Using Generative AI to Enhance Science Dissemination

Life's Essential 8 refers to key modifiable health behaviors and health factors that significantly impact stroke risk. These include: diet quality, emphasizing the Mediterranean diet and sodium reduction with potassium substitution; physical activity, promoting regular movement; weight and obesity, advocating for a healthy BMI and waist circumference; sleep, addressing sleep duration and quality; blood sugar, maintaining healthy glucose levels; blood pressure, managing hypertension; lipids, controlling cholesterol levels, and tobacco use, strongly discouraging all forms of tobacco. Managing these factors are critical for primary stroke prevention.

Diet plays a significant role in stroke prevention. The Mediterranean diet, characterized by high intake of fruits, vegetables, whole grains, and healthy fats, is beneficial. Also, reducing sodium intake, specifically through sodium substitution with potassium is recommended. While some benefits were observed with folic acid and B-complex vitamins, other supplements like long-chain fatty acids, Vitamin C, E, selenium, antioxidants, and calcium supplements have shown no benefit in reducing stroke risk. The DASH diet, while effective for lowering blood pressure, has not been specifically studied for stroke reduction, so it is not directly recommended.

Obesity, measured by BMI, waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR), is strongly associated with an increased risk of stroke. Each 5 kg/m² increase in BMI is linked to about a 10% rise in stroke risk. Increased WC and WHR also independently elevate risk. For example, for each 10-cm higher WC, there is a 10% higher risk of stroke. Screening for and managing obesity and abdominal adiposity through monitoring these measurements are crucial for primary stroke prevention.

Several medical conditions and risk factors significantly contribute to stroke risk, including: atherosclerotic and non-atherosclerotic conditions like asymptomatic carotid artery stenosis and cerebral small vessel disease (SVD); migraines; sickle cell disease; genetic stroke syndromes like CADASIL and Fabry disease; coagulation and inflammatory disorders such as antiphospholipid syndrome (APS) and rheumatoid arthritis; substance use including alcohol, cannabis, and other illicit drugs; and certain sex and gender-specific factors including pregnancy-related complications, hormonal contraception, and menopause. Additionally, lipid abnormalities like primary hypertriglyceridemia and elevated biomarkers such as C-reactive protein are also considered.

Pregnancy is associated with an increased risk of stroke, with specific conditions like gestational hypertension, preeclampsia, and chronic hypertension significantly raising the risk. For instance, preeclampsia is associated with an increased risk of both ischemic and hemorrhagic stroke. Other adverse pregnancy outcomes such as preterm birth, recurrent pregnancy loss, and gestational diabetes also increase stroke risk. Managing blood pressure and other pregnancy-related complications, along with monitoring for adverse pregnancy outcomes is important for stroke prevention during and after pregnancy.

Hormonal changes, particularly those associated with menopause, can increase stroke risk. A shorter reproductive lifespan is also identified as a potential risk factor for stroke. Hormone therapy (HT), especially estrogen-containing forms, increases the risk of stroke, particularly with oral formulations, in older women. Transdermal estrogen, especially at lower doses, is thought to carry less risk. The risk of stroke should be weighed against benefits when considering HT, especially for women over 60. In transgender individuals, gender-affirming HT is associated with a higher incidence of ischemic stroke in transfeminine people compared to cisgender women, although results for transmasculine people are inconclusive.

All forms of tobacco use, including cigarette smoking, water pipe smoking, and smokeless tobacco, significantly increase stroke risk. Cigarette smoking is linked to increased risk of ischemic stroke, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage. Environmental tobacco smoke exposure is also associated with higher stroke risk. While e-cigarette use is associated with an increased risk of stroke in some studies, it is complicated by the fact that many e-cigarette users also smoke cigarettes. Therefore, avoiding any form of tobacco use is essential for stroke prevention. Smoking cessation programs and counseling are recommended for current smokers and those using other tobacco products.

There is evidence linking periodontal disease (PD) with an increased risk of stroke. Individuals who receive dental prophylaxis or treatment for PD have shown significantly lower risks of stroke compared to those with PD who are not treated. A study comparing those who received full mouth teeth cleaning showed reduced stroke risk. This suggests that maintaining good oral hygiene through regular tooth scaling and other dental procedures can reduce stroke risk.

Palliative care is essential in stroke because it addresses the multidimensional impact of the condition on patients and their families. Stroke often results in physical disabilities, cognitive impairments, and psychosocial distress, significantly affecting quality of life. Palliative care is not just for end-of-life but aims to improve communication about goals of care and enhance the well-being of patients and their families across all stages of stroke. It emphasizes a holistic approach, addressing physical symptoms, emotional and spiritual needs, and the practical challenges of navigating the healthcare system and adjusting to a changed life. The focus is on maximizing quality of life for both patient and their family, regardless of the patient's prognosis.

While palliative care principles apply across many conditions, stroke has a unique trajectory of needs. Unlike diseases with a more predictable decline, stroke presents with varying degrees of recovery and disability and often creates profound and sudden changes in a person's identity and functioning. This unpredictability can lead to uncertainty for both patients and their families about what the future holds. Palliative care for stroke must adapt to these fluctuations and uncertainty, providing support at various stages of the disease, from acute care through long-term recovery, and also address the unique emotional, physical, and existential challenges that stroke survivors and their families experience. There is increasing recognition of the need for specialized “neuropalliative care” due to these nuances.

Palliative care needs in stroke are extensive and multidimensional. For patients, these include managing pain and other physical symptoms like spasticity and depression, providing emotional support to cope with loss of function and changes in identity, addressing psychosocial and spiritual distress, and ensuring that their care aligns with their values and goals. For family members, needs include emotional support, navigating complex treatment decisions, managing their own distress and burnout, and practical help with caregiving. This includes preparing for possible changes in prognosis and potentially providing guidance for end-of-life considerations. Palliative care should approach the patient and their family as a ‘unit of care’.

Significant racial and ethnic disparities are present throughout stroke care. Black and Hispanic individuals often experience higher stroke incidence, worse functional outcomes, and are less likely to receive timely acute stroke treatments. These inequities also extend to palliative care, with these groups being less likely to have advance directives, less frequently receive hospice care, and more often use long-term life-sustaining treatments. These disparities are not just about patient preferences but reflect systemic issues like structural racism and implicit bias within the healthcare system. There is a need for systematic interventions to address these inequities. This includes culturally tailored programs that can promote better understanding of and access to advance care planning, while also addressing the needs of the whole person.

The "total pain" concept highlights the multidimensional nature of suffering beyond just physical pain. In the context of stroke, this means considering physical, emotional, psychosocial, spiritual, and existential distress. It necessitates healthcare professionals explore the impact of the stroke on the patient's and family's lives, their expectations, values, and goals of care. This holistic approach is essential for providing person-centered and culturally sensitive care. It acknowledges that sources of distress can vary widely, and that individualized and proactive assessments are key to delivering appropriate support.

Time-limited trials are temporary periods of intensive medical care used to determine the effectiveness and appropriateness of a specific treatment, especially when the prognosis is unclear. This approach involves setting a time period during which a treatment is continued while closely monitoring the patient’s progress. At the end of this period, the care team and family discuss what was learned, reassess the goals of care, and decide on the next steps. Time-limited trials are particularly useful after a stroke, where uncertainty about the long term trajectory is common and helps families make tough decisions that align with patient’s preferences without making irrevocable choices too soon.

Post-acute palliative care for stroke is a largely understudied area. Most studies focus on end-of-life care, with little research on patients with stroke and their families navigating long-term recovery and disability. This is a major gap, considering stroke often leads to long-term disability. Palliative care needs should continue as patients transition to home, rehabilitation facilities, or long-term care facilities. Family members need resources, education and interventions such as caregiver support groups. Dyadic approaches, where both patient and caregiver receive support, show promise in reducing burden on caregivers and improving patient quality of life. Community-based models of palliative care delivery are being explored for stroke patients and their families who have complex needs.

End-of-life care for stroke patients emphasizes comprehensive symptom management, comfort measures, and emotional support for the patient and family. This includes regular assessments for pain and dyspnea (shortness of breath), which are often managed with medications like opioids and benzodiazepines. When the prognosis is estimated to be six months or less, and life-prolonging measures are not being pursued, hospice care is an appropriate consideration, and is designed to provide holistic support during the dying process. Hospice can take place in multiple settings, such as in the home, in assisted living facilities, or in hospice facilities. Hospice services also focus on supporting the family, including grief counseling, and may be covered by insurance programs such as Medicare. However, there is still a need for clear guidelines to facilitate earlier referrals for hospice care, especially for patients with stroke, due to the variability in the way end of life care is delivered for this population.

A large-core ischemic stroke refers to a stroke where a substantial portion of brain tissue has already been irreversibly damaged, also called infarcted. The definition of "large core" varies based on the time since the stroke onset. Within 6 hours of the stroke, it is typically defined as an Alberta Stroke Program Early CT Score (ASPECTS) of ≤5 based on non-contrast head CT or MRI. Beyond 6 hours and up to 24 hours, it is often defined as an ischemic core volume >50 mL to 70 mL as measured by CT perfusion or MRI. In clinical practice, CT perfusion volumes are combined with any additional hypodensity on non-contrast CT not visualized on CT perfusion to consider the full extent of the core. These definitions were used to select participants in recent trials on endovascular thrombectomy (EVT).

EVT is a minimally invasive procedure where a catheter is inserted into a blood vessel, usually in the groin, and guided to the blocked artery in the brain to physically remove the blood clot that is causing the stroke. Previously, it was thought that EVT would have little or no benefit in patients with large stroke cores, as the brain tissue was considered already infarcted and thus not salvageable. Therefore, most randomized clinical trials for EVT excluded patients with LCIS, usually using an ASPECTS score of less than 6 as the exclusion criteria.

Several recent randomized clinical trials, including RESCUE-Japan LIMIT, ANGEL-ASPECT, SELECT2, TESLA, TENSION, and LASTE have investigated the efficacy of EVT in patients with LCIS. These studies have shown that EVT can lead to improved outcomes, including functional independence and mobility, even in patients with large cores. This new evidence challenges the notion that large infarcts cannot benefit from reperfusion therapies.

The six trials showed that patients with LCIS who received EVT had significantly better functional outcomes compared to those who received medical management alone. Specifically, patients who underwent EVT were more likely to achieve functional independence, regain independent ambulation, and had a statistically significant shift in modified Rankin Scale scores. While the rate of achieving functional independence is modest (~19.5%) among all the trials, this rate was more than double that of medical management (~7.5%). Additionally, mortality rates were numerically more favorable in most trials, and in some cases significantly more favorable, for patients receiving EVT.

Eligibility criteria varied slightly across trials, but generally included adult patients with major arterial occlusions in the anterior circulation (internal carotid artery or middle cerebral artery) and a large ischemic core. Most trials required a minimum NIHSS score of 6. Imaging criteria varied as well: some studies (RESCUE-Japan LIMIT and LASTE) used MRI for ASPECTS assessment, while others (ANGEL-ASPECT and SELECT2) used a combination of non-contrast CT and CT perfusion. Additionally, some trials had age limits while others did not. The permitted time window from last known well also varied, from 6 hours in some trials up to 24 hours in others depending on the imaging criteria and techniques.

The primary risk associated with EVT is symptomatic hemorrhage, but the rates were relatively low and were not significantly higher in the EVT groups compared to the medical management groups across most trials. While the symptomatic hemorrhage rates in some individual studies are numerically higher in the EVT group, it was not a statistically significant difference. Rates of decompressive craniectomy, another potential risk in this population, also were not significantly different between groups. Overall, EVT did not demonstrate a substantial increase in the risk of complications compared to medical management.

Several limitations exist. The majority of participants in these trials did not have advanced age, vessel tortuosity, or significant pre-existing disability. The studies also included a very small proportion of patients with very large cores greater than 150mL. The majority of patients (close to 70%) were treated within 12 hours of symptom onset, with only small subsets treated later. There was also moderate heterogeneity in the study designs, imaging techniques, and patient inclusion criteria, which may have affected some results. Additionally, the treatment effect of EVT in patients with no core-penumbra mismatch on CTP is unknown as only about 7-9% of the study cohorts were found to have this. These limitations should be kept in mind when considering generalizability to all stroke populations.

Future research should focus on several key areas. Further studies are needed to determine the precise mechanism by which EVT benefits patients with LCIS, possibly by preventing further infarct expansion or improving tissue outcomes within ischemic beds. Patient-level pooled data analysis from trials could provide further insight into specific patient subgroups, the role of advanced imaging, and considerations for prognosis. Also, further data regarding cost-effectiveness, quality of life following treatment, and the prognostic value of hypodensity in the large core region are needed. Additionally, better data are needed on IVT use in conjunction with EVT as large core features are typically not an exclusion criterion for IVT if a patient presents within 4.5 hours of LKW, and the trials raise the possibility that IVT was offered less frequently within this window.

ARIA refers to brain edema (ARIA-E) or micro/macro hemorrhages (ARIA-H) that can occur with antiamyloid immunotherapies. These abnormalities are thought to result from the interaction of antibodies with amyloid-beta (Aβ) deposits in the brain's blood vessel walls (cerebral amyloid angiopathy, or CAA). While often asymptomatic, ARIA can sometimes lead to serious clinical symptoms, including headache, confusion, seizures, and focal neurological deficits. In rare instances, these can be severe or fatal, underscoring the importance of careful patient selection and monitoring.

Individuals with significant markers of CAA are at higher risk for ARIA. Clinical trials for drugs like aducanumab, lecanemab, and donanemab have excluded patients with more than 4 cerebral microbleeds, past intracerebral hemorrhage (ICH), or cortical superficial siderosis. Ischemic stroke, severe white matter hyperintensities (Fazekas grade 3) and more than 2 lacunar infarcts or a stroke involving a major vascular territory were also exclusion criteria. These exclusions were based on concerns that these patients were more likely to develop symptomatic ARIA. Individuals with these conditions should be evaluated carefully, with "caution" advised in current FDA labels and exclusion recommended in published Appropriate Use Recommendations.

APOE genotypes, particularly those containing the APOE ε4 allele, are associated with an increased risk of developing ARIA. This is likely because the APOE ε4 allele is linked to more severe CAA. While the exact mechanisms are still being studied, the presence of this genotype should be a considered in risk assessment of ARIA development.

The use of anticoagulants alongside antiamyloid immunotherapy increases the risk of symptomatic intracranial hemorrhage (ICH), potentially offsetting the benefits of treatment. Antiplatelet monotherapy seems to be better tolerated in this context. Dual antiplatelet therapy increases the risk of intracranial hemorrhage compared to monotherapy in patients with cardiovascular or cerebrovascular disease. Due to these risks, the FDA labels advise caution with antithrombotic agents and the Appropriate Use Recommendations discourage using anticoagulants until further safety data are available.

Thrombolytic administration carries a high risk of fatal ICH in patients undergoing Aβ immunotherapy. Since ARIA symptoms can mimic stroke, it's critical to determine if the symptoms are from a stroke or ARIA before starting thrombolytic therapy, as administering thrombolytics during ARIA could worsen the condition. Given this risk, a high level of caution or avoidance of thrombolytic use in patients receiving immunotherapy is a reasonable approach until more data regarding safety is available. In cases of large vessel occlusion, mechanical thrombectomy without thrombolytics may be considered a safer approach.

ARIA is detected (either through symptoms or MRI findings), the immunotherapy should be suspended. Treatment for symptomatic ARIA-E includes consideration of anti-inflammatory agents, such as corticosteroids, similar to what is done for CAA-related inflammation. For symptomatic ARIA-H presenting as ICH, treatment should follow existing guidelines for ICH management. The decision to resume immunotherapy should be made based on the resolution of both imaging findings and clinical symptoms and clinical judgement.

Emerging data suggests that controlling blood pressure is associated with a reduced risk of ARIA-E during donanemab treatment. Lower mean arterial pressure and the use of antihypertensive medications appear to independently reduce the incidence of ARIA-E. Strict adherence to guidelines for the management of hypertension might mitigate the risk of ARIA.

Ongoing research is focused on identifying more reliable predictors of severe ARIA, developing prevention and treatment strategies, and establishing clear guidelines for determining when benefits outweigh the risks for individual patients. Real-world data collection through registries like ALZ-NET will play a crucial role in advancing our understanding of the benefits and risks of these treatments.

Rural populations face numerous challenges that contribute to worse stroke outcomes. These include greater distances to hospitals and stroke centers, leading to delays in treatment; lower rates of arrival via Emergency Medical Services (EMS); fewer resources and staffing at rural emergency departments (EDs); and a higher prevalence of uncontrolled risk factors like hypertension, often compounded by issues of poverty and racial disparities. Rural patients also often have less access to specialized care such as mechanical thrombectomy and comprehensive rehabilitation services. Furthermore, rural hospitals are less likely to be certified as stroke centers, and when they are, these are more often based on self-initiation rather than need.

Significant challenges in prehospital care include longer travel times to stroke-capable hospitals, lower rates of EMS utilization, and decentralized EMS systems with inconsistencies in stroke assessment protocols and data collection. Volunteer EMS personnel, often with less training, are also more prevalent in rural areas. There's also a lack of awareness of stroke symptoms among rural populations, and public health campaigns are not always tailored to their specific needs.

Rural EDs often struggle with staffing shortages, including a lack of board-certified emergency medicine physicians, dependence on on-call technologists for CT scans, and a reliance on traveling nurses. The lower volume of stroke patients in rural EDs can lead to less experience in stroke care and diminished readiness, compounded by less established stroke protocols. Lack of participation in quality improvement initiatives further contributes to variations in the quality of care.

ASRH and PSC certification indicates that a hospital meets specific standards for stroke care. It's associated with better patient outcomes. Rural hospitals face financial and logistical barriers to certification, like low stroke volumes, challenges in hiring neurologists, and a lack of financial resources. Many rural hospitals are more likely to self-initiate certification rather than being selected based on community needs. They also find it more difficult to sustain these certifications compared to their urban counterparts.

Telehealth and telestroke can provide remote access to neurological expertise for rural hospitals, increasing the use of thrombolytic therapy and improving patient outcomes. However, barriers to widespread implementation include lack of reliable broadband internet access, funding issues, difficulty accessing infrastructure, resistance to adoption among clinicians, and the complexity of cross-state licensure regulations.

Given that rural areas often lack certified stroke centers with mechanical thrombectomy (MT) capabilities, interhospital transfer to more specialized facilities is necessary. Challenges in transfers include varying transfer protocols, limited availability of ambulances, long transport distances, and the potential for delays in care while transferring patients. Also, transfer decisions are not always based on need or patient outcomes, and bed availability and diversion statuses at receiving hospitals also influence transfers. Lack of standardized support protocols during transport further exacerbates risks.

Access to MT is limited by the geographic scarcity of accredited thrombectomy-capable centers and difficulty in transporting patients to them in time. The challenge extends from difficulties identifying patients that are likely to benefit from MT, delays in initial stroke identification, lack of EMS training in LVO identification, and lack of real-time awareness of available MT centers with interventionalists on call. Delays in the transfer process, especially door-in-door-out times, further hinders timely access to MT for rural populations.

A multi-faceted approach is necessary, including expanding ASRH and PSC certification, focusing on the equitable distribution of thrombectomy centers, expanding and incentivizing telestroke infrastructure, creating statewide policy standards for EMS assessment and routing, and standardizing and improving transfer protocols. Data integration and standardized registries are needed for continuous quality improvement. Policy changes should address workforce shortages, telemedicine reimbursement, and social determinants of health in rural communities. There should also be greater investment in under-resourced communities and multi-stakeholder collaboration.

The heart and brain are reciprocally linked. The heart delivers oxygen and nutrients vital for brain function, while the brain, through the autonomic nervous system, regulates heart activity. This interdependence is crucial, and disruptions in one system can adversely affect the other. This two-way connection highlights that the health of the heart is directly related to brain health and vice-versa. Adverse changes in brain structures (gray matter volumes, cortical thickness, white matter microstructure) have been associated with cardiac conditions, indicating a strong physiological link.

Three prevalent cardiac conditions are strongly linked to cognitive decline: heart failure (HF), atrial fibrillation (AF), and coronary heart disease (CHD). These conditions are associated with an increased risk of cognitive impairment and dementia through various shared risk factors, including inflammation, reduced blood flow, and microvascular damage. Understanding these links is vital for developing preventative and management strategies to protect both heart and brain health.

Heart failure, a condition where the heart doesn't pump blood effectively, can lead to structural and functional brain damage through several pathways. Reduced blood flow, inflammation, and neurohormonal activation are key contributors. Specifically, reduced cerebral blood flow leads to oxidative stress, inflammation, and neuronal dysfunction, all of which are associated with cognitive impairment. Additionally, structural changes in the heart, even in midlife, can be associated with cognitive decline later in life, even independently of other vascular risk factors or history of stroke, atrial fibrillation, or coronary heart disease. There is also some research suggesting genetic links may be present between heart failure and neurodegeneration.

Atrial fibrillation, an irregular heartbeat, is associated with an increased risk of cognitive impairment and dementia, even in the absence of stroke. Although some of the cognitive decline can be attributed to shared risk factors (e.g., hypertension, diabetes, heart failure), AF is also associated with brain changes such as white matter hyperintensities and silent brain infarcts. Cerebral microhemorrhages, common in AF patients, are associated with cognitive decline. Reduced cardiac output resulting from AF can also compromise blood flow to brain areas involved in cognition. Moreover, inflammation associated with AF can affect brain structure and contribute to cognitive impairment. These effects suggest that managing AF effectively is important for brain health.

Coronary heart disease, characterized by narrowed blood vessels supplying the heart, elevates the risk of cognitive decline and dementia. The impact is often linked to shared risk factors like vascular disease and inflammation. CHD also contributes to inflammation, which can compromise the cerebrovascular system, affecting blood-brain barrier permeability and potentially leading to neuroinflammation. Microvascular dysfunction affecting both the heart and brain is also associated with reduced blood flow and cognitive decline. Additionally, cardiac sequelae such as arrhythmia and low cardiac output from CHD can lead to cerebral hypoperfusion, further impacting brain health and cognition.

Several strategies are proposed, such as improving blood flow and addressing stroke volume in heart failure. Also, anticoagulation or rhythm control in atrial fibrillation can decrease dementia risk. Additionally, managing vascular risk factors (VRFs) like hypertension, diabetes, and high cholesterol can preserve cognitive function in those with CHD. Furthermore, some studies suggest that implementing multidomain interventions that include diet, exercise, cognitive training, and VRF control can enhance neurocognitive performance. These findings suggest a holistic approach is most effective. In regards to treatments specifically, it is important to know that the long-term cognitive effects of common treatments used for heart conditions have not yet been definitively demonstrated and requires additional research.

Systemic inflammation, often associated with heart conditions, can contribute to neuroinflammation, affecting the brain through a disruption in the blood-brain barrier. Increased permeability of the BBB can allow harmful substances to enter the brain tissue and cause neuroinflammation, particularly in the white matter. This inflammatory response in the brain may then promote cognitive decline and is associated with activation of microglia cells. Both heart conditions and neurodegenerative diseases, such as Alzheimer's, share inflammatory profiles, suggesting a complex interplay between systemic and neuro-inflammation in heart and brain health.

Current research is still limited by the lack of evidence that appropriate management of cardiac conditions has a beneficial effect on cognitive decline. Additionally, standardized cognitive and functional outcomes are not always integrated into cardiovascular trials which can lead to inconsistencies. Further investigation into the impact of therapies on brain health is needed. Other factors like social determinants of health, genetic factors, and the role of the glymphatic system also require exploration. Furthermore, there is a need to include diverse populations in research to ensure findings can be generalized and improve our understanding of the heart-brain link across demographics.

Systemic complications following a stroke are non-neurological issues that affect various organs and bodily systems. These complications can arise from the direct tissue damage caused by the stroke, its impact on physiological functions, or as adverse effects of diagnostics or treatments. They are crucial to address because they significantly affect patient care, resource allocation, and overall outcomes, including increased mortality, longer hospital stays, and long-term disability. These complications can arise from the stroke itself or from other factors related to diagnostics or treatments. They are a major cause of early mortality after a stroke.

The frequency of post-stroke systemic complications varies widely, ranging from 13.9% to 95% in studies. This variability stems from differences in study methodologies, patient selection, methods of assessment, and statistical analysis. A significant portion of these complications arises shortly after a stroke, making early management critical. Factors such as stroke severity, the presence of hemorrhagic stroke, and the extent of tissue damage contribute to a higher risk of these complications. Additionally, stroke can weaken the immune system making patients susceptible to infections.

Fever is frequently observed after a stroke, with elevated body temperature occurring in 60% to 90% of stroke patients within 72 hours of onset. It can arise from both infectious and non-infectious causes. Non-infectious causes include autoimmune disorders, drug reactions, venous thromboembolism, or a central fever due to cerebrospinal fluid inflammation. The challenge lies in differentiating fever from hyperthermia and identifying the underlying cause, as conventional fever treatments may not always be effective. While fever is associated with poor outcomes, the optimal approach for fever management to improve outcomes is still under investigation.

Stroke-associated pneumonia (SAP) is a common and severe infection occurring after a stroke. It is a leading cause of early mortality in stroke patients. It differs from other pneumonias due to its unique clinical setting, pathophysiology, and microbiology. Stroke patients can develop reservoirs of pathogens in their upper respiratory system. Stroke-related issues like dysphagia, impaired cough, and reduced consciousness facilitate the migration of these pathogens into the lungs. Also, stroke-induced immunosuppression makes patients more susceptible to infections, often caused by aerobic gram-negative bacilli and gram-positive cocci. SAP is difficult to diagnose because it can be confused with other causes of fever and respiratory issues common post-stroke.

Oral health care is a crucial yet often neglected aspect of post-stroke care. Stroke patients are more prone to poor oral health which increases the risk of SAP through the aspiration of oral biofilm. Hospital settings often face challenges in providing adequate oral care due to stroke-related deficits that hinder self-care. Currently, there is insufficient evidence on how to best provide oral health care in the acute phase after stroke, but the current recommendations include a standardized oral assessment on admission, twice-daily brushing and suctioning for high-risk patients, and establishing pathways for staff education and dental referrals.

Besides pneumonia, stroke patients can experience other respiratory issues such as venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism (PE). Breathing disorders like sleep-disordered breathing (SDB), often manifesting as obstructive sleep apnea (OSA), are common and can affect patient outcomes. Management includes oxygen supplementation for hypoxemia, risk assessment for PE, and individualized anticoagulation therapy. While some studies show potential for positive airway pressure for OSA in stroke patients, the evidence is not yet conclusive, and routine screening is not recommended.

Dysphagia, or swallowing impairment, is common post-stroke, increasing the risk of pneumonia and malnutrition. Management focuses on early detection through dysphagia screening (DS) conducted by nurses or clinicians before initiating oral intake of food or medication. Formal assessments by speech-language pathologists follow failed screenings. Treatment includes dietary modifications and alternative feeding methods, such as nasogastric tubes or percutaneous gastrostomy (PEG) tubes. While PEG placement is common, its impact on overall outcomes remains debated, and shared decision-making with patients and families is essential in this regard.

Transitions of care are challenging because of the complexity of managing post-stroke complications, requiring close coordination among healthcare providers, patients, and caregivers. Issues such as post-stroke disabilities, cognitive and communication problems, transport limitations, varied discharge destinations and varying availability of resources all create obstacles. Improvement requires interdisciplinary teams, including physicians, nurses, and rehabilitation specialists, along with effective communication, caregiver support, and consideration of social and economic factors. Addressing the challenges during transitions of care is critical for stroke survivors, as this is when many complications arise and impact recovery.

CVT is the presence of a blood clot in the dural venous sinuses, the cerebral veins, or both. It is a relatively rare type of stroke, accounting for only 0.5% to 3% of all stroke cases. However, it disproportionately affects certain populations, particularly those under 55 years old, with a higher incidence in women. The most commonly affected sinuses are the superior sagittal, transverse, and sigmoid sinuses, as well as deep cerebral veins.

The clinical presentation of CVT is highly variable. Headache is the most common symptom, occurring in approximately 90% of cases, with other symptoms often stemming from increased intracranial pressure or focal parenchymal injury. These include nausea, vision problems (transient visual obscurations, vision loss, double vision), papilledema, and cranial neuropathies. Seizures occur in 20% to 40% of patients, and focal neurological deficits are seen in 20% to 50% of cases. Symptoms often develop more slowly than other types of stroke, usually over more than 48 hours. However, a small percentage may present more acutely with a thunderclap headache or sudden neurological deficits.

CVT risk factors can be transient or chronic. Major risk factors include: oral contraceptive use and pregnancy/postpartum period (especially in women); acquired thrombophilias, such as antiphospholipid antibody syndrome and JAK2 mutations; genetic thrombophilias; cancers, particularly myeloproliferative disorders; autoimmune diseases; infections (including COVID-19 and head/neck infections); dehydration; certain medications (e.g., corticosteroids, l-asparaginase); and mechanical factors like head trauma, neurosurgical procedures, and compressive lesions of the venous sinuses. Obesity is also a risk factor. Additionally, vaccine-induced thrombotic thrombocytopenia (VITT) has emerged as a rare but important risk factor.

Diagnosis of CVT involves both clinical suspicion and imaging confirmation. Initial brain scans often include non-contrast CT or MRI to identify direct (thrombus) and indirect signs (venous infarction, hemorrhage, edema) of venous occlusion. CT venography (CTV) and magnetic resonance venography (MRV) are optimal tests for confirming CVT. CTV clearly depicts the venous system, while MRV (particularly contrast-enhanced MRV) is useful for visualizing thrombus in smaller veins. Gradient-recalled echo or susceptibility-weighted imaging sequences help identify inconspicuous findings, especially cortical vein thrombosis. Advanced MRI techniques like black-blood imaging are also promising.

The primary treatment for CVT involves anticoagulation to prevent thrombus growth and recurrence. Low-molecular-weight heparin (LMWH) is often the initial choice over unfractionated heparin, followed by transition to oral anticoagulants. Traditionally, vitamin K antagonists (VKAs), like warfarin, have been used for 3 to 12 months for transient risk factors or indefinitely for chronic major risk factors. However, direct oral anticoagulants (DOACs), such as dabigatran, rivaroxaban, and apixaban, have emerged as a safe and effective alternative to VKAs, with evidence showing similar efficacy and fewer major hemorrhages. Endovascular therapies (EVT) are generally reserved as rescue treatments for those with clinical deterioration despite medical therapy or contraindications to anticoagulation due to their higher risks and lack of established benefit over medical management alone.

Although most patients with CVT achieve functional independence, many experience long-term residual symptoms including cognitive impairment, fatigue, mood disturbances, and persistent headaches that can negatively affect their quality of life and ability to return to work or school. The risk of recurrent venous thromboembolism (VTE), including CVT, ranges from 1% to 4% per year. Higher risks are seen in those with severe thrombophilia, a history of VTE, and those with unidentifiable underlying causes. Aspirin has shown some efficacy in secondary prevention of VTE but should be considered in shared decision-making with the individual patient.

In children, CVT is more common in neonates and can be associated with infections, dehydration, iron deficiency, anemia, and head trauma. Treatment involves heparin followed by LMWH, VKAs, or rivaroxaban. Anticoagulation for at least 6 weeks is advised, and both duration of anticoagulation and use of DOACs are areas of current research. Pregnancy and the postpartum period are major risk factors for CVT due to hormonal and coagulation changes. VKAs are contraindicated during pregnancy due to risks of embryopathy and bleeding. LMWH is the preferred anticoagulant during pregnancy and the postpartum period and should be considered for subsequent pregnancies. It is generally considered that CVT during pregnancy does not contraindicate future pregnancies, with LMWH prophylaxis often recommended in those subsequent pregnancies.

VITT is a rare but serious condition characterized by thrombocytopenia and thrombosis, including CVT, occurring after vaccination with adenovirus-based SARS-CoV-2 vaccines. Symptoms develop within 5-24 days of vaccination, often presenting with headache and thrombocytopenia. VITT is believed to be caused by the formation of platelet factor 4 antibodies. The management of VITT involves avoiding heparin products, and the use of intravenous immunoglobulin, steroids, and non-heparin parenteral anticoagulants, transitioning to oral anticoagulants (DOACs) once platelet counts recover. mRNA vaccines do not appear to be associated with VITT.

Cervical Artery Dissection (CAD) involves a tear in the inner layer of an artery in the neck, specifically the internal carotid or vertebral arteries. This can lead to the formation of a blood clot, vessel narrowing (stenosis), blockage (occlusion), or a dissecting aneurysm. CAD is concerning because it can cause local symptoms, like pain, cranial nerve compression or more seriously, strokes due to reduced blood flow to the brain or spinal cord. It is particularly significant as a cause of stroke in younger adults, accounting for up to 25% of strokes in individuals under 50 years old.

Common symptoms of CAD include headache (often described as facial, frontal, temporal, or occipital/cervical), neck pain, and less commonly, partial Horner syndrome (drooping eyelid, constricted pupil, decreased sweating), cranial nerve palsies, and pulsatile tinnitus (ringing in the ears). These symptoms often precede any signs of stroke. Diagnosis is typically done through imaging, with Magnetic Resonance Imaging/Angiography (MRI/MRA) or Computed Tomography Angiography (CTA) being preferred. While historically Digital Subtraction Angiography (DSA) was the standard, it is avoided as a first-line tool due to risks, and is typically only considered if MRI and CTA are inconclusive. Ultrasound can be useful for follow-up imaging.

CAD is caused by a combination of factors including comorbidities, minor trauma, anatomical and congenital abnormalities, and genetic predispositions. Specific factors may include:

• Minor Trauma: Neck manipulation, extreme head movements, heavy lifting, and some sports activities.
• Anatomical Factors: An elongated styloid process (Eagle syndrome) or increased vascular tortuosity.
• Genetic Factors: Connective tissue disorders (e.g., Marfan syndrome, Ehlers-Danlos syndrome), and specific genetic variants such as PHACTR1 gene mutations.
• Other Factors: Recent systemic infections (more common in carotid artery dissection), fibromuscular dysplasia, and potentially migraine. Risk factors can also vary depending on the location of the dissection with minor trauma being more associated with vertebral artery dissection and recent infection more associated with carotid artery dissections.

The primary antithrombotic options for CAD are antiplatelet therapy (like aspirin or clopidogrel) and anticoagulation therapy (like vitamin K antagonists (VKA) or direct oral anticoagulants). The choice of treatment is individualized based on the patient's risk of ischemic stroke and bleeding.

• Anticoagulation: May be preferred in patients with low risk of intracranial hemorrhage but a high risk of ischemic stroke, for example those with intraluminal thrombus or an occlusive dissection.
• Antiplatelet therapy: A short course of dual antiplatelet therapy may be preferred when safe, particularly in patients that would otherwise qualify for dual antiplatelet therapy in minor stroke/TIA. Antiplatelet monotherapy may be used in patients at risk of intracranial hemorrhage.

Antithrombotic therapy is typically continued for 3 to 6 months. If remodeling is not occurring, some people may remain on antithrombotic treatment for longer, and should take into account individual risk factors and imaging results.

The risk of recurrent CAD is low, about 1-2% per year. However, the risk is highest in the first few months after the initial diagnosis. Factors that increase the risk of recurrence include younger age and the presence of fibromuscular dysplasia or a history of migraine. Lifestyle modifications are important, particularly in the months immediately following a CAD diagnosis. It is important to avoid activities that increase the risk of cervical injury, such as neck manipulation, and heavy lifting for 1-6 months after diagnosis to allow for vessel healing. In high risk individuals (those with a known connective tissue disorder or recurrent dissection), avoiding such activities should be lifelong.

Genetic testing is not routinely recommended for all patients with CAD. It is reasonable to screen for signs of monogenic connective tissue disorders (e.g., recurrent dissections, family history) and appropriate genetic testing and counseling should be conducted based on results of screening. Routine genetic testing in the absence of these signs is generally not suggested due to its increased cost and low yield. However, genetic testing can be considered in patients with recurrent dissections.

After a diagnosis of CAD, it is reasonable to screen for cerebral aneurysms and aortic root dilation. In individuals with hypertension or evidence of fibromuscular dysplasia, screening for renal artery stenosis with a renovascular Doppler is also reasonable. Aortic root dilation has been found to be more prevalent in patients with CAD, and there is a correlation between CAD and fibromuscular dysplasia.