IntroductionAs cognitive-driven worsening of activities of the daily living (ADL) in Parkinson’s disease (PD) is the core feature of PD dementia (PDD), there is great need for sensitive quantitative assessment. Aim of our study was the evaluation of cognitive-driven worsening of ADL by the performance-based Multiple Object Test (MOT), offering an essential clinical advantage as it is quick and easy to apply in a clinical context even on severely impaired patients.Methods73 PD patients were assessed longitudinally over a period of 37 (6–49) months. According to their neuropsychological profile the sample was divided into two groups: PD patients with (n = 34, PD-CI) and without cognitive impairment (n = 39, PD-noCI). The MOT comprises five routine tasks (e.g. to make coffee) quick and easy to apply. Quantitative (total error number, processing time) and qualitative parameters (error type) were analyzed using non-parametric test statistic (e.g.Wilcoxon signed-rank test, binary logistic regression).ResultsMedian number of total errors (p = 0.001), processing time (p<0.001), perplexity (p = 0.035), and omission errors (p<0.001) increased significantly from baseline to follow-up in the total sample. Worsening of MOT performance was correlated to cognitive decline in the attention/ executive function and visuo-constructive domain. PD-CI showed an increase in omission errors (p = 0.027) compared to PD-noCI over time. This increase in omission errors between visits was further identified as a risk marker for PDD conversion.ConclusionThe MOT, especially frequency of omission errors, is a promising tool to rate PD patients objectively and might help to identify patients with a high risk for having mild cognitive impairment or dementia.

Background: Thromboembolism and bleeding contribute to Coronavirus disease 2019 (COVID-19)’s morbidity and mortality and are also frequent complications of venovenous extracorporeal membrane oxygenation (vvECMO). As the interaction of the underlying pathologies caused by vvECMO in COVID-19 is barely understood, we designed this study to better differentiate coagulation disorders in COVID-19 patients before, during and after vvECMO-support. Methods: Observational case series, six consecutive patients with Coronavirus acute respiratory distress syndrome supported with vvECMO treated in the anaesthesiologic ICU in a third level University ECMO-centre. We measured routine coagulation parameters and assessed coagulation factors. We also conducted advanced von Willebrand factor (VWF) multimer analysis, platelet aggregometry and immunological screening. Results: We identified various phases of coagulation disorders: Initially, intensely activated coagulation with highly increased VWF and factor VIII activity in acute COVID-19, then severe acquired von Willebrand syndrome and platelet dysfunction during vvECMO leading to spontaneous bleeding and finally, hypercoagulopathy after vvECMO explantation. Five of six patients developed immunological abnormalities enhancing coagulation. Conclusions: Coronavirus-induced coagulopathy and bleeding disorders during vvECMO cannot be discriminated via ‘routine’ coagulation tests. Precise and specific analyses followed by the appropriate treatment of coagulation disorders may help us develop tailored therapeutic concepts to better manage the phases described above.

The GNE gene encodes an enzyme that initiates and regulates the biosynthesis of N-acetylneuraminic acid, a precursor of sialic acids. GNE mutations are classically associated with Nonaka myopathy and sialuria, following an autosomal recessive and autosomal dominant inheritance pattern. Reports show that single GNE variants cause severe thrombocytopenia without muscle weakness. Using panel sequencing, we identified two novel compound heterozygous variants in GNE in a young girl with life-threatening bleedings, severe congenital thrombocytopenia, and a platelet secretion defect. Both variants are located in the nucleotide-binding site of the N-acetylmannosamin kinase domain of GNE. Lectin array showed decreased α-2,3-sialylation on platelets, consistent with loss of sialic acid synthesis and indicative of rapid platelet clearance. Hematopoietic stem cell transplantation (HSCT) normalized platelet counts. This is the first report of an HSCT in a patient with an inherited GNE defect leading to normal platelet counts.