of the study. 857 and 765 patients were included in the analyses of clinical and MRI outcomes, respectively. In multivariate analyses of age, a higher number of relapses in the past 2 years, ≥3 new MRI lesions in the first year, and, especially, a higher number of relapses in year 1 predicted the future occurrence of relapses. By contrast, age, MRI activity, and the presence of neutralizing antibodies in the first year were principally predictive of future MRI activity. In patients with continued clinical disease activity or substantial MRI activity on therapy, an alternative therapeutic approach should be strongly considered.

Subclinical central inflammation is risk for RIS and CIS conversion to MS

Background: Subtle diffuse intrathecal inflammation is undetectable by conventional neuroimaging, and could influence multiple sclerosis (MS) disease course. Objective: To explore the role of subclinical persisting intrathecal inflammation in radiologically isolated syndrome (RIS) or clinically isolated syndrome (CIS) conversion to MS, and in early MS disease reactivation. Methods: One-hundred ninety-three subjects with RIS, CIS, relapsing–remitting (RR), or primary progressive (PP) MS were included, along with 76 matched controls. Cerebrospinal fluid (CSF) levels of interleukin-8 (IL-8), a major proinflammatory cytokine, were measured as a biomarker of intrathecal inflammation. Patients were followed up for 2 years. Clinical and imaging measures of disease progression were recorded. Results: High central contents of IL-8 were associated to clinical progression in subjects with RIS, and to the risk of conversion to MS in subjects with CIS. Asymptomatic intrathecal inflammation placed subjects at risk for MS conversion, even regardless lesion load. CSF IL-8 levels were higher in RR MS with high disease activity. Higher number of relapses in the first two years since diagnosis and shorter first inter-attack intervals were observed in patients with high levels of IL-8. Conclusion: IL-8 might provide utility in determining the presence of active intrathecal inflammation, and could be important in diagnostically undefined cases.

Cumplimiento de las guías de la Sociedad Española de Neurología en el tratamiento de los pacientes con esclerosis múltiple

Treatment of multiple sclerosis is based on the administration of the disease modifying drugs (DMD), used to slow the natural course of the disease. To assess the degree of compliance of Spanish neurologists with 2010 Spanish Neurology Society (SEN) treatment guidelines. Observational, retrospective and multicenter study of 218 adult patients with at least five years of disease evolution and under treatment with DMD. Data on their past/current management was obtained from their medical records and descriptively compared to SEN recommendations. According to SEN 2010 guidelines, 82% of patients had an adequate clinical response and 18% had an inadequate clinical response to their current DMD; 94% and 92%, respectively, maintained that treatment. Patients in which inadequate clinical response did not motivate a change in the current DMD more frequently had higher disability decline and higher number of relapses during previous treatments, and longer treatment duration with their current DMD. Regarding the sequence of DMDs used, 48% of patients initiated first-line treatment with interferon beta-1a administered through subcutaneous (29%) or intramuscular injections (19%), followed by interferon beta-1b, and glatiramer acetate. Some patients received second-line treatments as second/third option (15% and 28% respectively), but these treatments (mostly natalizumab) were only widespread from fourth treatment onwards. In accordance with SEN 2010 guidelines, the majority of patients from the study had an adequate clinical response. A high percentage of patients with an inadequate clinical response remained with their current treatment. An explanation to this phenomenon could be found in the chronic, complex and variable nature of multiple sclerosis.

MS in Maghrebian inhabitants and immigrants

Genetic predisposition, unknown environmental factors, or a combination of both may explain the variable prevalence of multiple sclerosis (MS) in the world. Few epidemiological data are available concerning MS patients in Maghreb. Studies of Maghrebian immigrants showed a more aggressive course of MS in Maghrebian population than in European patients. The prevalence of MS in the Maghreb was found to increase over the past few decades. Thus, Maghrebian population moved from a low prevalence area to a medium prevalence zone. An increase of female incidence of MS patients in the Maghreb was reported. MS in Maghrebian immigrants was well studied and results showed a more aggressive course in comparison to European population with mostly primary progressive forms and cerebellar symptoms. Despite an earlier onset in Maghrebian immigrants patients, the disease progresses more rapidly, with a higher proportion showing incomplete recovery from the first relapse, a shorter time between the first two relapses, a higher number of relapses in the first 5 years, and a shorter time to reach an EDSS of 4 and 6. Clinical course in Maghrebian population varies among recent studies. Some studies showed an aggressive course but not in others. However, in our experience through a multicentre Maghrebian study, MS patients have quite similar clinical feature and disability progression to European patients. Factors contributing to this variation include different methodology, short follow up period and lack of prospective studies. Prospective multicentre studies in Maghrebian population will better characterize the clinical course in the Maghreb.

Neuroimagerie de l’insight dans la schizophrénie : revue de la littérature

ObjectivesInsight in psychiatry has been defined and conceptualized in a number of ways but none of them was found to be self-explanatory. There has been an exponential rise in studies of insight, in part accelerated by the availability of several psychometric scales for measuring insight. Lack of insight has been associated in schizophrenia with low treatment adherence, a high number of relapses, increased number of hospital admissions, and subsequently poorer psychological and cognitive functioning. For this reason, there is considerable interest in understanding the underlying neural mechanisms of insight, which may have important implications for the development of future insight-oriented neuro-psychiatric treatment. Neuroimaging may be considered an important technique to help understand the anatomical, functional and metabolic neurocircuitry underlying poor insight in schizophrenia. Growing neuroimaging research provides evidence for underlying brain impairment in insight deficits in schizophrenia. In order to expose a panoramic view to the readers, this article reviews the neuroimaging studies conducted to date, which have investigated the neural bases of insight in schizophrenia. MethodsElectronic searches were performed in PubMed, PsycINFO, Sciencedirect and Web of Science databases, using the following keywords: Imaging; neuroimaging; Positron Emission Tomography (PET); spectroscopy; functional Magnetic Resonance Imaging (fMRI); structural Magnetic Resonance Imaging (MRI); Single Photon Emission Computed Tomography (SPECT); Voxel Based Morphometry (VBM); Diffusion Tensor Imaging (DTI); Computed Tomography (CT); Insight; schizophrenia; awareness of illness. Searches were also performed from the references of the systematic review articles on neurobiological correlates of insight in schizophrenia. Animal studies and single case reports were excluded. Twenty-five articles were selected for the present review. From these; 12 used structural MRI; 6 used VBM; 3 used fMRI; 2 used CT; 1 used DTI and 1 used VBM combined to DTI. ResultsThe search showed that studies in this area were published recently and that the neuroanatomic substrate of insight in schizophrenia has not yet been consolidated. This inconsistency could arise from the complex nature of insight and the use of a variety of insight assessments. Most of the studies analyzed in this review used structural neuroimaging techniques to assess brain abnormalities associated with poor insight. The functional neuroanatomy of insight has only recently been investigated and to our knowledge, there are only 3 studies that have examined brain activity with fMRI in relation to insight in schizophrenia. ConclusionThis review investigated the neural deficiencies underlying poor insight in schizophrenic patients. In spite of methodological differences among studies, results provide evidence of structural and functional brain abnormalities in frontal, parietal and temporal region related to insight deficits. Some studies have found a hemispheric asymmetry in relationship to poor in insight (the majority of brain abnormalities concern the right hemisphere). In addition, growing research indicated that the prefrontal cortex, particularly the dorsolateral prefrontal cortex, the anterior cingulated cortex, the insula, the precuneus and the cerebellum can also underlying insight in schizophrenia. It is interesting to mention that some authors have suggested that each dimension of insight can be specifically linked to certain brain structures. Taking together, data on the neuropsychological and neuroanatomical correlates of clinical insight suggested that lack of insight in schizophrenia could be conceived as a neurocognitive deficit, analogously to anosognosia in brain injury and dementia. On the contrary, to date, the neuroanatomical correlates of cognitive insight have been scarcely studied. Only two studies reported that Self-reflectiveness was positively related to gray matter volume of the right ventro-lateral prefrontal cortex, the BCIS composite index was positively correlated with total left hippocampal volume, and Self-certainty was inversely correlated with bilateral hippocampal volumes. However, it is important to note that neuroimaging research on cognitive insight in schizophrenia is in a preliminary, and the results on this are inconclusive. Further research is needed to better understand the causal relationships between brain abnormalities and degradation of insight in schizophrenia.

Postpartum relapses increase the risk of disability progression in multiple sclerosis: the role of disease modifying drugs

ObjectiveTo assess relapses, disability progression and the role of disease modifying drugs (DMDs) in the year after delivery in women with multiple sclerosis (MS).MethodsWe prospectively followed-up pregnancies occurring between 2002...

EPA-1537 - Clinical predictors of non-response in 253 patients with treatment resistant-depression

Introduction Treatment Resistant-Depression (TRD), known as the failure to respond to at least two different adequate trials of antidepressant treatments (ADT) in the current episode, is a relatively frequent clinical condition, associated to a high number of relapses, hospitalizations, and an elevated use of multiple pharmacological treatments. To date, however, the association between clinical variables and non-response in TRD remains unclear. Objectives To identify predictors of non-response in inpatients with Major Depressive Disorder (MDD) and TRD. Aims To investigate clinical variables as potential predictors of non-response in TRD. Methods Two hundred fifty-three inpatients with MDD and TRD were divided into two groups: responders and non-responders to drug therapies, according to a decrease of 50% or more of the severity of depression (measured with HAM-D 17 items) at the end of forth week of hospitalization. A general model of Cox regression (with backward stepwise method) was used to identify independent predictors of non-response to treatment. Results One hundred fifty-four TRD inpatients were responders and 99 non-responders. Cox regression identified three independent clinical predictors independently associated with the group of non-responders: (1) the presence of 5 or more depressive episodes in the medical history (OR = 2.27); (2) a current comorbid anxiety disorder (OR = 1.85); (3) a history of early life adversities (ELAs) (OR = 1.60). Conclusions The findings of this study suggest that the phenomenon of non-pharmacological response in the TRD is associated with different clinical variables, which might act through separate mechanisms in determining the persistence of depressive symptomatology.

P673 ATG16L1 and IRGM1 polymorphisms in pediatric Crohn's disease: correlation with phenotype

Background: Genome wide association studies (GWAS) find a significative correlation between several single nucleotide polymorphisms (SNPs) involved in autophagy and the occurrence of Crohn’s disease (CD) risk both in children and in adult patients. However, few incomplete and discordant evidences about the correlation of these SPNs and a specific phenotype of CD have been described in pediatric patients. Our purpose is to investigate the relationship between the autophagy gene variants of ATG16L1 and IRGM1 and clinical features in our cohort of children affected by CD. Methods: Eighty consecutive children with CD (mean age: 14.8±4.6 years) were enrolled in our study. Genotyping for ATG16L1 (rs2241880) and IRGM1 (rs13361189; rs4958847) was performed in all patients. Phenotypic informations including disease localization and behaviour stratified according to the Paris classification were collected. Moreover, phenotype data regarding medical therapy, relapses, surgery recurrences and laboratoristic inflammation parameters were analysed. Results: CD patients with the homozygous variant for the ATG16L1 (var) allele showed a significant tendence to change the clinical behaviour switching to a stenosing or fistolizing phenotype during the course of disease compared with children carrying the homozygous protective allele of ATG16L1 (wt) and heterozygous patients (het) (p = 0.05). In addition, the presence of ATG16L1 var resulted to be associated with a major recurrence of clinical relapses and an earlier introduction of immunosuppressants (p = 0.006 and p = 0.04 respectively). However, ATG16L1 var seems not to be related to a positive family history and extraintestinal manifestations (p = 0.4 and p = 0.5) and resulted to be protective for perianal disease, which was more frequent in het and wt patients (p = 0.06). Patients carrying ATG16L1 var were more frequently males (p = 0.07) and presented a signifcant higher value of fecal calprotectin at diagnosis (p = 0.007). IRGM1 rs4958847 homozygous variant was correlated with a trend toward statistical significance regards to a positive family history (p = 0.078) and the presence of extraintestinal manifestations (p = 0.08). Conclusions: CD patients carrying ATG16L1 var seem to be characterized by a more aggressive disease course, including changes in clinical behaviour, a higher number of relapses and an earlier use of immunosuppressants. IRGM1 rs4958847 variant gene is correlated with a positive family history and with extraintestinal manifestations.

P674 Pancreatitis associated to inflammatory bowel disease (IBD): clinical and genetic patterns in children

Background: Genome wide association studies (GWAS) find a significative correlation between several single nucleotide polymorphisms (SNPs) involved in autophagy and the occurrence of Crohn’s disease (CD) risk both in children and in adult patients. However, few incomplete and discordant evidences about the correlation of these SPNs and a specific phenotype of CD have been described in pediatric patients. Our purpose is to investigate the relationship between the autophagy gene variants of ATG16L1 and IRGM1 and clinical features in our cohort of children affected by CD. Methods: Eighty consecutive children with CD (mean age: 14.8±4.6 years) were enrolled in our study. Genotyping for ATG16L1 (rs2241880) and IRGM1 (rs13361189; rs4958847) was performed in all patients. Phenotypic informations including disease localization and behaviour stratified according to the Paris classification were collected. Moreover, phenotype data regarding medical therapy, relapses, surgery recurrences and laboratoristic inflammation parameters were analysed. Results: CD patients with the homozygous variant for the ATG16L1 (var) allele showed a significant tendence to change the clinical behaviour switching to a stenosing or fistolizing phenotype during the course of disease compared with children carrying the homozygous protective allele of ATG16L1 (wt) and heterozygous patients (het) (p = 0.05). In addition, the presence of ATG16L1 var resulted to be associated with a major recurrence of clinical relapses and an earlier introduction of immunosuppressants (p = 0.006 and p = 0.04 respectively). However, ATG16L1 var seems not to be related to a positive family history and extraintestinal manifestations (p = 0.4 and p = 0.5) and resulted to be protective for perianal disease, which was more frequent in het and wt patients (p = 0.06). Patients carrying ATG16L1 var were more frequently males (p = 0.07) and presented a signifcant higher value of fecal calprotectin at diagnosis (p = 0.007). IRGM1 rs4958847 homozygous variant was correlated with a trend toward statistical significance regards to a positive family history (p = 0.078) and the presence of extraintestinal manifestations (p = 0.08). Conclusions: CD patients carrying ATG16L1 var seem to be characterized by a more aggressive disease course, including changes in clinical behaviour, a higher number of relapses and an earlier use of immunosuppressants. IRGM1 rs4958847 variant gene is correlated with a positive family history and with extraintestinal manifestations.