clinicaltrials.gov Identifier: NCT01829581.

To investigate the circadian rhythm of inducible cytokine release and a potential pacemaker role of endogenous cortisol, cortisol levels as well as cytokine release from ex vivo LPS-stimulated blood were assessed at 4-h intervals over 24 h in 11 volunteers. We found a significant diurnal variation for IFN-c and IL-8, and a tendency for TNF, all inversely correlated to the serum cortisol levels, but no evidence for such a rhythm for IL-1b and IL-6. In vitro IC 50 values for cytokine inhibition by hydrocortisone (HC) corresponded to the observed rank order for circadian rhythmicity. mRNA analyses revealed that this was due to a reduction of gene transcription. These effects of HC were significantly reversed by the glucocorticoid receptor antagonist RU486. Supplementation of HC in vivo to maintain morning cortisol levels throughout the day blunted the circadian rhythm of ex vivo LPS-induced cytokines. Surprisingly, no significant diurnal variation for any investigated cytokine was found in the same volunteer group upon stimulation with lipoteichoic acid (LTA), the gram-positive counterpart to LPS. Furthermore, 10-50-fold higher HC concentrations as compared to LPS were required to block LTA-induced cytokine release. LTA, in contrast to LPS, failed to activate Jun kinase, a reported target for HC action.

Background: Angioedema (AE) in stroke has been reported exclusively after thrombolysis with recombinant tissue-type plasminogen activator (rtPA). Previous studies proposed the insular cortex to play a specific role in the development of AE after stroke. We evaluated the incidence of AE in acute stroke and tried to identify the predominantly involved brain structures. Methods: We performed a retrospective search of our stroke database for patients with an AE. MRI data were analyzed by adapting the images to a standard size and superimposing the infarctions. The areas of overlap were assumed to represent the areas of interest. Results: 865 of 4,789 (18.1%) consecutive patients with acute stroke received IV rtPA, 20 of them (2.3%) developed AE. One patient developed AE without prior thrombolysis. The odds ratio for AE after rtPA was 93 (95% CI: 12-693). Of the 21 AE patients, 15 (71.4%) had ACE-inhibitor treatment (ACEi) and 7 (33.3%) had diabetes. In all but one patient, AE was clearly lateralized; then the AE was contralateral to the side of the ischemia in 18 of 20 patients (90.0%). An insular/peri-insular involvement was detected in 17/21 (81.0%). About 80.0% of the patients had a suspected MCA branch occlusion. Conclusions: In contrast to AE in other conditions, AE in stroke seems to feature a unique cerebral pathology because it is mostly lateralized (contralateral to an infarction), is associated with a distinct brain area, may even occur without rtPA, and is far more frequent than after thrombolysis for other indications. rtPA is the major risk factor. Similar to prior studies, we identified ACEi to be another risk factor, and a diabetic autonomic instability might further increase the risk. Central pathways involving the insular and peri-insular cortex seem to play a major role in the pathophysiology of AE in stroke.

ProtocolTrial design and pilot phase results of a cluster-randomised intervention trial to improve stroke care after hospital discharge -The structured ambulatory post-stroke care program (SANO) Abstract Introduction: Previous studies showed insufficient control of cardiovascular risk factors (CVRF) and high stroke recurrence rates among ischemic stroke patients in Germany. Currently, no structured secondary prevention program exists in clinical routine. We present the trial design and pilot phase results of a complex intervention to improve stroke care after hospital discharge in Germany. Patients and methods: SANO is a cluster-randomized trial with 30 participating regions across Germany aiming to enrol 2,790 patients (drks.de, DRKS00015322). Study intervention combines both structural and patient-centred elements. Study development was based on the Medical Research Council framework for complex interventions. In 15 intervention regions, a cross-sectoral multidisciplinary network is established to enhance CVRF control as well as detection and treatment of post-stroke complications. Recommendations on CVRF are based on high-quality secondary prevention guidelines. Study physicians use motivational interviewing and agree with patients on therapeutic targets. While hospitalised, patients also receive dietary counselling and a health-passport to track their progress. During regular visits, CVRF management and potential complications are monitored. The intervention is compared to 15 regions providing usual care. The primary endpoint is the combination of recurrent stroke, myocardial infarction and death assessed 12 months after enrolment and adjudicated in a blinded manner. Results: Eighteen patients were enrolled in a pilot phase that demonstrated feasibility of patient recruitment and study procedures. Conclusion: SANO is investigating a program to reduce outcome events after ischemic stroke by implementing a complex intervention. If successful, the program may be implemented in routine care on national level in Germany.

Since the beginning oft he Covid-19 pandemic we have observed an increased incidence of transient global amnesia, possibly related to emotional stress as a trigger factor.