The approach to reperfusion therapies in stroke patients is rapidly evolving, but there is still no explanation why a substantial proportion of patients have a poor clinical prognosis despite successful flow restoration. This issue of futile recanalization is explained here by three clinical cases, which, despite complete recanalization, have very different outcomes. Preclinical research is particularly suited to characterize the highly dynamic changes in acute ischemic stroke and identify potential treatment targets useful for clinical translation. This review surveys the efforts taken so far to achieve mouse models capable of investigating the neurovascular underpinnings of futile recanalization. We highlight the translational potential of targeting tissue reperfusion in fully recanalized mouse models and of investigating the underlying pathophysiological mechanisms from subcellular to tissue scale. We suggest that stroke preclinical research should increasingly drive forward a continuous and circular dialogue with clinical research. When the preclinical and the clinical stroke research are consistent, translational success will follow.

Cerebral edema (CE) and hemorrhagic transformation (HT) are frequent and unpredictable events in patients with acute ischemic stroke (AIS), even when an effective vessel recanalization has been achieved. These complications, related to blood-brain barrier (BBB) disruption, remain difficult to prevent or treat and may offset the beneficial effect of recanalization, and lead to poor outcomes. The aim of this translational study is to evaluate the association of circulating and imaging biomarkers with subsequent CE and HT in stroke patients with the dual purpose of investigating possible predictors as well as molecular dynamics underpinning those events and functional outcomes. Concurrently, the preclinical study will develop a new mouse model of middle cerebral artery (MCA) occlusion and recanalization to explore BBB alterations and their potentially harmful effects on tissue. The clinical section of the study is based on a single-center observational design enrolling consecutive patients with AIS in the anterior circulation territory, treated with recanalization therapies from October 1, 2015 to May 31, 2020. The study will employ an innovative evaluation of routine CT scans: in fact, we will assess and quantify the presence of CE and HT after stroke in CT scans at 24 h, through the quantification of anatomical distortion (AD), a measure of CE and HT. We will investigate the relationship of AD and several blood biomarkers of inflammation and extracellular matrix, with functional outcomes at 3 months. In parallel, we will employ a newly developed mouse model of stroke and recanalization, to investigate the emergence of BBB changes 24 h after the stroke onset. The close interaction between clinical and preclinical research can enhance our understanding of findings from each branch of research, enabling a deeper interpretation of the underlying mechanisms of reperfusion injury following recanalization treatment for AIS.

Unilateral spatial neglect (USN) is a neuropsychological syndrome characterized by a reduced awareness of, and attention toward, stimuli located in the contralesional space. The left side of the space is most frequently affected, due to the higher incidence of the disorder following right-hemisphere lesions, particularly within the territory of the right middle cerebral artery and, less commonly, the right anterior cerebral artery. Although USN can also occur following left-hemisphere damage, it is typically less severe and tends to resolve more quickly. USN is a common consequence of acquired brain injury, especially of vascular origin, and significantly impairs a patient’s functional abilities and quality of life. Its high incidence in the acute phase after stroke, together with its potential persistence into the chronic stage, makes early diagnosis and timely rehabilitation essential. In this narrative review, we provide an overview of current assessment tools and rehabilitation approaches for post-stroke USN, with a focus also on recent advances and emerging therapeutic strategies. To illustrate diagnostic and therapeutic decision making, a representative case of a patient admitted to a Stroke Unit is reported, illustrating the application of assessment methods in a real-world setting. The aim of this review is to offer clinicians practical tools and evidence-based strategies to support a more effective and individualized management of patients affected by this complex and disabling condition.

Objectives: Atrial fibrillation (AF) is associated with high risk of ischaemic stroke (IS). Oral anticoagulant therapy (OAT) is the standard of care for stroke prevention, even though its management remains challenging in clinical practice. An emerging problem is embolic events occurring on adequately conducted OAT, the so-called resistant stroke (RS). We aimed to describe pre-stroke prevention therapy, management on hospital discharge, and therapy at follow-up in all patients with AF hospitalized for IS and in the RS subgroup. Methods: We conducted a retrospective monocentric study of patients with known AF hospitalized for an IS. A subgroup with RS was identified. We recorded information on prevention therapy at home, recommended therapy at discharge, and data on outcome and prevention therapy at follow-up. Results: We identified 226 patients, 61% females, median age 84.04 years. Preventive therapy at home was performed in 121 (53.5%) (119 OAT and 2 Left Atrial Appendage Occlusion). At hospital discharge OAT was prescribed to 78.2% of patients. RS was diagnosed in 33 patients whose management at discharge was: same OAT in 12, shift to another Direct Oral Anticoauglant (DOAC) in 5, from DOAC to Vitamin K Antagonist (VKA) and vice versa in 11, non-specified OAT in 4. At final, follow-up of 208 days (range 85–443) 23.3% (34/146) did not assume OAT. OAT was significantly associated with survival probability (p < 0.001). Conclusions: Our findings confirm a scarce adoption of guidelines for AF-related embolic events, even in the absence of absolute contraindication to OAT. RS remains an underexplored clinical entity with empirical management, highlighting the need for targeted research and tailored therapeutic strategies.