This review explores the therapeutic potential of dual adenosine A1 and A3 receptor (A1R/A3R) agonism as a neuroprotective treatment for acute ischemic stroke (AIS) and traumatic brain injury (TBI). Current AIS treatments, tissue plasminogen activator and mechanical thrombectomy, are limited by narrow therapeutic windows and strict eligibility criteria. In contrast, TBI management remains primarily supportive, with no Food and Drug Administration-approved therapies targeting the underlying molecular pathology. Dual A1R/A3R agonists offer a new approach by modulating injury pathways at the cellular level, potentially serving as an adjunct or alternative to existing therapeutic options. A1R and A3R are G protein-coupled receptors that control neuroinflammation, excitotoxicity, and metabolic balance. Preclinical studies using rodent and non-human primate models of AIS and TBI have shown that dual A1R/A3R agonists reduce infarct size, slow lesion growth, preserve penumbral tissue, and enhance neurological recovery. These effects are mediated through astrocyte activation, support of mitochondrial function, and suppression of pro-inflammatory cytokines. The neuroprotective effects follow a U‑shaped dose–response pattern, where only intermediate doses provide benefit, whereas lower and higher doses are less effective. Compared to monotherapies, A1R/A3R agonists activate multiple overlapping pathways, including neurotransmitter regulation, apoptosis control, and blood-brain barrier function. Dual A1R/A3R agonists are a promising and adaptable neuroprotective strategy for both AIS and TBI. Their wide-ranging mechanism offers benefits beyond current revascularization options, especially for patients ineligible for tPA or thrombectomy. Early-phase data indicate strong translational potential, and ongoing trials will determine whether these results translate into improved clinical outcomes. Given the urgent need for effective neuroprotectants, A1R/A3R agonists could become an essential component of neurocritical care. AST-004 has recently advanced into a Phase II clinical evaluation, with ongoing assessments of its safety and effectiveness in humans.

Background/Objectives: The COVID-19 pandemic impacted healthcare systems globally, disrupting the management and treatment of acute ischemic stroke (AIS). Understanding how AIS admissions, treatments, and outcomes were affected is critical for improving stroke care in future crises. The objective of this work was to assess the COVID-19 pandemic's impact on AIS admissions, treatment patterns, complications, and patient outcomes in the U.S. from 2016 to 2021, focusing on differences between pre-pandemic (2016-2019) and peri-pandemic (2020-2021) periods. Methods: This is a retrospective cohort study using the National Inpatient Sample (NIS) database, analyzing weighted discharge records of AIS patients over six years. Data encompass U.S. hospitals, including urban, rural, teaching, and non-teaching facilities. The study included AIS patients aged 18 and older (N = 3,154,154). The cohort's mean age was 70.0 years, with an average hospital stay of 5.1 days and an adjusted mean cost of $16,765. Men comprised 50.5% of the cohort. We analyzed temporal trends in AIS hospitalizations from 2016 to 2021, comparing pre- and peri-COVID-19 periods. The primary outcome was the AIS admissions trend over time, with secondary outcomes including reperfusion therapy utilization, intubation rates, discharge disposition, and complications. Trends in risk factors and NIH Stroke Scale (NIHSS) severity were also evaluated. Results: AIS admissions rose from 507,920 in 2016 to 535,694 in 2021. Age and sex distribution shifted, with a growing proportion of male AIS cases (from 49.8% to 51.4%) and a decrease in mean age from 70.3 to 69.7 years. Although not statistically significant, White patients were the majority (68.0%), though their proportion declined as Black, Hispanic, and Asian/Pacific Islander cases increased. Reperfusion therapy, especially mechanical thrombectomy, rose from 2.2% to 5.6% over the study period. Intubation rates increased from 4.8% pre-COVID-19 to 5.5% peri-COVID, with higher rates among COVID-positive patients. NIHSS severity declined over time, with severe strokes (NIHSS ≥ 16) decreasing from 14.5% in 2017 to 12.6% in 2021. Conclusions: The COVID-19 pandemic brought significant shifts in AIS patterns, with younger, more diverse patients, increased reperfusion therapy use, and rising complication rates. These changes underscore the importance of resilient healthcare strategies and resource allocation to maintain stroke care amid future public health emergencies.

A deeper understanding of the communication network between the gut microbiome and the central nervous system, termed the gut-brain axis (GBA), has revealed new potential targets for intervention to prevent the development of neurodegenerative disease associated with tramatic brain injury (TBI). This review aims to comprehensively examine the role of GBA post-traumatic brain injury (TBI). The GBA functions through neural, metabolic, immune, and endocrine systems, creating bidirectional signaling pathways that modulate brain and gastrointestinal (GI) tract physiology. TBI perturbs these signaling pathways, producing pathophysiological feedback loops in the GBA leading to dysbiosis (i.e., a perturbed gut microbiome, impaired brain-blood barrier, impaired intestinal epithelial barrier (i.e., “leaky gut”), and a maladaptive, systemic inflammatory response. Damage to the CNS associated with TBI leads to GI dysmotility, which promotes small intestinal bacterial overgrowth (SIBO). SIBO has been associated with the early stages of neurodegenerative conditions such as Parkinson’s and Alzheimer’s disease. Many of the bacteria associated with this overgrowth promote inflammation and, in rodent models, have been shown to compromise the structural integrity of the intestinal mucosal barrier, causing malabsorption of essential nutrients and further exacerbating dysbiosis. TBI-induced pathophysiology is strongly associated with an increased risk of neurodegenerative diseases, including Parkinson’s and Alzheimer’s diseases, which represents a significant public health burden and challenge for patients and their families. A healthy gut microbiome has been shown to promote improved recovery from TBI and prevent the development of neurodegenerative disease, as well as other chronic complications. The role of the gut microbiome in brain health post-TBI demonstrates the potential for microbiome-targeted interventions to mitigate TBI-associated comorbidities. Promising new evidence on prebiotics, probiotics, diet, and fecal microbiota transplantation may lead to new therapeutic options for improving the quality of life for patients with TBI. Still, many of these preliminary findings must be explored further in clinical settings. This review covers the current understanding of the GBA in the setting of TBI and how the gut microbiome may provide a novel therapeutic target for treatment in this patient population.

BackgroundEndovascular therapy (EVT) stands as an established and effective intervention for acute ischemic stroke in patients harboring tandem lesions (TLs). However, the optimal anesthetic strategy for EVT in TL patients remains unclear. This study aims to evaluate the impact of distinct anesthetic techniques on outcomes in acute ischemic stroke patients presenting with TLs.MethodsPatient-level data, encompassing cases from 16 diverse centers, were aggregated for individuals with anterior circulation TLs treated between January 2015 and December 2020. A stratification based on anesthetic technique was conducted to distinguish between general anesthesia (GA) and procedural sedation (PS). Multivariable logistic regression models were built to discern the association between anesthetic approach and outcomes, including the favorable functional outcome defined as 90-day modified Rankin Score (mRS) of 0–2, ordinal shift in mRS, symptomatic intracranial hemorrhage (sICH), any hemorrhage, successful recanalization (modified Thrombolysis In Cerebral Infarction (mTICI) score ≥2b), excellent recanalization (mTICI 3), first pass effect (FPE), early neurological improvement (ENI), door-to-groin and recanalization times, intrahospital mortality, and 90-day mortality.ResultsAmong 691 patients from 16 centers, 595 patients (GA 38.7%, PS 61.3%) were included in the final analysis. There were no significant differences noted in the door-to-groin time (80 (46–117.5) mins vs 54 (21–100), P=0.607) and groin to recanalization time (59 (39.5–85.5) mins vs 54 (38–81), P=0.836) among the groups. The odds of a favorable functional outcome (36.6% vs 52.6%; adjusted OR (aOR) 0.56, 95% CI 0.38 to 0.84, P=0.005) and a favorable shift in the 90-day mRS (aOR 0.71, 95% CI 0.51 to 0.99, P=0.041) were lower in the GA group. No differences were noted for sICH (3.9% vs 4.7%, P=0.38), successful recanalization (89.1% vs 86.5%, P=0.13), excellent recanalization (48.5% vs 50.3%, P=0.462), FPE (53.6% vs 63.4%, P=0.05), ENI (38.9% vs 38.8%, P=0.138), and 90-day mortality (20.3% vs 16.3%, P=0.525). An interaction was noted for favorable functional outcome between the type of anesthesia and the baseline Alberta Stroke Program Early CT Score (ASPECTS) (P=0.033), degree of internal carotid artery (ICA) stenosis (P<0.001), and ICA stenting (P<0.001), and intraparenchymal hematoma between the type of anesthesia and intravenous thrombolysis (P=0.019). In a subgroup analysis, PS showed better functional outcomes in patients with age ≤70 years, National Institutes of Health Stroke Scale (NIHSS) score <15, and acute ICA stenting.ConclusionsOur findings suggest that the preference for PS not only aligns with comparable procedural safety but is also associated with superior functional outcomes. These results prompt a re-evaluation of current anesthesia practices in EVT, urging clinicians to consider patient-specific characteristics when determining the optimal anesthetic strategy for this patient population.

Traumatic brain injury (TBI) continues to be a major cause of death and disability worldwide. Biomarkers for treatment and prognostication are needed for counseling and clinical management. In this study, we evaluated the ability of serum IL-6 to predict mortality and disability in a population whith moderate and severe TBI (msTBI). Adult patients with msTBI were included consecutively from December 2019 to August 2023. Clinical data were collected during hospital stays and functional outcome was established at 6 months using GOSE. Serum IL-6 levels were measured on day 0, day 3 and day 7 after injury. Eighty-eight patients were recruited and completed 6-month follow-up. Clinical variables associated with the 6-month adverse outcome were admission GCS (OR 0.77 95

BACKGROUND:Traumatic brain injury (TBI) continues to be a major cause of death and disability worldwide. Effective treatment options are limited, and randomized clinical data has been futile. OBJECTIVE:In this study, we assessed the efficacy of tauroursodeoxycholic acid (TUDCA) in treating TBI using a controlled cortical impact injury model in male Wistar rats. METHODS:Animals were randomized into two experimental groups: 1) TBI with sham treatment (Control, n = 12) and 2) TBI treated with intravenous infusion of 300 mg/kg TUDCA (TUDCA-treated group, n = 10) 30 min post-injury. Anxiety levels and magnetic resonance imaging studies were performed on days 1 and 7 post-injury. Animals were euthanized on day 7 for histopathological assessments. RESULTS:On days 1 and 7, we observed a smaller brain lesion volume in the TUDCA-treated group compared with the Control group and greater cytotoxic edema on day 1 in the Control group. Elevated plus maze revealed a lower anxiety index for the TUDCA-treated group on day 7. CONCLUSION:Our study showed that TBI rats treated with TUDCA at a hyperacute stage had a statistically significant reduction in lesion volume and improved levels of anxiety. However, a dose-response relationship and ideal therapeutic window still need to be determined. Future studies should consider a multiday therapy paradigm to identify the optimum intervention frequency in a mixed-gender.

BackgroundIntracranial hemorrhage (ICH) is a devastating stroke subtype with a high rate of mortality and disability. Therapeutic options available are primarily limited to supportive care and blood pressure control, whereas the surgical approach remains controversial. In this study, we explored the effects of noninvasive vagus nerve stimulation (nVNS) on hematoma volume and outcome in a rat model of collagenase-induced ICH.MethodsAdult male Wistar rats were randomized into two study groups: (1) ICH-treated (rats treated with five 2-min nVNS) and (2) ICH-control (ICH with sham nVNS). Each group received either a 0.1-U or a 0.2-U collagenase dose. After assessing neurological function, rats were euthanized at 24 h for spectrophotometric hemoglobin assay, hematoma volume measurements, and histological studies.ResultsThe ICH-treated group that received the 0.1-U collagenase dose demonstrated significantly smaller hematoma volume and improved motor function compared with the ICH-control with the same dose. Furthermore, the pooled data for the ICH-treated groups (both 0.1 U and 0.2 U of collagenase) revealed a reduction in neuronal loss in the perihematomal region in the histopathological studies. This effect was not significant for the group that received a 0.2-Ucollagenase dose.ConclusionsnVNS therapy in acute settings may provide a neuroprotective effect and limit hematoma expansion in smaller volumes, improving neurological function post-ICH.

This review examines the evolving field of neurocardiology, tracing its development from early homeostatic theories to modern understandings of the bidirectional neural networks that link the heart and brain. We propose an integrative framework to explain neuro-cardiac interactions in health and disease, with a focus on clinical applications and emerging therapies. The neuro-cardiac axis comprises hierarchical neural networks, from the intrinsic cardiac nervous system to subcortical and cortical brain regions. This structure underlies a range of clinical syndromes. Acute brain injuries can induce cardiac dysfunction via autonomic dysregulation, as seen in neurogenic stunned myocardium (NSM), while cardiac disease contributes to cerebral small vessel disease (CSVD) and cognitive decline. Cardioception—the brain’s processing of cardiac signals—is increasingly recognized as a key mediator of autonomic control and emotional experience. Clinical trials highlight the value of targeted interventions, including extended cardiac monitoring to detect occult atrial fibrillation, improved risk stratification for managing patent foramen ovale, and intensive vascular risk control for cerebrovascular protection. Growing awareness of neuro-cardiac pathways is reshaping clinical care. Understanding how brain insults provoke cardiac dysfunction via disrupted autonomic outflow is critical, particularly in NSM. Meanwhile, cardioception is gaining relevance as a therapeutic target in the regulation of emotions and the autonomic nervous system. Conversely, cardiac pathology promotes stroke, CSVD, and cognitive impairment not only through embolism but also through altered perfusion and autonomic imbalance. Comprehensive management of modifiable vascular risks confers dual protection for the heart and brain. Interdisciplinary collaboration is increasingly vital for managing disorders along the heart–brain continuum. Translating insights from neurocardiac mechanisms into precision therapies marks a new frontier. Advances in neuroimaging, artificial intelligence, and neuromodulation offer opportunities for personalized care. The ongoing development of cross-specialty training and integrated research platforms will be essential for translating scientific progress into improved outcomes in neurocardiac disorders.

OBJECTIVE The optimal technique for treating tandem lesions (TLs) with endovascular therapy is debatable. The authors evaluated the functional, safety, and procedural outcomes of different approaches in a multicenter study. METHODS Anterior circulation TL patients treated from January 2015 to December 2020 were divided on the basis of antegrade versus retrograde approach and included. The evaluated outcomes were favorable modified Rankin Scale (mRS) score (mRS score 0-2) at 3 months, ordinal shift in mRS score, successful recanalization, excellent recanalization, first-pass effect (FPE), time from groin puncture to successful recanalization, symptomatic intracranial hemorrhage (sICH), and 90-day mortality. RESULTS Among 691 patients treated at 16 centers, 286 patients (174 antegrade and 112 retrograde approach patients) with acute stenting were included in the final analysis. There were no significant differences in mRS score 0-2 at 90 days (52.2% vs 50.0%, adjusted odds ratio [aOR] 0.83, 95% CI 0.42-1.56, p = 0.54), favorable shift in 90-day mRS score (aOR 1.03, 95% CI 0.66-1.29, p = 0.11), sICH (4.0% vs 4.5%, aOR 0.64, 95% CI 0.24-1.51, p = 0.45), successful recanalization (89.4% vs 93%, aOR 0.49, 95% CI 0.19-1.28, p = 0.19), excellent recanalization (51.4% vs 58.9%, aOR 0.59, 95% CI 0.40-1.07, p = 0.09), FPE (58.3% vs 69.7%, aOR 0.62, 95% CI 0.44-1.15, p = 0.21), and mortality at 90 days (16.6% vs 14.0%, aOR 0.94, 95% CI 0.35-2.44, p = 0.81) between the groups. The median (interquartile range) groin puncture to recanalization time was significantly longer in the antegrade group (59 [43-90] minutes vs 49 [35-73] minutes, p = 0.036). CONCLUSIONS The retrograde approach was associated with faster recanalization times with a similar functional and safety profile when compared with the antegrade approach in patients with acute ischemic stroke with TL. https://thejns.org/doi/abs/10.3171/2023.10.JNS231702

Partial pressure of carbon dioxide (PaCO2) is generally known to influence outcome in patients with traumatic brain injury (TBI) at normal altitudes. Less is known about specific relationships of PaCO2 levels and clinical outcomes at high altitudes. This is a prospective single-center cohort of consecutive patients with TBI admitted to a trauma center located at 2600 m above sea level. An unfavorable outcome was defined as a Glasgow Outcome Scale-Extended (GOSE) score < 4 at the 6-month follow-up. We had a total of 81 patients with complete data, 80

This review aims to comprehensively examine the immune response following traumatic brain injury (TBI) and how its disruption can impact healing and recovery. The immune response is now considered a key element in the pathophysiology of TBI, with consequences far beyond the acute phase after injury. A delicate equilibrium is crucial for a healthy recovery. When this equilibrium is disrupted, chronic inflammation and immune imbalance can lead to detrimental effects on survival and disability. Globally, traumatic brain injury (TBI) imposes a substantial burden in terms of both years of life lost and years lived with disability. Although its epidemiology exhibits dynamic trends over time and across regions, TBI disproportionally affects the younger populations, posing psychosocial and financial challenge for communities and families. Following the initial trauma, the primary injury is succeeded by an inflammatory response, primarily orchestrated by the innate immune system. The inflammasome plays a pivotal role during this stage, catalyzing both programmed cell death pathways and the up-regulation of inflammatory cytokines and transcription factors. These events trigger the activation and differentiation of microglia, thereby intensifying the inflammatory response to a systemic level and facilitating the migration of immune cells and edema. This inflammatory response, initially originated in the brain, is monitored by our autonomic nervous system. Through the vagus nerve and adrenergic and cholinergic receptors in various peripheral lymphoid organs and immune cells, bidirectional communication and regulation between the immune and nervous systems is established.

Background Recent trials confirmed the efficacy and safety of endovascular thrombectomy in patients with low Alberta Stroke Program Early Computed Tomography Score (ASPECTS); however, evidence in tandem lesions is limited. This study evaluates endovascular thrombectomy safety and efficacy in patients with acute large‐vessel occlusion with tandem lesions, stratified by baseline ASPECTS. Methods and Results We conducted a retrospective analysis of data from 16 centers. Inclusion criteria included the following: age ≥18 years, anterior circulation tandem lesions, endovascular thrombectomy <24 hours of symptom onset, and ≥70% internal carotid artery stenosis/occlusion. Patients were categorized into low (0–5) and high (6–10) ASPECTS. Inverse probability of treatment weighting matching was used to balance the groups. Primary outcomes included the following: 90‐day modified Rankin Scale (mRS) score 0 to 2 and symptomatic intracranial hemorrhage. Secondary outcomes included the following: ordinal mRS, mRS 0 to 3, modified Thrombolysis in Cerebral Infarction ≥2b and 2c‐3, petechial hemorrhage, parenchymal hematoma (1/2), early neurologic improvement, and mortality. Of 691 patients, 44 had ASPECTS 0 to 5 and 505 had ASPECTS 6 to 10. Patients with low ASPECTS had lower odds of 90‐day mRS 0 to 2 (adjusted odds ratio [OR], 0.48; P=0.036) and higher odds of symptomatic intracranial hemorrhage (adjusted OR, 3.78; P=0.014). Additional significant differences were found in mRS shift, mRS 0 to 3, parenchymal hematoma 2, and mortality. In interaction analysis, the association between low ASPECTS and functional outcome persisted only in the internal carotid artery occlusion subgroup, with no significant interaction indicating no reason to suppose a difference between the effect of both subgroups. Conclusions Endovascular thrombectomy in patients with tandem lesions with low ASPECTS is associated with reduced odds of functional recovery and increased symptomatic intracranial hemorrhage risk, when compared with patients with high ASPECTS. However, 30% of patients with low ASPECTS achieved 90‐day functional independence, suggesting potential benefit for a nonnegligible proportion of patients.

Background and ObjectivesCurrent evidence suggests that acute carotid artery stenting (CAS) for cervical lesions is associated with better functional outcomes in patients with acute stroke with tandem lesions (TLs) treated with endovascular therapy (EVT). However, the underlying causal pathophysiologic mechanism of this relationship compared with a non-CAS strategy remains unclear. We aimed to determine whether, and to what degree, reperfusion mediates the relationship between acute CAS and functional outcome in patients with TLs. MethodsThis subanalysis stems from a multicenter retrospective cohort study across 16 stroke centers from January 2015 to December 2020. Patients with anterior circulation TLs who underwent EVT were included. Successful reperfusion was defined as a modified Thrombolysis in Cerebral Infarction scale >= 2B by the local team at each participating center. Mediation analysis was conducted to examine the potential causal pathway in which the relationship between acute CAS and functional outcome (90-day modified Rankin Scale) is mediated by successful reperfusion. ResultsA total of 570 patients were included, with a median age (interquartile range) of 68 (59-76), among whom 180 (31.6%) were female. Among these patients, 354 (62.1%) underwent acute CAS and 244 (47.4%) had a favorable functional outcome. The remaining 216 (37.9%) patients were in the non-CAS group. The CAS group had significantly higher rates of successful reperfusion (91.2% vs 85.1%; p = 0.025) and favorable functional outcomes (52% vs 29%; p = 0.003) compared with the non-CAS group. Successful reperfusion was a strong predictor of functional outcome (adjusted common odds ratio [acOR] 4.88; 95% CI 2.91-8.17; p < 0.001). Successful reperfusion partially mediated the relationship between acute CAS and functional outcome, as acute CAS remained significantly associated with functional outcome after adjustment for successful reperfusion (acOR 1.89; 95% CI 1.27-2.83; p = 0.002). Successful reperfusion explained 25% (95% CI 3%-67%) of the relationship between acute CAS and functional outcome. DiscussionIn patients with TL undergoing EVT, successful reperfusion predicted favorable functional outcomes when CAS was performed compared with non-CAS. A considerable proportion (25%) of the treatment effect of acute CAS on functional outcome was found to be mediated by improvement of successful reperfusion rates.

Introduction: Current evidence suggests that acute carotid artery stenting (CAS) for cervical lesions is associated with better functional outcomes in patients with acute stroke with tandem lesions (TLs) treated with endovascular treatment (EVT). However, a gap in understanding persists regarding the underlying causal pathophysiological mechanism of this relationship when compared to angioplasty alone. We aimed to determine whether, and to what degree, excellent reperfusion (mTICI 2c-3) mediates the relationship between acute CAS and functional outcome in patients with TLs. Methods: This sub-analysis stems from a multicenter cohort study of patients with anterior circulation TLs who underwent EVT across 16 stroke centers spanning from January 2015 to December 2020. Mediation analysis was conducted to examine the potential causal pathway in which the relationship between acute CAS and favorable functional outcome (90-day mRS 0-2) is mediated by excellent reperfusion. Results: A total of 512 patients were included, out of whom 319 (62.3%) underwent acute CAS, and 243 (47.5%) had a favorable functional outcome. Excellent reperfusion was a predictor of favorable functional outcome (adjusted OR [aOR]: 2.27, 95% CI 1.57-3.28, p =<0.001). Excellent reperfusion partially mediated the relationship between acute CAS and functional outcome ( Figure ), as acute CAS was still significantly associated with functional outcome after adjustment for excellent reperfusion (aOR: 1.56, 95% CI 1.07-2.28, p =0.022). Excellent reperfusion explained 53% (95% CI 24-87) of the relationship between acute CAS and functional outcome. Conclusions: In TL patients undergoing EVT, excellent reperfusion predicted favorable functional outcome when CAS was performed as compared to angioplasty alone. A significant proportion (53%) of the treatment effect of acute CAS on functional outcome was found to be mediated through the improvement of excellent reperfusion rates.

BACKGROUND: Tandem lesions consist of cervical internal carotid artery (ICA) stenosis or occlusion, most commonly of atherosclerosis or dissection etiology, plus a large vessel occlusion. In this study, we compare outcomes in patients with atherosclerosis versus dissection of the cervical ICA. METHODS: This multicenter retrospective cohort study includes data from tandem lesion patients who underwent endovascular treatment from 2015 to 2020. Atherosclerosis was defined as ICA stenosis/occlusion associated with a calcified lesion and dissection by the presence of a tapered or flame-shaped lesion and intramural hematoma. Primary outcome: 90-day functional independence (modified Rankin Scale score, 0-2); secondary outcomes: 90-day favorable shift in the modified Rankin Scale score, modified Thrombolysis in Cerebral Infarction score 2b-3, modified Thrombolysis in Cerebral Infarction score 2c-3, symptomatic intracranial hemorrhage, parenchymal hematoma type 2, petechial hemorrhage, distal embolization, early neurological improvement, and mortality. Analysis was performed with matching by inverse probability of treatment weighting. RESULTS: We included 526 patients (68 [59-76] years; 31% females); 11.2% presented dissection and 88.8%, atherosclerosis. Patients with dissection were younger, had lower rates of hypertension, hyperlipidemia, diabetes, and smoking history. They also exhibited higher rates of ICA occlusion, multiple stents (>1), and lower rates of carotid self-expanding stents. After matching and adjusting for covariates, there were no differences in 90-day functional independence. The rate of successful recanalization was significantly lower in the dissection group (adjusted odds ratio, 0.38 [95% CI, 0.16-0.91]; P=0.031), which also had significantly higher rates of distal emboli (adjusted odds ratio, 2.53 [95% CI, 1.15-5.55]; P=0.021). There were no differences in other outcomes. Acute ICA stenting seemed to increase the effect of atherosclerosis in successful recanalization. CONCLUSIONS: This study reveals that among patients with acute stroke with tandem lesions, cervical ICA dissection is associated with higher rates of distal embolism and lower rates of successful recanalization than atherosclerotic lesions. Using techniques to minimize the risk of distal embolism may mitigate this contrast. Further prospective randomized trials are warranted to fully understand these associations.

Background: Endovascular therapy (EVT) has been reported to be safe and effective for acute ischemic stroke (AIS) patients with tandem lesions (TLs). However, the optimal anesthetic management during EVT for TL patients is unknown. We aimed to assess the impact of anesthesia modality on clinical outcomes in AIS patients with TLs. Methods: Patient level data were pooled from 16 centers for anterior circulation TLs from 2015-2020. Patients were divided into general anesthesia (GA) and procedural sedation (PS). Multivariable logistic regression was used to assess the association of outcomes including modified Rankin Score (mRS) 0-2, ordinal shift is mRS, symptomatic intracranial hemorrhage (sICH), successful reperfusion (mTICI score ≥2b), excellent reperfusion (mTICI 3), first pass effect (FPE), early neurological recovery (ENI), door to skin puncture and reperfusion, and 90-day mortality. Results: Among 691 patients, 595 (GA:230 [38.7%] and PS:365 [61.3%]) were included in the final analysis. Patients treated with GA had lower odds of mRS 0-2 (36.6% vs. 52.5%, aOR: 0.56, 95% CI: 0.38-0.84, p =0.005) and favorable shift in 90 days mRS (aOR: 0.71, 95% CI: 0.51-0.99, p =0.041) when compared to PS. No differences were noted for sICH (3.9% vs. 4.7%, aOR: 0.66, 95% CI: 0.26-1.66, p =0.38), successful reperfusion (89.1% vs 86.5%, aOR: 1.59, CI: 0.87-2.89, p=0.13), excellent reperfusion (48.5% vs 50.3%, aOR: 0.85, CI: 0.56-1.30, p=0.462), FPE (53.6% vs 63.4%, aOR: 0.67, CI 0.45-1.0, p=0.05), ENI (38.9% vs 38.8%, aOR: 0.70, CI: 0.44-1.12, p=0.138), mortality at 90 days (20.3% vs 16.3%, aOR: 0.74, CI: 0.29-1.87, p=0.525), door to skin puncture (80 [46-117.5] mins vs 54 [21-100], p=0.607) and skin puncture to reperfusion (59 [39.5-85.5] mins vs 54 [38-81], p=0.836). Conclusions: In patients with AIS with TLs treated with EVT, GA was associated with lower odds of functional independence without a significant increased risk of sICH, mortality, or treatment delays.

INTRODUCTION:The COVID-19 pandemic has taught myriad lessons and left several questions we are yet to comprehend. Initially, the scientific community was concerned with the management of acute disease and immunization. Once the peak of the pandemic receded, it became clear that a proportion of patients were far from fully recovered. Researchers started to recognize those persisting symptoms as a new entity termed 'Long COVID,' where neurological symptoms are evident and have a major impact on quality of life. AREAS COVERED:The main purpose of this narrative review is to analyze and synthesize the current literature regarding Long COVID, its relation to the nervous system, and to explore the evidence on treatments for persistent neurological symptoms. The most common reported and observed neurologic manifestations include fatigue, cognitive impairment, pain, polyneuropathy, and neuropsychiatric disorders. A variety of pharmacologic and non-pharmacologic therapies have been evaluated and yielded mixed results. Many of them focused on immunomodulation and none currently have U.S. FDA approval. EXPERT OPINION:Challenges remain in terms of clinical characterization and prognosis of Long COVID, besides understanding its pathophysiology. Standardization of biomarkers and diagnostic criteria will allow the use of common nomenclature and data elements in the design of future clinical studies.

BACKGROUND Procedural intravenous cangrelor has been proposed as an effective platelet inhibition strategy for stenting in acute ischemic stroke. We aimed to compare the safety profile of low‐dose intravenous cangrelor versus dual oral antiplatelet therapy (DAPT) loading in patients with acute cervical tandem lesions. METHODS We retrospectively identified cases from an international multicenter cohort who underwent intraprocedural administration of intravenous cangrelor (15 μg/kg followed by an infusion of 2 μg/kg per min) or DAPT loading during acute tandem lesions intervention. Safety outcomes included rates of symptomatic intracranial hemorrhage, parenchymal hematoma type 2, petechial hemorrhage, and in‐stent thrombosis. Inverse probability of treatment weighting matching was used to reduce confounding. RESULTS From 691 patients, we included 195 patients, 30 of whom received intravenous cangrelor and 165 DAPT. The DAPT regimens were aspirin+clopidogrel (93.3%) or aspirin+ticagrelor (6.6%). After inverse probability of treatment weighting, the patients treated with cangrelor were not at greater odds of symptomatic intracranial hemorrhage (odds ratio [OR], 1.30 [95% CI, 0.09–17.3]; P=0.837), symptomatic intracranial hemorrhage–parenchymal hematoma type 2 (OR, 0.54 [95% CI, 0.05–4.98]; P=0.589), or petechial hemorrhage (OR, 1.11 [95% CI, 0.38–3.28]; P=0.836). Similarly, the rate of in‐stent thrombosis was not significantly different between the 2 groups (1.8% versus 0%; P=0.911). CONCLUSION Cangrelor at the half dose of the myocardial infarction protocol showed a similar safety profile compared with the commonly used DAPT loading protocols in patients with acute tandem lesions. Further studies with larger samples are warranted to elucidate the safety of antiplatelet therapy in tandem lesions.