Background and purpose Recurrent ischemic stroke (IS) or TIA is frequent with a considerable variation in incidence and mortality across populations. Current data on stroke recurrence and mortality are useful to examine trends, risk factors, and treatment effects. In this study, we calculated the incidence of recurrent IS or TIA in a hospital-based stroke population in Western Norway, investigated recurrence factors, and estimated the effect of recurrence on all-cause mortality. Methods This prospective cohort study registered recurrence and mortality among 1872 IS and TIA survivors admitted to the stroke unit at Haukeland University Hospital between July 2007 and December 2013. Recurrence and death until September 1, 2016, were identified by medical chart review. Cumulative incidences of recurrence were estimated with a competing risks Cox model. Multivariate Cox models were used to examine recurrence factors and mortality. Results During follow-up, 220 patients had 277 recurrent IS or TIAs. The cumulative recurrence rate was 5.4% at 1 year, 11.3% at 5 years, and 14.2% at the end of follow-up. Hypertension (HR = 1.65, 95% CI 1.21-2.25), prior symptomatic stroke (HR = 1.63, 95% CI 1.18-2.24), chronic infarcts on MRI (HR = 1.48, 95% CI 1.10-1.99), and age (HR 1.02/year, 95% CI 1.00-1.03) were independently associated with recurrence. A total of 668 (35.7%) patients died during follow-up. Recurrence significantly increased the all-cause mortality (HR = 2.55, 95% CI 2.04-3.18). Conclusions The risk of recurrent IS stroke or TIA was modest in our population and was associated with previously established risk factors. Recurrence more than doubled the all-cause mortality.

Alteplase is the only approved thrombolytic agent for acute ischaemic stroke. The overall benefit from alteplase is substantial, but some evidence indicates that alteplase also has negative effects on the ischaemic brain. Tenecteplase may be more effective and less harmfull than alteplase, but large randomised controlled phase 3 trials are lacking. The Norwegian Tenecteplase Stroke Trial (NOR-TEST) aims to compare efficacy and safety of tenecteplase vs. alteplase.

Background: Mesenchymal stem cells (MSCs) is an attractive candidate in regenerative research and clinical trials have assessed their therapeutic potential in different neurological conditions with disparate etiologies. In this systematic review, we aimed to assess safety and clinical effect of MSC treatment in traumatic spinal cord injury (TSCI), multiple sclerosis (MS) and ischemic stroke (IS).Methods: A systematic search was performed 2021-12-10 in MEDLINE, EMBASE, Web of Science and Cochrane where clinical studies assessing MSC treatment in TSCI, MS or IS were included. Studies without control group were excluded for efficacy analysis, but included in the safety analysis. For efficacy, AIS score, EDSS score and mRS were used as clinical endpoints and assessed in a meta-analysis using the random effects model.Findings: Of 5,548 identified records, 54 studies were included. Twenty-six studies assessed MSC treatment in TSCI, 14 in MS and nine in IS, of which seven, seven and five studies were controlled, respectively. There were seven serious adverse events (SAEs), of which four were related to the surgical procedure and included one death due to complications following the implantation of MSCs. Three SAEs were considered directly related to the MSC treatment and all these had a transient course. In TSCI, a meta-analysis showed no difference in conversion from AIS A to C and a trend toward more patients treated with MSCs improving from AIS A to B as compared to controls (p = 0.05). A subgroup analysis performed per protocol, showed more MSC treated patients improving from AIS A to C in studies including patients within 8 weeks after injury (p = 0.04). In MS and IS, there were no significant differences in clinical outcomes between MSC treated patients and controls as measured by EDSS and mRS, respectively.Interpretation: MSC-treatment is safe in patients with TSCI, MS and IS, although surgical implantation of MSC led to one fatal outcome in TSCI. There was no clear clinical benefit of MSC treatment, but this is not necessarily a proof of inefficacy due to the low number of controlled studies. Future studies assessing efficacy of MSC treatment should aim to do this in randomized, controlled studies.

In multiple sclerosis (MS), there is a great need for treatment with the ability to suppress compartmentalized inflammation within the central nervous system (CNS) and to promote remyelination and regeneration. Mesenchymal stem cells (MSCs) represent a promising therapeutic option, as they have been shown to migrate to the site of CNS injury and exert neuroprotective properties, including immunomodulation, neurotrophic factor secretion, and endogenous neural stem cell stimulation. This review summarizes the current understanding of the underlying neuroprotective mechanisms and discusses the translation of MSC transplantation and their derivatives from pre-clinical demyelinating models to clinical trials with MS patients.