Head-to-head comparison of treatment modalities such as VNS, DBS and RNS across different epileptic syndromes are required to decide which treatment modality is the most effective for a given patient scenario. Such studies are challenging and it is unlikely that data will be available in the near future. Additional data collection on potentially promising noninvasive neurostimulation modalities like tVNS, TMS, TNS and tDCS is warranted to get a more precise estimate of their therapeutic benefit and long-term safety.

Background and purpose Dysphagia, dysarthria and aphasia are common symptoms following acute stroke; however, limited data are available from recent prospective clinical trials. The aim of this study was to determine the incidence and associated factors of dysphagia, dysarthria and aphasia following a first acute ischaemic stroke in patients admitted to a comprehensive stroke center. Methods All first ischaemic stroke patients admitted to the Stroke Unit of Ghent University Hospital within 48 h after symptom onset were enrolled in this prospective study between March 2018 and October 2019. Dysphagia and communication screenings were performed within 3 days after admission. When dysphagia, dysarthria and/or aphasia were assumed, standardized assessments were performed. Incidence rates were calculated as point estimates (%) with 95% confidence intervals (CI). Associated factors were calculated via multivariate binary logistic regression analyses. Results Dysphagia, dysarthria and aphasia were present in 23% (95% CI, 17–31), 44% (95% CI, 37–52) and 23% (95% CI, 17–30), respectively of 151 first ischaemic stroke patients [67 female, mean age 67 (SD 14) years]. Separate multivariate binary logistic regression analyses showed that dysphagia, dysarthria and aphasia were significantly associated with age‐adjusted stroke severity at baseline [odds ratio (OR), 1.16; 95% CI, 1.09–1.23; OR, 1.13; 95% CI, 1.07–1.20 and OR, 1.11; 95% CI, 1.05–1.17 respectively]. Corrected for stroke severity, the risk for aphasia increased by 4% per year of age (OR, 1.04; 95% CI, 1.00–1.07). Adjusted for age and stroke severity, aphasia was significantly associated with large artery atherosclerosis as stroke etiology (OR, 3.91; 95% CI, 1.18–12.98). Conclusions This trial showed a high incidence of dysphagia, dysarthria and aphasia following acute ischaemic stroke. Stroke severity was an associated factor for all three symptoms.

secretion and contributes to thrombotic thrombocytopenic purpura in mice. J Thromb Haemost 2015; 13: 283-92.Summary. Background: Congenital thrombotic thrombocytopenic purpura (TTP) is characterized by mutations in the ADAMTS13 gene, which either impair protein secretion or influence ADAMTS13 (A Disintegrin-like And Metalloprotease domain with ThromboSpondin type-1 motif, member 13) activity. Phenotypic consequences of these mutations have not yet been evaluated in animal models for TTP. Objectives: To identify the in vitro effect of a novel ADAMTS13 mutation and to investigate whether this mutation induces TTP in vivo. Methods: All 29 ADAMTS13 exons with exon-intron boundaries of a patient with pregnancy-onset TTP were sequenced. Wildtype and mutant ADAMTS13 proteins were both transiently and stably expressed in human embryonic kidney cells, and their activity was evaluated in vitro using fluorescence resonance energy transfer and flow assays. Molecular dynamics simulations were performed to study Ca 2+ stability. Adamts13 -/-mice were hydrodynamically injected with wild-type and mutant expression plasmids and triggered with recombinant human von Willebrand factor. Results: We identified a novel heterozygous c.559G>C mutation in exon 6 of the proposita's ADAM-TS13 gene. This mutation resulted in a p.Asp187His substitution (p.D187H), which was located in the high affinity Ca 2+ -binding site in the metalloprotease domain of ADAMTS13. The homozygous p.D187H mutation down-regulated ADAMTS13 activity in vitro. Impaired proteolytic activity was linked to unstable Ca 2+ binding as visualized using a molecular dynamics simulation. In addition, the p.D187H mutation affects protein secretion in vitro. In Adamts13 -/-mice, the homozygous p.D187H mutation reduced ADAMTS13 secretion and activity and contributed to TTP when these mice were triggered with recombinant human von Willebrand factor. Conclusions: Our data indicate that the p.D187H mutation impairs ADAMTS13 activity and secretion and is responsible for TTP onset in mice.

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening thrombotic microangiopathy linked to a deficiency in the metalloprotease ADAMTS13. In the current study, a novel mouse model for acquired TTP was generated to facilitate development and validation of new therapies for this disease. Therefore, a large panel (n = 19) of novel anti-mouse ADAMTS13 (mADAMTS13) monoclonal antibodies (mAbs) of mouse origin was generated. Inhibitory anti-mADAMTS13 mAbs were identified using the FRETS-VWF73 assay. Four mAbs strongly inhibited mADAMTS13 activity in vitro (∼68–90% inhibition). Injecting a combination of 2 inhibitory mAbs (13B4 and 14H7, 1.25 mg/kg each) in Adamts13+/+ mice resulted in full inhibition of plasma ADAMTS13 activity (96 ± 4% inhibition, day 1 post injection), leading to the appearance of ultra-large von Willebrand factor (UL-VWF) multimers. Interestingly, the inhibitory anti-mADAMTS13 mAbs 13B4 and 14H7 were ideally suited to induce long-term ADAMTS13 deficiency in Adamts13+/+ mice. A single bolus injection resulted in full ex vivo inhibition for more than 7 days. As expected, the mice with the acquired ADAMTS13 deficiency did not spontaneously develop TTP, despite the accumulation of UL-VWF multimers. In line with the Adamts13-/- mice, TTP-like symptoms could only be induced when an additional trigger (rVWF) was administered. On the other hand, the availability of our panel of anti-mADAMTS13 mAbs allowed us to further develop a sensitive ELISA to detect ADAMTS13 in mouse plasma. In conclusion, a novel acquired TTP mouse model was generated through the development of inhibitory anti-mADAMTS13 mAbs. Consequently, this model provides new opportunities for the development and validation of novel treatments for patients with TTP. In addition, these newly developed inhibitory anti-mADAMTS13 mAbs are of great value to specifically study the role of ADAMTS13 in mouse models of thrombo-inflammatory disease.