Genetic Analysis of <b><i>TREM2</i></b> Variants in Tunisian Patients with Alzheimer&apos;s Disease

International audienc

Bipolar Disorder and Multiple Sclerosis: A Case Series

Background. The prevalence of psychiatric disturbance for patients with multiple sclerosis (MS) is higher than that observed in other chronic health conditions. We report three cases of MS and bipolar disorder and we discuss the possible etiological hypothesis and treatment options. Observations. All patients fulfilled the McDonald criteria for MS. Two patients were followed up in psychiatry for manic or depressive symptoms before developing MS. A third patient was diagnosed with MS and developed deferred psychotic symptoms. Some clinical and radiological features are highlighted in our patients: one manic episode induced by high dose corticosteroids and one case of a new orbitofrontal MRI lesion concomitant with the emergence of psychiatric symptoms. All patients needed antipsychotic treatment with almost good tolerance for high dose corticosteroids and interferon beta treatment. Conclusions. MRI lesions suggest the possible implication of local MS-related brain damage in development of pure “psychiatric fits” in MS. Genetic susceptibility is another hypothesis for this association. We have noticed that interferon beta treatments were well tolerated while high dose corticosteroids may induce manic fits

Racial and Socioeconomic Disparities in Bladder Cancer Survival: Analysis of the California Cancer Registry

PurposeTo examine the California Cancer Registry (CCR) for bladder cancer survival disparities based on race, socioeconomic status (SES), and insurance in California patients.Patients and methodsThe CCR was queried for bladder cancer cases in California from 1988 to 2012. The primary outcome was disease-specific survival (DSS), defined as the time interval from date of diagnosis to date of death from bladder cancer. Survival analyses were performed to determine the prognostic significance of racial and socioeconomic factors.ResultsA total of 72,452 cases were included (74.5% men, 25.5% women). The median age was 72 years (range, 18-109 years). The racial distribution among the patients was 81% white, 3.8% black, 8.8% Hispanic, 5.2% Asian, and 1.2% from other races. In black patients, tumors presented more frequently with advanced stage and high grade. Medicaid patients tended to be younger and had more advanced-stage, higher-grade tumors compared to patients with Medicare or managed care (P&nbsp;&lt; .0001). Kaplan-Meier analysis demonstrated significantly poorer 5-year DSS in black, low SES, and Medicaid patients (P&nbsp;&lt; .0001). When controlling for stage, grade, age, and gender, multivariate analysis revealed that black race (DSS hazard ratio&nbsp;= 1.295; 95% confidence interval, 1.212-1.384), low SES (DSS hazard ratio&nbsp;= 1.325; 95% confidence interval, 1.259-1.395), and Medicaid insurance (DSS hazard ratio&nbsp;= 1.349; 95% confidence interval, 1.246-1.460) were independent prognostic factors (P&nbsp;&lt; .0001).ConclusionAn analysis of the CCR demonstrated that black race, low SES, and Medicaid insurance portend poorer DSS. These findings reflect a multifaceted socioeconomic and public health conundrum, and efforts to reduce inequalities should be pursued

Early clinical markers of aggressive multiple sclerosis

Patients with the 'aggressive' form of multiple sclerosis accrue disability at an accelerated rate, typically reaching Expanded Disability Status Score (EDSS) ≥ 6 within 10 years of symptom onset. Several clinicodemographic factors have been associated with aggressive multiple sclerosis, but less research has focused on clinical markers that are present in the first year of disease. The development of early predictive models of aggressive multiple sclerosis is essential to optimize treatment in this multiple sclerosis subtype. We evaluated whether patients who will develop aggressive multiple sclerosis can be identified based on early clinical markers. We then replicated this analysis in an independent cohort. Patient data were obtained from the MSBase observational study. Inclusion criteria were (i) first recorded disability score (EDSS) within 12 months of symptom onset; (ii) at least two recorded EDSS scores; and (iii) at least 10 years of observation time, based on time of last recorded EDSS score. Patients were classified as having 'aggressive multiple sclerosis' if all of the following criteria were met: (i) EDSS ≥ 6 reached within 10 years of symptom onset; (ii) EDSS ≥ 6 confirmed and sustained over ≥6 months; and (iii) EDSS ≥ 6 sustained until the end of follow-up. Clinical predictors included patient variables (sex, age at onset, baseline EDSS, disease duration at first visit) and recorded relapses in the first 12 months since disease onset (count, pyramidal signs, bowel-bladder symptoms, cerebellar signs, incomplete relapse recovery, steroid administration, hospitalization). Predictors were evaluated using Bayesian model averaging. Independent validation was performed using data from the Swedish Multiple Sclerosis Registry. Of the 2403 patients identified, 145 were classified as having aggressive multiple sclerosis (6%). Bayesian model averaging identified three statistical predictors: age > 35 at symptom onset, EDSS ≥ 3 in the first year, and the presence of pyramidal signs in the first year. This model significantly predicted aggressive multiple sclerosis [area under the curve (AUC) = 0.80, 95% confidence intervals (CIs): 0.75, 0.84, positive predictive value = 0.15, negative predictive value = 0.98]. The presence of all three signs was strongly predictive, with 32% of such patients meeting aggressive disease criteria. The absence of all three signs was associated with a 1.4% risk. Of the 556 eligible patients in the Swedish Multiple Sclerosis Registry cohort, 34 (6%) met criteria for aggressive multiple sclerosis. The combination of all three signs was also predictive in this cohort (AUC = 0.75, 95% CIs: 0.66, 0.84, positive predictive value = 0.15, negative predictive value = 0.97). Taken together, these findings suggest that older age at symptom onset, greater disability during the first year, and pyramidal signs in the first year are early indicators of aggressive multiple sclerosis

Early predictors of disability in paediatric multiple sclerosis: evidence from a multi-national registry

Background Early recognition of markers of faster disability worsening in paediatric-onset multiple sclerosis (MS) is a key requisite of personalised therapy for children with MS at the earliest possible time. Objective To identify early predictors of rapid disability accrual in patients with paediatric-onset MS. Methods Using the global MSBase registry, we identified patients who were <18 years old at the onset of MS symptoms. The clinico-demographic characteristics examined as predictors of future MS Severity Score (MSSS) included sex, age at symptom onset, absence of disability at the initial assessment, maximum Expanded Disability Status Scale (EDSS) score, relapse frequency and presence of brainstem, pyramidal, visual or cerebellar symptoms in the first year. A Bayesian log-normal generalised linear mixed model adjusted for cumulative proportion of time on higher-efficacy disease-modifying therapies (DMTs) was used to analyse the data. Results 672 patients (70% female) contributing 9357 visits were included. The median age at symptom onset was 16 (quartiles 15-17) years. Older age at symptom onset (exp(beta)=1.10 (95% CI 1.04 to 1.17)), higher EDSS score (1.22 (1.12 to 1.34)) and pyramidal (1.31 (1.11 to 1.55)), visual (1.25 (1.10 to 1.44)) or cerebellar (1.18 (1.01 to 1.38)) symptoms in the first year were associated with higher MSSS. MSSS was reduced by 4% for every 24% increase in the proportion of time on higher-efficacy DMTs (0.96 (0.93 to 0.99)). Conclusions A relatively later onset of MS in childhood, higher disability and pyramidal, visual or cerebellar symptoms during the first year predicted significant worsening in disability in patients with paediatric-onset MS. Persistent treatment with higher-efficacy DMTs was associated with a reduced rate of disability worsening