Objectives:The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is considered to have potential neuro-invasiveness that might lead to acute brain disorders or contribute to respiratory distress in patients with coronavirus disease 2019 (COVID-19). This study investigates the occurrence of structural brain abnormalities in non-survivors of COVID-19 in a virtopsy framework.Methods:In this prospective, monocentric, case series study, consecutive patients who fulfilled the following inclusion criteria benefited from an early postmortem structural brain MRI: death <24 hours, SARS-CoV-2 detection on nasopharyngeal swab specimen, chest computerized tomographic (CT) scan suggestive of COVID-19, absence of known focal brain lesion, and MRI compatibility.Results:Among the 62 patients who died from COVID-19 from 31/03/2020 to 24/04/2020 at our institution, 19 decedents fulfilled the inclusion criteria. Parenchymal brain abnormalities were observed in 4 decedents: subcortical micro- and macro-bleeds (2 decedents), cortico-subcortical edematous changes evocative of posterior reversible encephalopathy syndrome (PRES, one decedent), and nonspecific deep white matter changes (one decedent). Asymmetric olfactory bulbs were found in 4 other decedents without downstream olfactory tract abnormalities. No brainstem MRI signal abnormality was observed.Conclusions:Postmortem brain MRI demonstrates hemorrhagic and PRES-related brain lesions in non-survivors of COVID-19. SARS-CoV-2-related olfactory impairment seems to be limited to olfactory bulbs. Brainstem MRI findings do not support a brain-related contribution to respiratory distress in COVID-19.

ImportanceThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is considered to have potential neuro-invasiveness that might lead to acute brain disorders or contribute to respiratory distress in patients with coronavirus disease 2019 (COVID-19). Brain magnetic resonance imaging (MRI) data in COVID-19 patients are scarce due to difficulties to obtain such examination in infected unstable patients during the COVID-19 outbreak.ObjectiveTo investigate the occurrence of structural brain abnormalities in non-survivors of COVID-19 in a virtopsy framework.DesignProspective, case series study with postmortem brain MRI obtained early (<24h) after death.SettingMonocentric study.ParticipantsFrom 31/03/2020 to 24/04/2020, consecutive decedents who fulfilled the following inclusion criteria were included: death <24 hours, SARS-CoV-2 detection on nasopharyngeal swab specimen, chest computerized tomographic (CT) scan suggestive of COVID-19, absence of known focal brain lesion, and MRI compatibility.Main Outcome(s) andMeasure(s)Signs of acute brain injury and MRI signal abnormalities along the olfactory tract and brainstem were searched independently by 3 neuroradiologists, then reviewed with neurologists and clinicians.ResultsAmong the 62 patients who died from COVID-19 during the inclusion period, 19 decedents fulfilled inclusion criteria. Subcortical micro- and macro-bleeds (2 decedents), cortico-subcortical edematous changes evocative of posterior reversible encephalopathy syndrome (PRES, one decedent), and nonspecific deep white matter changes (one decedent) were observed. Asymmetric olfactory bulbs were found in 4 other decedents without downstream olfactory tract abnormalities. No brainstem MRI signal abnormality.Conclusions and RelevancePostmortem brain MRI demonstrates hemorrhagic and PRES-related brain lesions in non-survivors of COVID-19 that might be triggered by the virus-induced endothelial disturbances. SARS-CoV-2-related olfactory impairment seems to be limited to olfactory bulbs. The absence of brainstem MRI abnormalities does not support a brain-related contribution to respiratory distress in COVID-19.Key PointsQuestionIs there common brain MRI abnormalities patterns in non-survivors of coronavirus disease 2019 ?FindingsIn a case series of 19 non-survivors of severe COVID-19 disease, early postmortem brain MRI demonstrated patterns evocative of intracranial vasculopathy in 4 decedents: subcortical micro- and macro-bleeds (2 decedents), cortico-subcortical edematous changes evocative of posterior reversible encephalopathy syndrome (PRES, one decedent), and nonspecific deep white matter changes (one decedent). Asymmetric olfactory bulbs were found in 4 other decedents but without downstream olfactory tract abnormalities.MeaningPostmortem brain MRI demonstrates hemorrhagic and PRES-related brain lesions in non-survivors of COVID-19 that might be triggered by virus-induced endothelial disturbances.

OBJECTIVE -Corrected QT (QTc) prolongation is predictive of cardiovascular mortality in both the general and diabetic populations. As part of the EURODIAB Prospective Complication Study, we have assessed the 7-year incidence and risk factors of prolonged QTc in people with type 1 diabetes. RESEARCH DESIGN AND METHODS-A total of 1,415 type 1 diabetic subjects, who had normal QTc at baseline, were reanalyzed after the 7-year follow-up period. QTc Ͼ0.44 s was considered abnormally prolonged.RESULTS -Cumulative incidence of prolonged QTc was 18.7%, which is twofold higher in women than in men (24.5 vs. 13.9%, P Ͻ 0.0001). At the baseline examination, incident cases were older and less physically active than nonincident cases, had higher mean values of systolic blood pressure and HDL cholesterol, and had higher frequencies of hypertension, coronary heart disease, and distal symmetrical polyneuropathy. In multivariate logistic regression analyses, female sex and higher values of A1C and systolic blood pressure were associated with the risk of prolonged QTc, whereas physical activity and BMI within the range of 21.5-23.2 kg/m 2 were protective factors. In women, association with modifiable factors, particularly BMI, was stronger than in men.CONCLUSIONS -In type 1 diabetic subjects from the EURODIAB cohort, female sex, A1C, and systolic blood pressure are predictive of prolonged QTc, whereas physical activity and BMI within the range of 21.5-23.2 kg/m 2 play a protective role. These findings are clinically relevant, as they may help to identify subjects at higher risk for prolonged QTc, as well as provide potential targets for risk-lowering strategies.

The aim of emergency imaging is to detect treatable lesions before secondary neurological damage occurs. CT plays a primary role in the acute setting of head trauma, allowing accurate detection of lesions requiring immediate neurosurgical treatment. CT is also accurate in detecting secondary injuries and is therefore essential in follow-up. This review discusses the main characteristics of primary and secondary brain injuries.

Levels of serum heat shock protein 27 (sHsp27) have been studied in numerous cancer types, but their potential relevance in patients with hepatocellular carcinoma (HCC) is undetermined. Our aim was to compare sHsp27 levels in patients with HCC and HCC-free controls. Specifically, we recruited 71 patients with HCC (80 % with early tumour), 80 patients with chronic liver disease (59 with liver cirrhosis and 21 with chronic active hepatitis) and 42 healthy subjects. sHsp27 was measured by immunoenzymatic assay. Results showed that sHsp27 levels were significantly (p<0.001) higher in patients with HCC than in the other groups, particularly in those with hepatitis C virus (HCV)-related disease. In HCC patients, sHsp27 levels were not associated with prognostic risk factors, such as size/ multiplicity of nodules and stage. In logistic regression analysis, performed in patients with liver disease, logsHsp27 was associated with a significant age-adjusted 2.5-fold increased odds ratio of HCC and with a significant 4.4-fold higher odds ratio of HCC in the subgroup with HCVrelated liver disease. In receiver operating characteristic curve analysis, sensitivity and specificity of the best sHsp27 cut-off value (456.5 pg/ml) for differentiating patients with HCC from those with HCC-free chronic liver disease were 70 and 73 %, respectively. In conclusion, sHsp27 levels are enhanced in patients with HCC and may represent a candidate biomarker of HCC.

Background: The central vein sign (CVS) is an imaging biomarker able to differentiate multiple sclerosis (MS) from other conditions causing similar appearance lesions on magnetic resonance imaging (MRI), including cerebral small vessel disease (CSVD). However, the impact of vascular risk factors (VRFs) for CSVD on the percentage of CVS positive (CVS+) lesions in MS has never been evaluated. Objective: To investigate the association between different VRFs and the percentage of CVS+ lesions in MS. Methods: In 50 MS patients, 3T brain MRIs (including high-resolution 3-dimensional T2*-weighted images) were analyzed for the presence of the CVS and MRI markers of CSVD. A backward stepwise regression model was used to predict the combined predictive effect of VRF (i.e. age, hypertension, diabetes, obesity, ever-smoking, and hypercholesterolemia) and MRI markers of CSVD on the CVS. Results: The median frequency of CVS+ lesions was 71% (range: 35%–100%). In univariate analysis, age ( p < 0.0001), hypertension ( p < 0.001), diabetes ( p < 0.01), obesity ( p < 0.01), smoking ( p < 0.05), and the presence of enlarged-perivascular-spaces on MRI ( p < 0.005) were all associated with a lower percentage of CVS+ lesions. The stepwise regression model showed that age and arterial hypertension were both associated with the percentage of CVS+ lesions in MS (adjusted R2 = 0.46; p < 0.0001 and p = 0.01, respectively). Conclusion: The proportion of CVS+ lesions significantly decreases in older and hypertensive MS patients. Although this study was conducted in patients with an already established MS diagnosis, the diagnostic yield of the previously proposed 35% CVS proportion-based diagnostic threshold appears to be not affected. Overall these results suggest that the presence of VRF for CSVD should be taken into account during the CVS assessment.

Background: Two major concerns with respect to task-based motor functional magnetic resonance imaging (fMRI) are inadequate participants' performance as well as intra-and inter-subject variability in execution of the motor action. New method: This study validates the use of an MRI-compatible stimulator based on a pneumatic artificial muscle (PAM) for block-design fMRI mapping of the primary sensorimotor (SM1) cortex in a series of fifteen right-handed healthy subjects. The PAM stimulator elicits computer-controlled timely and reproducible passive movements of fingers/toes. Participants performed comparable active and passive PAM-induced flexion-extensions of the index fingers. Results: Passive movement of the right index finger and passive alternating right and left index finger movement resulted in a significant increase in blood-oxygen-level-dependent (BOLD) signal in contralateral SM1 cortex in 14/15 and 15/15 subjects respectively. Similar networks were recruited by active and passive index finger movements. However, at the group level, active movement induced significantly higher increases in BOLD signal than passive movement in contralateral SM1 cortex (p < 0.05 Family Wise Error [FWE] corrected), supplementary motor area (p < 0.001 uncorrected), ipsilateral cerebellum (p < 0.001 uncorrected), and bilateral putamina (p < 0.001 uncorrected). Comparison with existing method(s): As compared to the several MRI-compatible robotic devices for computercontrolled passive movement of the fingers that were introduced in the past decades, the proposed PAM-based stimulator is smaller, handier, and easier to use in the MRI setting. Conclusions: PAM-based stimulators can be reliably used for passive sensorimotor fMRI mapping in healthy subjects. Using this approach, bilateral SM1 cortices can be mapped accurately during a single 6-min blockdesign fMRI protocol.

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