Broad white matter impairment in multiple system atrophy.

Multiple system atrophy (MSA) is a rare neurodegenerative disorder characterized by the widespread aberrant accumulation of α-synuclein (α-syn). MSA differs from other synucleinopathies such as Parkinson's disease (PD) in that α-syn accumulates primarily in oligodendrocytes, the only source of white matter myelination in the brain. Previous MSA imaging studies have uncovered focal differences in white matter. Here, we sought to build on this work by taking a global perspective on whole brain white matter. In order to do this, in vivo structural imaging and diffusion magnetic resonance imaging were acquired on 26 MSA patients, 26 healthy controls, and 23 PD patients. A refined whole brain approach encompassing the major fiber tracts and the superficial white matter located at the boundary of the cortical mantle was applied. The primary observation was that MSA but not PD patients had whole brain deep and superficial white matter diffusivity abnormalities (p < .001). In addition, in MSA patients, these abnormalities were associated with motor (Unified MSA Rating Scale, Part II) and cognitive functions (Mini-Mental State Examination). The pervasive whole brain abnormalities we observe suggest that there is widespread white matter damage in MSA patients which mirrors the widespread aggregation of α-syn in oligodendrocytes. Importantly, whole brain white matter abnormalities were associated with clinical symptoms, suggesting that white matter impairment may be more central to MSA than previously thought

Sleep deprivation and Modafinil affect cortical sources of resting state electroencephalographic rhythms in healthy young adults

Objective: It has been reported that sleep deprivation affects the neurophysiological mechanisms underpinning the vigilance. Here, we tested the following hypotheses in the PharmaCog project (www.pharmacog.org): (i) sleep deprivation may alter posterior cortical delta and alpha sources of resting state eyes-closed electroencephalographic (rsEEG) rhythms in healthy young adults; (ii) after the sleep deprivation, a vigilance enhancer may recover those rsEEG source markers. Methods: rsEEG data were recorded in 36 healthy young adults before (Pre-sleep deprivation) and after (Post-sleep deprivation) one night of sleep deprivation. In the Post-sleep deprivation, these data were collected after a single dose of PLACEBO or MODAFINIL. rsEEG cortical sources were estimated by eLORETA freeware. Results: In the PLACEBO condition, the sleep deprivation induced an increase and a decrease in posterior delta (2–4 Hz) and alpha (8–13 Hz) source activities, respectively. In the MODAFINIL condition, the vigilance enhancer partially recovered those source activities. Conclusions: The present results suggest that posterior delta and alpha source activities may be both related to the regulation of human brain arousal and vigilance in quiet wakefulness. Significance: Future research in healthy young adults may use this methodology to preselect new symptomatic drug candidates designed to normalize brain arousal and vigilance in seniors with dementia

Interferon β-1a in relapsing multiple sclerosis: four-year extension of the European IFNβ-1a Dose-C omparison Study

Background: Multiple sclerosis (MS) is a chronic disease requiring long-term monitoring of treatment. Objective: To assess the four-year clinical efficacy of intramuscular (IM) IFNb-1a in patients with relapsing MS from the European IFNb-1a Dose-C omparison Study. Methods: Patients who completed 36 months of treatment (Part 1) of the European IFNb-1a Dose-C omparison Study were given the option to continue double-blind treatment with IFNb-1a 30 mcg or 60 mcg IM once weekly (Part 2). Analyses of 48-month data were performed on sustained disability progression, relapses, and neutralizing antibody (NA b) formation. Results: O f 608/802 subjects who completed 36 months of treatment, 493 subjects continued treatment and 446 completed 48 months of treatment and follow-up. IFNb-1a 30 mcg and 60 mcg IM once weekly were equally effective for up to 48 months. There were no significant differences between doses over 48 months on any of the clinical endpoints, including rate of disability progression, cumulative percentage of patients who progressed (48 and 43, respectively), and annual relapse rates; relapses tended to decrease over 48 months. The incidence of patients who were positive for NAbs at any time during the study was low in both treatment groups. Conclusion: C ompared with 60-mcg IM IFNb-1a once weekly, a dose of 30 mcg IM IFNb-1a once weekly maintains the same clinical efficacy over four years

A new MRI rating scale for progressive supranuclear palsy and multiple system atrophy: validity and reliability

AIM To evaluate a standardised MRI acquisition protocol and a new image rating scale for disease severity in patients with progressive supranuclear palsy (PSP) and multiple systems atrophy (MSA) in a large multicentre study. METHODS The MRI protocol consisted of two-dimensional sagittal and axial T1, axial PD, and axial and coronal T2 weighted acquisitions. The 32 item ordinal scale evaluated abnormalities within the basal ganglia and posterior fossa, blind to diagnosis. Among 760 patients in the study population (PSP = 362, MSA = 398), 627 had per protocol images (PSP = 297, MSA = 330). Intra-rater (n = 60) and inter-rater (n = 555) reliability were assessed through Cohen's statistic, and scale structure through principal component analysis (PCA) (n = 441). Internal consistency and reliability were checked. Discriminant and predictive validity of extracted factors and total scores were tested for disease severity as per clinical diagnosis. RESULTS Intra-rater and inter-rater reliability were acceptable for 25 (78%) of the items scored (≥ 0.41). PCA revealed four meaningful clusters of covarying parameters (factor (F) F1: brainstem and cerebellum; F2: midbrain; F3: putamen; F4: other basal ganglia) with good to excellent internal consistency (Cronbach α 0.75-0.93) and moderate to excellent reliability (intraclass coefficient: F1: 0.92; F2: 0.79; F3: 0.71; F4: 0.49). The total score significantly discriminated for disease severity or diagnosis; factorial scores differentially discriminated for disease severity according to diagnosis (PSP: F1-F2; MSA: F2-F3). The total score was significantly related to survival in PSP (p<0.0007) or MSA (p<0.0005), indicating good predictive validity. CONCLUSIONS The scale is suitable for use in the context of multicentre studies and can reliably and consistently measure MRI abnormalities in PSP and MSA. Clinical Trial Registration Number The study protocol was filed in the open clinical trial registry (http://www.clinicaltrials.gov) with ID No NCT00211224

Caractéristiques cliniques et évolution des patients hospitalisés pour une infection au SARS-CoV-2 au CHU de Toulouse. Résultats de la cohorte Covid-clinic-Toul

International audienceBackground. – Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread world-wide from epicenter of Wuhan, China since December 2019. The aim of our study was to describe theclinical characteristics and outcome of hospitalized patients with SARS-CoV-2 pneumonia at the Toulouseuniversity hospital, France.Patients and methods. – We selected the patients included from March 7, 2020 to April 20, 2020 in theretrolective Covid-clinic-Toul cohort that follows all hospitalized patients with SARS-CoV-2 infectionat the Toulouse Hospital. Cases were confirmed by real-time reverse transcriptase polymerase chainreaction. We report demographics, clinical, biological and radiological features, as well as unfavorableoutcome at Day 14 after admission (admission in an intensive care unit, mechanical ventilation, death).Results. – Among 263 hospitalized patients, the median age was 65 years and 155 (58.9%) were males.Two hundred and twenty-seven patients (86.3%) had at least one comorbidity. The median time fromfirst symptom to hospital admission was 7.0 days (interquartile range: 4–10). On day 14 after admission,111 patients (42.2%) had been transferred to intensive care unit (ICU), including 50 (19.0%) on Day 1; 61(23.1%) needed mechanical ventilation and 19 patients (7.2%) had died. Patients admitted to ICU at Day 1of admission (n = 50) were more frequently men (66.0% vs 57.3%), smokers (25.0% vs 7.1%), with obesity(42.0% vs 24.7%) and had a higher mean level of C-reactive protein (median: 110.9 mg/L vs 46.2 mg/L).Conclusion. – This cohort provides epidemiological data on SARS-CoV-2 in hospitalized patients in aUniversity hospital in the South of Franc