Post-stroke cognitive impairment is a common and disabling condition with few effective therapeutic options. After stroke, neural reorganization and other neuroplastic processes occur in response to ischemic injury, which can result in clinical improvement through spontaneous recovery. Neuromodulation through transcranial direct current stimulation (tDCS) is a promising intervention to augment underlying neuroplasticity in order to improve cognitive function. This form of neuromodulation leverages mechanisms of neuroplasticity post-stroke to optimize neural reorganization and improve function. In this review, we summarize the current state of cognitive neurorehabilitation post-stroke, the practical features of tDCS, its uses in stroke-related cognitive impairment across cognitive domains, and special considerations for the use of tDCS in the post-stroke patient population.

Transient ischemic attack (TIA) is traditionally viewed as a self-resolving episode of neurological change without persistent impairments and without evidence of acute brain injury on neuroimaging. However, emerging evidence suggests that TIA may be associated with lingering cognitive dysfunction. Cognitive impairment is a prevalent and disabling sequela of ischemic stroke, but the clinical relevance of this phenomenon after TIA is less commonly recognized. We performed a literature search of observational studies of cognitive function after TIA. There is a consistent body of literature suggesting that rates of cognitive impairment following TIA are higher than healthy controls, but the studies included here are limited by heterogeneity in design and analysis methods. We go on to summarize recent literature on proposed pathophysiological mechanisms underlying the development of cognitive impairment following TIA and finally suggest future directions for further research in this field.

Embolic stroke of undetermined source (ESUS) can be attributed to a variety of potential embolic sources, with differential response to anticoagulation. A multicenter, retrospective observational cohort study (27 sites) of consecutive adult patients with acute ischemic stroke due to ESUS (admitted 2015-2024) was conducted. The aim was to compare outcomes after antiplatelet(s) vs anticoagulant (±antiplatelet) treatment in patients with ESUS across potential embolic sources. The time from admission to the primary composite outcome of recurrent stroke, major bleeding, or death was assessed using adjusted Cox proportional hazard regression (clustered by site) and propensity score (PS) matching with (1) inverse probability of treatment weighting (IPTW) and (2) 10:1 nearest-neighbor matching with replacement, adjusting for age, stroke severity, and potential embolic sources (e.g., left ventricular injury and patent foramen ovale). Recurrent stroke, major bleeding, and death were also assessed as secondary outcomes, with stratification by potential embolic sources. Of the 2,328 included patients (n = 230 treated with anticoagulation), the median age was 65 years (interquartile range [IQR] 54-75), 50% were female, and the median NIH Stroke Scale score was 4 (IQR 2-11). Compared with patients treated using antiplatelet(s) therapies, those treated with anticoagulants were not at a lower risk of the primary outcome in the adjusted Cox model (adjusted hazard ratio [aHR] 1.00, 95% CI 0.69-1.45), adjusted IPTW regression model (aHR 1.15, 95% CI 0.79-1.66), or 10:1 PS-matched regression model (aHR 1.00, 95% CI 0.70-1.44). In patients with left ventricular injury, anticoagulation was associated with a lower rate of the primary outcome (aHR 0.35, 95% CI 0.16-0.77; p-interaction <0.01) and trended toward a lower rate of recurrent ischemic stroke (aHR 0.22, 95% CI 0.05-1.08; p-interaction = 0.04) when compared with patients treated with antiplatelet(s). These real-world data validate randomized trial results in ESUS, which reported no net benefit of anticoagulation over antiplatelet therapy. These data suggest possible benefit of anticoagulation in patients with left ventricular injury, as in previous cohort studies, although the findings are limited by the small number of patients treated with anticoagulation. Future trials should evaluate treatment differences in this subgroup. Cardiac Abnormalities in Stroke Prevention and Risk of Recurrence; registration ID: NCT06398366. Registered on May 3, 2024. This study provides Class III evidence that in patients with ESUS, anticoagulation was not superior to antiplatelet therapy in reducing the risk of recurrent stroke, bleeding, or death.

BACKGROUND: Intracranial atherosclerosis (ICAS) is associated with an increased risk of early recurrent ischemic stroke. We evaluated whether biomarkers of impaired distal perfusion—specifically, anterior circulation borderzone infarct, and hypoperfusion mismatch volume—were associated with recurrent ischemic stroke within 90 days. METHODS: The BIORISK ICAS (Biomarkers and Recurrence Risk in Symptomatic Intracranial Atherosclerosis) is a multicenter retrospective international study (35 sites) that included hospitalized patients with symptomatic ICAS (50%–99% luminal stenosis of the intracranial vertebral, basilar, distal internal carotid, or proximal middle cerebral artery) from January 2019 to June 2024. The primary outcome was recurrent ischemic stroke in the territory of the symptomatic artery within 90 days. In the primary analysis, the exposure was an acute anterior circulation borderzone infarct. In secondary analysis of the subset with presentation within 72 hours of last known normal and perfusion imaging completed, the exposure of interest was prespecified as hypoperfusion mismatch volume at T _max (time to maximum) threshold of 6 seconds, dichotomized at the Youden index. We performed multivariable Cox regression to test associations between exposure variables and the outcome, adjusting for clinically relevant variables and those associated with the outcome ( P <0.1). RESULTS: Of 2050 patients with symptomatic ICAS, 1737 (84.7%) presented within 72 hours of symptom onset, among whom 509 (29.3%) underwent perfusion imaging. The primary analysis included 1891 patients; 174 (9.2%) patients had recurrent ischemic stroke in the symptomatic arterial territory. In adjusted Cox regression models, there was an association between anterior circulation borderzone infarct and recurrent ischemic stroke at 90 days (adjusted hazard ratio, 1.40 [95% CI, 1.02–1.93]). In the perfusion imaging analysis, hypoperfusion mismatch of ≥10 mL was associated with recurrent ischemic stroke (adjusted hazard ratio, 1.83 [95% CI, 1.03–3.28]). CONCLUSIONS: Biomarkers of impaired distal perfusion, anterior circulation borderzone infarct, and hypoperfusion mismatch were associated with increased risk of recurrent ischemic stroke. These findings support the use of perfusion imaging in ICAS as well as future trials investigating early reperfusion in high-risk patients with ICAS.

Risk of readmission after stroke differs by stroke (sub)type and etiology, with higher risks reported for hemorrhagic stroke and cardioembolic stroke. We examined the risk and cause of first readmission by stroke subtype over the years post incident stroke. Atherosclerosis Risk in Communities (ARIC) study participants (n = 1,412) with first-ever stroke were followed up for all-cause readmission after incident stroke. Risk of first readmission was examined by stroke subtypes (cardioembolic, thrombotic/lacunar, and hemorrhagic [intracerebral and subarachnoid]) using Cox and Fine-Gray proportional hazards models, adjusting for sociodemographic and cardiometabolic risk factors. Among 1,412 participants (mean [SD] age 72.4 [9.3] years, 52.1% women, 35.3% Black), 1,143 hospitalizations occurred over 41,849 person-months. Overall, 81% of participants were hospitalized over a maximum of 26.6 years of follow-up (83% of participants with thrombotic/lacunar stroke, 77% of participants with cardioembolic stroke, and 78% of participants with hemorrhagic stroke). Primary cardiovascular and cerebrovascular diagnoses were reported for half of readmissions. Over the entire follow-up period, compared with cardioembolic stroke, readmission risk was lower for thrombotic/lacunar stroke (hazard ratio [HR] 0.82, 95% CI 0.71-0.95) and hemorrhagic stroke (HR 0.74, 95% CI 0.58-0.93) in adjusted Cox proportional hazards models. By contrast, there was no statistically significant difference among subtypes when adjusting for atrial fibrillation and competing risk of death. Compared with cardioembolic stroke, thrombotic/lacunar stroke was associated with lower readmission risk within 1 month (HR 0.66, 95% CI 0.46-0.93) and during 1 month-1 year (HR 0.78, 95% CI 0.62-0.97), and hemorrhagic stroke was associated with lower risk during 1 month-1 year (HR 0.60, 95% CI 0.41-0.87). There was no significant difference between subtypes in readmission risk during later periods. Over 26 years of follow-up, 81% of stroke participants experienced a readmission. Cardiovascular and cerebrovascular diagnoses at readmission were most common across stroke subtypes. Though cardioembolic stroke has previously been reported to confer higher risk of readmission, in this study, the readmission risk was not statistically significantly different between stroke subtypes or over different periods when accounting for the competing risk of death.