Neuroinflammation in Acute Ischemic and Hemorrhagic Stroke.

PURPOSE OF REVIEW: This review aims to provide an overview of neuroinflammation in ischemic and hemorrhagic stroke, including recent findings on the mechanisms and cellular players involved in the inflammatory response to brain injury. RECENT FINDINGS: Neuroinflammation is a crucial process following acute ischemic stroke (AIS) and hemorrhagic stroke (HS). In AIS, neuroinflammation is initiated within minutes of the ischemia onset and continues for several days. In HS, neuroinflammation is initiated by blood byproducts in the subarachnoid space and/or brain parenchyma. In both cases, neuroinflammation is characterized by the activation of resident immune cells, such as microglia and astrocytes, and infiltration of peripheral immune cells, leading to the release of pro-inflammatory cytokines, chemokines, and reactive oxygen species. These inflammatory mediators contribute to blood-brain barrier disruption, neuronal damage, and cerebral edema, promoting neuronal apoptosis and impairing neuroplasticity, ultimately exacerbating the neurologic deficit. However, neuroinflammation can also have beneficial effects by clearing cellular debris and promoting tissue repair. The role of neuroinflammation in AIS and ICH is complex and multifaceted, and further research is necessary to develop effective therapies that target this process. Intracerebral hemorrhage (ICH) will be the HS subtype addressed in this review. Neuroinflammation is a significant contributor to brain tissue damage following AIS and HS. Understanding the mechanisms and cellular players involved in neuroinflammation is essential for developing effective therapies to reduce secondary injury and improve stroke outcomes. Recent findings have provided new insights into the pathophysiology of neuroinflammation, highlighting the potential for targeting specific cytokines, chemokines, and glial cells as therapeutic strategies.

Household income is associated with functional outcomes in a multi-institutional cohort of patients with ischemic stroke and COVID-19.

OBJECTIVES: The COVID-19 pandemic has heightened awareness of health disparities associated with socioeconomic status (SES) across the United States. We examined whether household income is associated with functional outcomes after stroke and COVID-19. MATERIALS AND METHODS: This was a multi-institutional, retrospective cohort study of consecutively hospitalized patients with SARS-CoV-2 and radiographically confirmed stroke presenting from March through November 2020 to any of five comprehensive stroke centers in metropolitan Chicago, Illinois, USA. Zip-code-derived household income was dichotomized at the Chicago median. Logistic regression was used to examine the relationship between household income and good functional outcome (modified Rankin Scale 0-3 at discharge, after ischemic stroke). RESULTS: Across five hospitals, 159 patients were included. Black patients comprised 48.1%, White patients 38.6%, and Hispanic patients 27.7%. Median household income was $46,938 [IQR: $32,460-63,219]. Ischemic stroke occurred in 115 (72.3%) patients (median NIHSS 7, IQR: 0.5-18.5) and hemorrhagic stroke in 37 (23.7%). When controlling for age, sex, severe COVID-19, and NIHSS, patients with ischemic stroke and household income above the Chicago median were more likely to have a good functional outcome at discharge (OR 7.53, 95% CI 1.61 - 45.73; P=0.016). Race/ethnicity were not included in final adjusted models given collinearity with income. CONCLUSIONS: In this multi-institutional study of hospitalized patients with stroke, those residing in higher SES zip codes were more likely to have better functional outcomes, despite controlling for stroke severity and COVID-19 severity. This suggests that area-based SES factors may play a role in outcomes from stroke and COVID-19.

Recent advances in the management of transient ischemic attacks.

Transient ischemic attack (TIA) constitutes an important clinical condition, indicating the presence of considerable risk for a subsequent ischemic stroke. Its prompt diagnosis and management have the potential for reducing the risk of neurologic disability, highlighting the critical need to prioritize the care of patients with TIA. The risk of ischemic stroke following a TIA is directly related to its etiopathogenesis, and recognizable causes are commonly categorized within one of three domains: cerebrovascular pathology, cardiac dysfunction, and hematologic disorders. Therefore, the clinical approach to patients suspected of having suffered a TIA demands a comprehensive evaluation, including testing of possible etiologic conditions in all three of these domains, best carried out in an expedited fashion since the stroke risk is greatest in the hours and days that follow the index event. The present is a review of the existing literature addressing the diagnosis, evaluation, prioritization, and management strategies available to clinicians who provide care to patients with TIA.

Mechanical Thrombectomy vs Bridging Therapy for Anterior Circulation Large Vessel Occlusion Stroke: Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVES: Current guidelines recommend the use of mechanical thrombectomy (MT) plus IV thrombolysis (aka bridging therapy [BT]) for patients with anterior circulation large vessel occlusion (LVO) stroke. However, clinical equipoise exists in relation to the use of BT vs MT alone. Our objective is to compare the efficacy and safety of BT and MT for anterior circulation LVO. METHODS: A systematic search of biomedical literature databases was performed from inception to October 29, 2021, to identify prospective and retrospective studies comparing the rates for functional independence (modified Rankin Scale score 0-2) and mortality at 90 days, symptomatic intracranial hemorrhage (sICH), and successful recanalization rates for MT and BT. Effect size was represented by odds ratio (OR), and analysis was done with random-effects meta-analysis. Heterogeneity was assessed by I 2 and Cochrane Q statistics. RESULTS: Overall, 41 studies with 14,885 patients were included. Mean ± SD age was 69 ± 11 years for BT and 70 ± 11 years for MT. All studies used alteplase as the thrombolytic agent. The BT group had 29% higher odds for functional independence (OR 1.29, 95% CI 1.16-1.44, I 2 = 42%), 25% higher odds of successful reperfusion (OR 1.25, 95% CI 1.08-1.44, I 2 = 42%), and 31% decrease in odds for mortality (OR 0.69, 95% CI 0.60-0.80, I 2 = 47%) compared with MT. sICH prevalence was similar between groups (OR 1.10, 95% CI 0.95-1.28, I 2 = 0%). Six of the studies were randomized controlled trials (RCTs) with intention-to-treat analysis done in patients presenting directly to MT-capable centers. When analysis was restricted to these 6 RCTs (n = 2,333), no differences were observed in functional independence (OR 1.08, 95% CI 0.91-1.27, I 2 = 0%), sICH (OR 1.37, 95% CI 0.95-1.97, I 2 = 0%), or mortality (OR 0.93, 95% CI 0.74-1.16, I 2 = 0%) between groups. However, successful reperfusion favored the BT group (OR 1.35, 95% CI 1.06-1.73, I 2 = 0%). DISCUSSION: The odds for functional independence, successful reperfusion, and mortality for the entire dataset favored the use of BT over MT (medium heterogeneity and low quality of evidence). When analysis was restricted to RCTs, both treatments had similar functional and safety outcomes (no heterogeneity), but recanalization rates favored the BT group (no heterogeneity). Because these findings may differ in patients who present to non-MT-capable centers or with the use of other thrombolytic agents, further RCTs are needed.

Stroke Prevention in Cervical Artery Dissection.

PURPOSE OF REVIEW: Cervical artery dissection (CAD) is rare, yet it is a common cause of stroke in young and middle-aged adults. Historically, some senior clinicians favored anticoagulation in the prevention of stroke due to CAD. Choosing the optimal antithrombotic treatment with either antiplatelet (AP) or anticoagulant (AC) medications remains a challenge. This paper will review the clinical features and imaging of CAD, and the acute treatment and prevention of stroke due to CAD. RECENT FINDINGS: Until 2015, there were no prospective randomized trials in the optimal antithrombotic management of CAD. The Cervical Artery Dissection in Stroke Study (CADISS) trial found that treatment with AC did not lower the risk of subsequent stroke or death at 3 months when compared to AP agents. This led to a paradigm shift in national guidelines. In 2021, The Biomarkers and Antithrombotic Treatment in of Cervical Artery Dissection (TREAT-CAD) trial however did not confirm the non-inferiority of AP therapy in stroke prevention due to CAD. The optimal antithrombotic management for stroke prevention in CAD remains uncertain, while the superiority of anticoagulation has not been established, nor has the non-inferiority of AP agents. The future direction of research should consider early preventative treatment, dual treatment with AP agents, direct oral AC medications, and aggregation of data from existing randomized trials.

The Neurological Manifestations of Post-Acute Sequelae of SARS-CoV-2 infection.

PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global health challenge. This review aims to summarize the incidence, risk factors, possible pathophysiology, and proposed management of neurological manifestations of post-acute sequelae of SARS-CoV-2 infection (PASC) or neuro-PASC based on the published literature. RECENT FINDINGS: The National Institutes of Health has noted that PASC is a multi-organ disorder ranging from mild symptoms to an incapacitating state that can last for weeks or longer following recovery from initial infection with SARS-CoV-2. Various pathophysiological mechanisms have been proposed as the culprit for the development of PASC. These include, but are not limited to, direct or indirect invasion of the virus into the brain, immune dysregulation, hormonal disturbances, elevated cytokine levels due to immune reaction leading to chronic inflammation, direct tissue damage to other organs, and persistent low-grade infection. A multidisciplinary approach for the treatment of neuro-PASC will be required to diagnose and address these symptoms. Tailored rehabilitation and novel cognitive therapy protocols are as important as pharmacological treatments to treat neuro-PASC effectively. With recognizing the growing numbers of COVID-19 patients suffering from neuro-PASC, there is an urgent need to identify affected individuals early to provide the most appropriate and efficient treatments. Awareness among the general population and health care professionals about PASC is rising, and more efforts are needed to understand and treat this new emerging challenge. In this review, we summarize the relevant scientific literature about neuro-PASC.

Global Impact of COVID-19 on Stroke Care and IV Thrombolysis.

OBJECTIVE: To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods. METHODS: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. RESULTS: There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95% confidence interval [CI] -11.7 to -11.3, p < 0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95% CI -13.8 to -12.7, p < 0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95% CI -13.7 to -10.3, p = 0.001). Recovery of stroke hospitalization volume (9.5%, 95% CI 9.2-9.8, p < 0.0001) was noted over the 2 later (May, June) vs the 2 earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was noted in 3.3% (1,722/52,026) of all stroke admissions. CONCLUSIONS: The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID-19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months.

Peripheral Nervous System Manifestations Associated with COVID-19.

PURPOSE OF REVIEW: The present review discusses the peripheral nervous system (PNS) manifestations associated with coronavirus disease 2019 (COVID-19). RECENT FINDINGS: Nerve pain and skeletal muscle injury, Guillain-Barré syndrome, cranial polyneuritis, neuromuscular junction disorders, neuro-ophthalmological disorders, neurosensory hearing loss, and dysautonomia have been reported as PNS manifestations in patients with COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19. COVID-19 has shown syndromic complexity. Not only does SARS-CoV-2 affect the central nervous system but also it involves the PNS. The PNS involvement may be due to dysregulation of the immune system attributable to COVID-19. Here we review the broad spectrum of PNS involvement of COVID-19.

Treatment challenges in idiopathic extracranial ICA vasospasm case report and review of the literature.

Idiopathic extracranial internal carotid artery (ICA) vasospasm is a rare pathological phenomenon that may lead to stroke in young patients. We report a case of an 18 year-old female with recurrent extracranial ICA vasospasm since age thirteen. We summarize published data related to this condition including all twenty-three reported cases of extracranial ICA vasospasm. We describe the various proposed pathophysiological mechanisms underlying this disorder. Various treatment modalities have been attempted but there is no known long-term effective treatment.

Correction to: Central Nervous System Manifestations Associated with COVID-19.

The original version contained incorrect formatting of Dr. Napolis. His first name should be Mario and his last name should be Di Napoli.

Stroke Care Trends During COVID-19 Pandemic in Zanjan Province, Iran. From the CASCADE Initiative: Statistical Analysis Plan and Preliminary Results.

BACKGROUND: The emergence of the COVID-19 pandemic has significantly impacted global healthcare systems and this may affect stroke care and outcomes. This study examines the changes in stroke epidemiology and care during the COVID-19 pandemic in Zanjan Province, Iran. METHODS: This study is part of the CASCADE international initiative. From February 18, 2019, to July 18, 2020, we followed ischemic and hemorrhagic stroke hospitalization rates and outcomes in Valiasr Hospital, Zanjan, Iran. We used a Bayesian hierarchical model and an interrupted time series analysis (ITS) to identify changes in stroke hospitalization rate, baseline stroke severity [measured by the National Institutes of Health Stroke Scale (NIHSS)], disability [measured by the modified Rankin Scale (mRS)], presentation time (last seen normal to hospital presentation), thrombolytic therapy rate, median door-to-needle time, length of hospital stay, and in-hospital mortality. We compared in-hospital mortality between study periods using Cox-regression model. RESULTS: During the study period, 1,026 stroke patients were hospitalized. Stroke hospitalization rates per 100,000 population decreased from 68.09 before the pandemic to 44.50 during the pandemic, with a significant decline in both Bayesian [Beta: -1.034; Standard Error (SE): 0.22, 95% CrI: -1.48, -0.59] and ITS analysis (estimate: -1.03, SE = 0.24, p < 0.0001). Furthermore, we observed lower admission rates for patients with mild (NIHSS < 5) ischemic stroke (p < 0.0001). Although, the presentation time and door-to-needle time did not change during the pandemic, a lower proportion of patients received thrombolysis (-10.1%; p = 0.004). We did not see significant changes in admission rate to the stroke unit and in-hospital mortality rate; however, disability at discharge increased (p < 0.0001). CONCLUSION: In Zanjan, Iran, the COVID-19 pandemic has significantly impacted stroke outcomes and altered the delivery of stroke care. Observed lower admission rates for milder stroke may possibly be due to fear of exposure related to COVID-19. The decrease in patients treated with thrombolysis and the increased disability at discharge may indicate changes in the delivery of stroke care and increased pressure on existing stroke acute and subacute services. The results of this research will contribute to a similar analysis of the larger CASCADE dataset in order to confirm findings at a global scale and improve measures to ensure the best quality of care for stroke patients during the COVID-19 pandemic.

Central Nervous System Manifestations Associated with COVID-19.

PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19) has become a global health crisis of our time. The disease arises from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that binds to angiotensin-converting enzyme 2 (ACE2) receptors on host cells for its internalization. COVID-19 has a wide range of respiratory symptoms from mild to severe and affects several other organs, increasing the complexity of the treatment. There is accumulating evidence to suggest that SARS-CoV-2 can target the nervous system. In this review, we provide an account of the COVID-19 central nervous system (CNS) manifestations. RECENT FINDINGS: A broad spectrum of the CNS manifestations including headache, impaired consciousness, delirium, loss of smell and taste, encephalitis, seizures, strokes, myelitis, acute disseminated encephalomyelitis, neurogenic respiratory failure, encephalopathy, silent hypoxemia, generalized myoclonus, neuroleptic malignant syndrome and Kawasaki syndrome has been reported in patients with COVID-19. CNS manifestations associated with COVID-19 should be considered in clinical practice. There is a need for modification of current protocols and standing orders to provide better care for COVID-19 patients presenting with neurological symptoms.

Blood Pressure Variability: A New Predicting Factor for Clinical Outcomes of Intracerebral Hemorrhage.

Spontaneous primary intracerebral hemorrhage (ICH) is a stroke subtype associated with the highest mortality rate. High blood pressure (BP) is the most common cause of non-lobar ICH. Recent clinical trials have been inconclusive regarding the efficacy of aggressive BP lowering to improve ICH outcome. The association between high BP and ICH prognosis is rather complex and parameters other than absolute BP levels may be involved. In this regard, there is accruing evidence that BP variability (BPV) plays a major role in ICH outcome. Different BPV indices have been used to predict hematoma growth, neurological deterioration, and functional recovery. This review highlights the available evidence about the relationship between BPV and clinical outcomes among patients. We identified standard deviation (SD), residual SD, coefficient of variation, mean absolute change, average real variability, successive variation, spectral analysis using Fourier analysis, and functional successive variation (FSV) as indices to assess BPV. Most studies have demonstrated the association of BPV with ICH outcome, suggesting a need to monitor and control BP fluctuations in the routine clinical care of ICH patients. When large inter-subject variability exists, FSV is a viable alternative quantification of BPV as its computation is less sensitive to differences in the patient-specific observation schedules for BP than that of traditional indices.

Tenecteplase for Acute Ischemic Stroke: Current Evidence and Practical Considerations.

Tenecteplase offers pharmacological advantages over alteplase, and growing evidence supports its consideration for the treatment of patients with acute ischemic stroke. Its ease of administration as a single bolus makes it a preferable agent for patients who need to be urgently transported to a comprehensive stroke center for endovascular therapy (drip and ship) and for patients first evaluated at comprehensive stroke centers who are eligible for endovascular intervention (combined intravenous and endovascular approach). Recent randomized controlled trials indicated that the efficacy of tenecteplase may be similar to that of alteplase in patients with mild strokes and that it is superior to alteplase for patients with more severe strokes from a large vessel occlusion. Cumulative evidence currently favors the use of the 0.25 mg/kg dose. While tenecteplase has not been approved by regulatory agencies in the USA or the EU for the treatment of acute ischemic stroke, ongoing trials and additional clinical experience from countries where it is already being used in practice will likely clarify the role of tenecteplase for the acute management of ischemic stroke in the near future.