Background: Pneumonia with respiratory failure represents the main cause of death in COVID-19, where hyper inflammation plays an important role in lung damage. This study aims to evaluate if tocilizumab, an anti-soluble IL-6 receptor monoclonal antibody, reduces patients' mortality. Methods: 85 consecutive patients admitted to the Montichiari Hospital (Italy) with COVID-19 related pneumonia and respiratory failure, not needing mechanical ventilation, were included if satisfying at least one among: respiratory rate ≥ 30 breaths/min, peripheral capillary oxygen saturation ≤ 93% or PaO2/FiO2<=300 mmHg. Patients admitted before March 13th (n=23) were prescribed the standard therapy (hydroxychloroquine, lopinavir and ritonavir) and were considered controls. On March 13th tocilizumab was available and patients admitted thereafter (n=62) received tocilizumab once within 4 days from admission, plus the standard care. Results: Patients receiving tocilizumab showed significantly greater survival rate as compared to control patients (hazard ratio for death, 0.035; 95% confidence interval [CI], 0.004 to 0.347; p = 0.004), adjusting for baseline clinical characteristics. Two out of 62 patients of the tocilizumab group and 11 out of 23 in the control group died. 92% and 42.1% of the discharged patients in the tocilizumab and control group respectively, recovered. The respiratory function resulted improved in 64.8% of the observations in tocilizumab patients who were still hospitalized, whereas 100% of controls worsened and needed mechanical ventilation. No infections were reported. Conclusions: Tocilizumab results to have a positive impact if used early during Covid-19 pneumonia with severe respiratory syndrome in terms of increased survival and favorable clinical course.

MULTIPLE SCLEROSIS MSJ JOURNAL1258 journals.sagepub.com/home/msj BackgroundCognitive impairment (CI) is known to be present in all stages of multiple sclerosis (MS); however, the prevalence estimates vary considerably between studies, ranging from 40% to 65%. 1 The profile of CI in the overall MS population is now relatively well known, involving mainly complex attention, information processing speed, episodic memory, and executive functions. 1,2 Therefore, brief neuropsychological batteries for MS 3 and newly developed assessment tools 4 mainly focus on the assessment of these functions. However, few studies investigated the differences in the prevalence and profile of CI between the different MS disease subtypes, providing heterogeneous results. [5][6][7][8][9] Many of these studies included small clinical samples and focused mainly on relapsing remitting (RR) or progressive forms. Moreover, the association of CI with several clinical features, such as physical disability, sex, and disease duration, is not well established, since inconsistent results have been reported in the literature. [10][11][12][13] The heterogeneity of the published literature could be, at least in part, attributable to small sample size and dissimilarities in the clinical characteristics of the studies' samples. Exploring the independent effects of age, physical disability, disease duration, and disease subtype could prove central to provide a better understanding of the potential role and interaction of cognitive reserve, brain aging, and disease severity for determining CI in MS. The severity of impairment and the number of involved domains were significantly higher in SP and primary progressive multiple sclerosis (PPMS) than in CIS and RR. In multivariable logistic regression analysis, the presence of CI was significantly associated with higher Expanded Disability Status Scale (EDSS) and older age. Conclusion: CI is present in all MS subtypes since the clinical onset and its frequency is increased in the progressive forms, but these differences seem to be more associated with patient age and physical disability than to disease subtype per se.

Rehabilitation of attention and information processing and executive functions in RR MS may be effected through enhanced recruitment of brain networks subserving the trained functions.

Converging evidence suggests that emotion processing mediated by ventromedial prefrontal cortex (vmPFC) is necessary to prevent personal moral violations. In moral dilemmas, for example, patients with lesions in vmPFC are more willing than normal controls to approve harmful actions that maximize good consequences (e.g., utilitarian moral judgments). Yet, none of the existing studies has measured subjects' emotional responses while they considered moral dilemmas. Therefore, a direct link between emotion processing and moral judgment is still lacking. Here, vmPFC patients and control participants considered moral dilemmas while skin conductance response (SCR) was measured as a somatic index of affective state. Replicating previous evidence, vmPFC patients approved more personal moral violations than did controls. Critically, we found that, unlike control participants, vmPFC patients failed to generate SCRs before endorsing personal moral violations. In addition, such anticipatory SCRs correlated negatively with the frequency of utilitarian judgments in normal participants. These findings provide direct support to the hypothesis that the vmPFC promotes moral behavior by mediating the anticipation of the emotional consequences of personal moral violations.

Central and peripheral nervous system involvement during acute COVID-19 is well known. Although many patients report some subjective symptoms months after the infection, the exact incidence of neurological and cognitive sequelae of COVID-19 remains to be determined. The aim of this study is to investigate if objective neurological or cognitive impairment is detectable four months after SARS-CoV-2 infection, in a group of patients who had mild–moderate COVID-19. A cohort of 120 health care workers previously affected by COVID-19 was examined 4 months after the diagnosis by means of neurological and extensive cognitive evaluation and compared to a group of 30 health care workers who did not have COVID-19 and were similar for age and co morbidities. At 4 month follow-up, 118/120 COVID-19 cases had normal neurological examination, two patients had neurological deficits. COVID-19 patients did not show general cognitive impairment at MMSE. In COVID-19 cases the number of impaired neuropsychological tests was not significantly different from non COVID-19 cases (mean 1.69 and 1 respectively, Mann–Whitney p = n.s.), as well as all the mean tests’ scores. Anxiety, stress and depression scores resulted to be significantly higher in COVID-19 than in non COVID-19 cases. The results do not support the presence of neurological deficits or cognitive impairment in this selected population of mild–moderate COVID-19 patients four months after the diagnosis. Severe emotional disorders in patients who had COVID-19 in the past are confirmed.

In benign multiple sclerosis (BMS), cognitive dysfunction is associated with severe structural brain damage, which resembles that of patients with a much more disabling disease course. A reliable definition of BMS should, therefore, include the preservation of cognitive functioning as an additional requisite.

IMPORTANCECognitive impairment is a common and disabling feature of multiple sclerosis (MS), but a precise characterization of cognitive phenotypes in patients with MS is lacking.OBJECTIVES To identify cognitive phenotypes in a clinical cohort of patients with MS and to characterize their clinical and magnetic resonance imaging (MRI) features. DESIGN, SETTING, AND PARTICIPANTSThis multicenter cross-sectional study consecutively screened clinically stable patients with MS and healthy control individuals at 8 MS centers in Italy from January 1, 2010, to October 31, 2019. Patients with MS and healthy control individuals who were not using psychoactive drugs and had no history of other neurological or medical disorders, learning disability, severe head trauma, and alcohol or drug abuse were enrolled. MAIN OUTCOMES AND MEASURES Participants underwent a neurological examination and a cognitive evaluation with the Rao Brief Repeatable Battery and Stroop Color and Word Test. A subgroup of participants also underwent a brain MRI examination. Latent profile analysis was used on cognitive test z scores to identify cognitive phenotypes. Linear regression and mixed-effects models were used to define clinical and MRI features of each phenotype. RESULTS A total of 1212 patients with MS (mean [SD] age, 41.1 [11.1] years; 784 women [64.7%]) and 196 healthy control individuals (mean [SD] age, 40.4 [8.6] years; 130 women [66.3%]) were analyzed in this study. Five cognitive phenotypes were identified: preserved cognition (n = 235 patients [19.4%]), mild-verbal memory/semantic fluency (n = 362 patients [29.9%]), mild-multidomain (n = 236 patients [19.5%]), severe-executive/attention (n = 167 patients [13.8%]), and severe-multidomain (n = 212 patients [17.5%]) involvement. Patients with preserved cognition and mild-verbal memory/semantic fluency were younger (mean [SD] age, 36.5 [9.8] years and 38.2 [11.1] years) and had shorter disease duration (mean [SD] 8.0 [7.3] years and 8.3 [7.6] years) compared with patients with mild-multidomain (mean [SD] age, 42.6 [11.2] years; mean [SD] disease duration, 12.8 [9.6] years; P < .001), severe-executive/attention (mean [SD] age, 42.9 [11.7] years; mean [SD] disease duration, 12.2 [9.5] years; P < .001), and severe-multidomain (mean [SD] age, 44.0 [11.0] years; mean [SD] disease duration , 13.3 [10.2] years; P < .001) phenotypes. Severe cognitive phenotypes prevailed in patients with progressive MS. At MRI evaluation, compared with those with preserved cognition, patients with mild-verbal memory/semantic fluency exhibited decreased mean (SE) hippocampal volume (5.42 [0.68] mL vs 5.13 [0.68] mL; P = .04), patients with the mild-multidomain phenotype had decreased mean (SE) cortical gray matter volume (687.69 [35.40] mL vs 662.59 [35.48] mL; P = .02), patients with severe-executive/ attention had higher mean (SE) T2-hyperintense lesion volume (51.33 [31.15] mL vs 99.69 [34.07] mL; P = .04), and patients with the severe-multidomain phenotype had extensive brain damage, with decreased volume in a...

We investigated how resting state (RS) functional connectivity (FC) of the anterior cingulate cortex (ACC) correlates with cognitive rehabilitation in relapsing remitting multiple sclerosis (RRMS) patients. A neuropsychological assessment and RS fMRI at baseline and after 12 weeks were obtained from 20 RRMS patients, who were assigned randomly to undergo treatment (n = 10) (treatment group-TG), which entailed computer-assisted cognitive rehabilitation of attention/information processing and executive functions for 3 days/week, or not to receive any cognitive rehabilitation (n = 10) (control group-CG). Voxel-wise changes of ACC RS FC were assessed using SPM8. In both groups, at the two study time points, ACC activity was correlated with the bilateral middle and inferior frontal gyrus, basal ganglia, posterior cingulate cortex, cerebellum, precuneus, middle temporal gyrus, and inferior parietal lobule (IPL). At follow up, compared to baseline, the TG showed an increased FC of the ACC with the right middle frontal gyrus (MFG) and right IPL, while the CG showed a decreased FC of the ACC with the right cerebellum and right inferior temporal gyrus (ITG). A significant "treatment × time" interaction was found for the increased FC of the right IPL and for the decreased FC of the right ITG. In the TG only, significant correlations (p < 0.001) were found between improvement of PASAT performance and RS FC of the ACC with the right MFG (r = 0.88) and right IPL (r = 0.76). In MS, cognitive rehabilitation correlates with changes in RS FC of brain regions subserving the trained functions. fMRI might be useful to monitor rehabilitative strategies in MS.