Antibodies against the flotillin-1/2 complex in patients with multiple sclerosis

Lleixa and Caballero-avila et al. report that antibodies targeting the flotillin-1/2 complex are present in a subgroup of patients with multiple sclerosis. Further studies are needed to understand the clinical and pathological relevance of anti-flotillin-1/2 autoantibodies in multiple sclerosis. Multiple sclerosis is a tissue-specific autoimmune disease of the central nervous system in which the antigen(s) remains elusive. Antibodies targeting the flotillin-1/2 complex have been described in 1-2% of the patients in a recent study. Other candidate antigens as anoctamin-2 or neurofascin-155 have been previously described in multiple sclerosis patients, although their clinical relevance remains uncertain. Our study aims to analyse the frequency and clinical relevance of antibodies against neurofascin-155, anoctamin-2 and flotillin-1/2 complex in multiple sclerosis. Serum (n = 252) and CSF (n = 50) samples from 282 multiple sclerosis patients were included in the study. The control group was composed of 260 serum samples (71 healthy donors and 189 with other neuroinflammatory disorders). Anti-flotillin-1/2, anti-anoctamin-2 and anti-neurofascin-155 antibodies were tested by cell-based assays using transfected cells. We identified six multiple sclerosis patients with antibodies against the flotillin-1/2 complex (2.1%) and one multiple sclerosis patient with antibodies against anoctamin-2 (0.35%). All multiple sclerosis patients were negative for anti-neurofascin-155 antibodies. Three of the anti-flotillin-1/2 positive patients showed anti-flotillin-1/2 positivity in other serum samples extracted at different moments of their disease. Immunoglobulin G subclasses of anti-flotillin-1/2 antibodies were predominantly one and three. We confirm that antibodies targeting the flotillin-1/2 complex are present in a subgroup of patients with multiple sclerosis. Further studies are needed to understand the clinical and pathological relevance of anti-flotillin-1/2 autoantibodies in multiple sclerosis

Deep brain stimulation of the subcallosal cingulate gyrus: Further evidence in treatment-resistant major depression

Deep brain stimulation (DBS) is currently tested as an experimental therapy for patients with treatment-resistant depression (TRD). Here we report on the short-and long-term (1 yr) clinical outcomes and tolerance of DBS in eight TRD patients. Electrodes were implanted bilaterally in the subgenual cingulate gyrus (SCG; Broadman areas 24-25), and stimulated at 135 Hz (90-μs pulsewidth). Voltage and active electrode contacts were adjusted to maximize short-term responses. Clinical assessments included the 17-item Hamilton Depression Rating Scale (HAMD17; primary measure), the Montgomery-Ãsberg Depression Rating Scale (MADRS) and the Clinical Global Impression (CGI) Scale. In the first week after surgery, response and remission (HAMD ≤7) rates were, respectively 87.5% and 50%. These early responses were followed by an overall worsening, with a response and remission rates of 37.5% (3/8) at 1 month. From then onwards, patients showed a progressive improvement, with response and remission rates of 87.5% and 37.5%, respectively, at 6 months. The corresponding figures at 1 yr were 62.5% and 50%, respectively. Clinical effects were seen in all HAMD subscales without a significant incidence of side-effects. Surgical procedure and post-operative period were well-tolerated for all patients. This is the second independent study on the use of DBS of the SCG to treat chronic depression resistant to current therapeutic strategies. DBS fully remitted 50% of the patients at 1 yr, supporting its validity as a new therapeutic strategy for TRD. © 2011 CINP.This study is funded by the Fondo de Investigación Sanitaria (FIS: PI 06/0662, PS 09/00580), Instituto Carlos III, and by the Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) intramural funding (P91G), the “VI Plan Nacional I+D+I 2008-2011”, and the “Iniciativa Ingenio 2010, programa CONSOLIDER, acción CIBER”. Support from grant SAF2007-62378 is also acknowledged. Dr. Portella is funded by the Spanish Ministry of Science and Innovation and the Instituto de Investigación Carlos III through a “Miguel Servet” research contract, co-financed by the European Regional Development Fund (ERDF) (2007-2013).Peer Reviewe

Hyponatremia is a risk factor of hepatic encephalopathy in patients with cirrhosis: A prospective study with time-dependent analysis

OBJECTIVES:The aim of this study was to investigate whether hyponatremia is a risk factor of overt hepatic encephalopathy (HE) in cirrhosis.METHODS:A total of 61 patients with cirrhosis were evaluated prospectively for 1 year and all episodes of overt HE were recorded. Predictive factors of HE were analyzed using a conditional model (Prentice, Williams, and Peterson) for recurrent events to assess the relationship between HE and time-dependent covariates. The effects of hyponatremia on the brain concentration of organic osmolytes were analyzed in 25 patients using 1H-magnetic resonance spectroscopy.RESULTS:Twenty- eight of the 61 patients developed 57 episodes of overt HE during follow-up. Among a number of clinical and laboratory variables analyzed, the only independent predictive factors of overt HE were hyponatremia (serum sodium <130mEql), history of overt HE, serum bilirubin, and serum creatinine. Hyponatremia was associated with low brain concentration of organic osmolytes, particularly myo-inositol (MI). Furthermore, patients with low brain MI levels had a higher probability of development of overt HE compared with that of patients with high brain MI levels.CONCLUSIONS:In patients with cirrhosis, the existence of hyponatremia is a major risk factor of the development of overt HE. Treatment of hyponatremia may be a novel therapeutic approach to preventing HE in cirrhosis. © 2009 by the American College of Gastroenterology.Peer Reviewe

Neuropsychological deficits in patients with cognitive complaints after COVID-19

Background: While much of the scientific focus thus far has been on cognitive sequelae in patients with severe COVID-19, subjective cognitive complaints are being reported across the spectrum of disease severity, with recent studies beginning to corroborate patients’ perceived deficits. In response to this, the aims of this study were to (1) explore the frequency of impaired performance across cognitive domains in post-COVID patients with subjective complaints and (2) uncover whether impairment existed within a single domain or across multiple. Methods: Sixty-three patients with subjective cognitive complaints post-COVID were assessed with a comprehensive protocol consisting of various neuropsychological tests and mood measures. Cognitive test performance was transformed into T scores and classified based on recommended guidelines. After performing a principal component analysis to define cognitive domain factors, distributions of test scores within and across domains were analyzed. Results: Results revealed pervasive impact on attention abilities, both as the singularly affected domain (19% of single-domain impairment) as well as coupled with decreased performance in executive functions, learning, and long-term memory. These salient attentional and associated executive deficits were largely unrelated to clinical factors such as hospitalization, disease duration, biomarkers, or affective measures. Discussion: These findings stress the importance of comprehensive evaluation and intervention to address cognitive sequelae in post-COVID patients of varying disease courses, not just those who were hospitalized or experienced severe symptoms. Future studies should investigate to what extent these cognitive abilities are recuperated over time as well as employ neuroimaging techniques to uncover underlying mechanisms of neural damage

Evolving Trends in Neuropsychological Profiles of Post COVID-19 Condition: A 1-Year Follow-up in Individuals with Cognitive Complaints

Background: Cognitive difficulties are reported as lasting sequelae within post COVID-19 condition. However, the chronicity of these difficulties and related factors of fatigue, mood, and perceived health have yet to be fully determined. More longitudinal studies are needed to clarify the trends of cognitive test performance and cognitive domain impairment following COVID-19 onset, and whether hospitalization influences outcomes. Methods: 57 participants who reported subjective cognitive difficulties after confirmed COVID-19 infection were assessed at baseline (~6 months post COVID-19) and follow-up (~15 months later) visits. Assessments included measures across multiple cognitive domains and self-report questionnaires of fatigue, mood, and overall health. Analyses were conducted in three stages: at the test score level (raw and adjusted scores), at the cognitive domain level, and stratified by hospitalization status during infection. Results: Impacts on cognitive test scores remain stable across assessments. Cognitive domain analyses indicate significant reductions in attention and executive functioning impairment, while memory impairment is slower resolve. On self-report measures, there was a significant improvement in overall health ratings at follow-up. Finally, those hospitalized during infection performed worse on timed cognitive measures across visits and accounted for a larger proportion of cases with short-term and working memory impairment at follow-up. Conclusions: Cognitive difficulties persist both at test score and cognitive domain levels in many cases of post COVID-19 condition, but evidence suggests some improvement in global measures of attention, executive functioning and overall self-rated health. An effect of hospitalization on cognitive symptoms post COVID-19 may be more discernible over time

Atypical astroglial pTDP-43 pathology in astroglial predominant tauopathy

Data de publicació electrònica: 17-03-2021We observed atypical astrocytic pTDP-43 pathology in astroglial predominant tauopathy

Soft-dielectron excess in proton–proton collisions at √s = 13 TeV

A measurement of dielectron production in proton-proton (pp) collisions at s√=13 TeV, recorded with the ALICE detector at the CERN LHC, is presented in this Letter. The data set was recorded with a reduced magnetic solenoid field. This enables the investigation of a kinematic domain at low dielectron invariant mass mee and pair transverse momentum pT,ee that was previously inaccessible at the LHC. The cross section for dielectron production is studied as a function of mee, pT,ee, and event multiplicity dNch/dη. The expected dielectron rate from hadron decays, called hadronic cocktail, utilizes a parametrization of the measured η/π0 ratio in pp and proton-nucleus (p-A) collisions, assuming that this ratio shows no strong dependence on collision energy at low transverse momentum. Comparison of the measured dielectron yield to the hadronic cocktail at 0.15<mee<0.6 GeV/c2 and for pT,ee<0.4 GeV/c indicates an enhancement of soft dielectrons, reminiscent of the 'anomalous' soft-photon and -dilepton excess in hadron-hadron collisions reported by several experiments under different experimental conditions. The enhancement factor over the hadronic cocktail amounts to 1.61±0.13(stat.)±0.17(syst.,data)±0.34(syst.,cocktail) in the ALICE acceptance. Acceptance-corrected excess spectra in mee and pT,ee are extracted and compared with calculations of dielectron production from hadronic bremsstrahlung and thermal radiation within a hadronic many-body approach