BackgroundFatigue affects about half of stroke survivors, but its natural history and associations are uncertain. We aimed to determine the trajectory of fatigue between 6 and 12 months after stroke, and factors associated with changes in fatigue between 6 and 12 months after stroke, in patients recruited to three large clinical trials.MethodsWe performed three large randomised, placebo-controlled trials of fluoxetine 20mg daily for six months, for stroke recovery. Short Form 36 (SF-36) vitality scores measured post-stroke fatigue at 6 and 12 months. We undertook an individual patient data meta-analysis (IPDM) to explore the proportion of patients with fatigue at 6 months (SF-36 vitality score ≤45) who moved to a 'no fatigue' category at 12 months, the proportion with 'no fatigue' at 6 months who moved to a fatigue category, and the proportion experiencing a clinically relevant improvement in fatigue (increase in SF36 vitality of 10 points) from 6 to 12 months. We performed regression analyses to identify which baseline factors and whether the mood (self-assessed combined anxiety/depression) and pain components of EuroQol 5D-5L (EQ 5D-5L) at 6 months influenced fatigue trajectory between 6 and 12 months.ResultsA total of 5907 patients were included. Fatigue (SF-36 vitality scores) was recorded at 6 and 12 months in 5025 (85%) patients. Fatigue (SF-36 vitality ≤45) at 6 months was present in 1489 (29.6%, 95%CI: 28.4 to 30.9%) participants, of whom 568 (38.1%, 95%CI: 35.7% to 40.7%) had no fatigue at 12 months. Fatigue at 12 months was present in 1474 (29.3%, 28.0 to 30.6%) participants, of whom 553 (15.6%, 95% CI 14.5% to 16.9%) had no fatigue at 6 months.Patient consent (rather than proxy consent), being able to lift arms off bed at baseline, and severe/extreme pain at 6 months were independently associated with persistence of fatigue through to 12 months, whereas stroke type (embolic or small vessel disease vs haemorrhagic) at baseline and self-assessed slight anxiety/depression at 6 months were associated with fatigue resolution by 12 months.Among those without fatigue at 6 months, Asians (compared to whites), and those reporting moderate or severe anxiety/depression problems were less likely to have fatigue at 12 months.ConclusionMore than a third of patients with fatigue at 6 months experienced a clinically relevant reduction in fatigue between 6 and 12 months, whereas one sixth of patients without fatigue at 6 months developed fatigue at 12 months. Although the individual regression analyses identified statistically significant associations between some independent variables and fatigue at 12 months, there was no consistent pattern across the analyses. Future research should identify factors associated with the development and recovery of fatigue after stroke.

BackgroundCovert brain infarction (CBI) is a frequent incidental neuroradiological finding increasingly recognized as clinically relevant due to its association with stroke, cognitive decline, and other adverse outcomes. However, substantial uncertainty remains regarding its optimal assessment and management, and existing guidelines provide limited and heterogeneous recommendations. We aimed to develop an international expert consensus on the evaluation and management of CBI using a modified Delphi methodology.MethodsA modified Delphi process was conducted with an international, multidisciplinary panel of 21 experts from 15 countries, including neurologists, neuroradiologists, neuroepidemiologists, and geriatricians. An initial questionnaire was developed from a structured literature review and identified clinical practice gaps. The survey included 91 statements across four domains: (1) prognosis, etiology, and screening; (2) neuroimaging-based management and follow-up; (3) cardiac evaluation; and (4) pharmacological management. Two iterative rounds were conducted, with anonymized responses, controlled feedback, and structured discussion. A five-point Likert scale was used. Consensus was defined a priori as ≥70% agreement.ResultsConsensus was reached on 33/91 statements (36.3%), moderate agreement on 43/91 (47.2%), and no consensus on 15/91 (16.5%). The panel agreed that CBI is associated with increased risk of ischemic stroke, cognitive impairment, and dementia, and that risk is higher with multiple lesions. Consensus supported targeted clinical evaluation, including a cardiac workup with transthoracic echocardiography in all patients and vascular imaging in selected cases. Routine population screening and systematic post-procedural imaging were not supported. Regarding management, consensus favored optimizing vascular risk factors, particularly strict blood pressure control in hypertensive patients. There was no consensus on routine antiplatelet therapy for incidental CBI, and anticoagulation was generally not supported in the absence of cardioembolic indications. Lipid-lowering showed limited consensus regarding specific benefits for CBI-related outcomes.ConclusionThis Delphi consensus highlights substantial variability in the perceived management of CBI and identifies areas of convergence, particularly in risk stratification and control of vascular risk factors. Key uncertainties remain regarding antithrombotic strategies, lipid-lowering therapy, and long-term surveillance. These results provide a pragmatic, expert-based framework to support clinical decision-making and further highlight the need for prospective studies and randomized trials in this rapidly evolving field.

The 2017 Stroke Recovery and Rehabilitation Roundtable (SRRR) consensus statement on biomarkers identified genetic and blood biomarkers as a developmental priority for stroke recovery and rehabilitation. While progress has been made, this nascent field still lags behind other medical disciplines. Further development is critical because molecular biomarkers hold great promise to provide key insights into the neurobiological mechanisms of both spontaneous and treatment-induced stroke recovery. Such insights could lead to effective recovery biotherapeutics and help optimize the timing and delivery of therapies.MethodsA multidisciplinary taskforce of international experts with expertise in omics and stroke recovery identified and prioritized key focus areas. Consensus opinion was developed across 15 virtual meetings, 2 rounds of anonymous polling and a 2-day in-person meeting. Key recommendations were iteratively refined until full consensus was achieved by all taskforce members.ResultsOur main recommendation is that there is a critical need for large-scale, multi-center, discovery-based omics studies to identify molecular targets in stroke recovery. To help achieve this goal we suggest ways to harmonize future studies including timepoints for data collection, outcome measures, and biospecimen selection. In addition, we address the limitations of current candidate biomarkers, translational challenges, emerging technologies, biomarker response to interventions, multi-site collaboration, and ethical concerns.ConclusionsThere is a great need for collaborative efforts by the international neurorehabilitation community to collect and harmonize molecular biomarker data. The resulting discoveries will be foundational to precision neurorehabilitation and the development of recovery biotherapeutics to enhance recovery for stroke survivors.