The multiple sources, pathophysiologic mechanisms, and sequelae of stroke are reflected in the diverse types of cerebrovascular disorders. The World Health Organization classifies cerebrovascular diseases under "Diseases of the nervous system" in the 11th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-11), the international standard diagnostic classification for all general epidemiologic purposes and many health management purposes (Table 2) [22]. TIAs and traumatic intracranial hemorrhage are also included in the nervous system disease category in the ICD-11; vascular dementia is not. Its exclusion illustrates the heterogeneity of stroke and its sequelae. Vascular dementia, listed as dementia due to cerebrovascular disease, is categorized under "Mental, behavioral, or neurodevelopmental disorders: Neurocognitive disorders."

Subarachnoid hemorrhages occur less frequently than ICHs. The hallmark of subarachnoid hemorrhage is the immediate onset of a severe headache with signs of meningeal irritation [36]. Individuals may describe this headache as their "worst ever." Nausea, vomiting, neck pain, and photophobia are also classic symptoms, although they are not always present [36]. Neurologic deficits may be acute or may manifest hours to days after the onset of bleeding.

As with any stroke, the symptoms of TIA depend on the affected vascular territory. For instance, involvement of the carotid artery causes disturbances in the ipsilateral eye or brain [49]. Although the most common focal neurologic signs of TIA are sudden-onset unilateral weakness and numbness or tingling in a limb, a TIA can cause any of the following symptoms [49,50]:

As noted, the risk of ischemic stroke is high in the period following a TIA. A meta-analysis found that approximately 5% of patients who have a TIA will have an ischemic stroke within the next 7 days [11,43]. The risk of stroke within three months after a TIA is approximately 10%; the cumulative risk approaches 25% over the ensuing 5 years [11]. Prompt initiation of secondary prevention strategies for TIA and minor stroke with existing therapies has been shown to reduce the risk of early recurrent stroke by 80% [48]. AHA/ASA guidelines support the concept that, with few exceptions, secondary prevention in patients who present with TIA is the same as that for those with ischemic stroke [10]. A 2020 clinical practice review and 2023 AHA published statement on diagnosis and management of TIA provide updated clinical guidance [399,402]. Selected key principles are as follows:

As noted, the risk of ischemic stroke is high in the period following a TIA. A meta-analysis found that approximately 5% of patients who have a TIA will have an ischemic stroke within the next 7 days [11,43]. The risk of stroke within three months after a TIA is approximately 10%; the cumulative risk approaches 25% over the ensuing 5 years [11]. Prompt initiation of secondary prevention strategies for TIA and minor stroke with existing therapies has been shown to reduce the risk of early recurrent stroke by 80% [48]. AHA/ASA guidelines support the concept that, with few exceptions, secondary prevention in patients who present with TIA is the same as that for those with ischemic stroke [10]. A 2020 clinical practice review and 2023 AHA published statement on diagnosis and management of TIA provide updated clinical guidance [399,402]. Selected key principles are as follows:

Within minutes of the onset of ischemic stroke, the core of an infarct can begin to form at the least-perfused site. This site is encircled by an area partially altered metabolically and ionically by cytotoxic edema [55]. This area, the ischemic penumbra, is structurally intact and generally salvageable if reperfusion is achieved promptly. Because cerebral function deficits develop rapidly (within minutes to hours) as an ischemic stroke progresses, these brain attacks are a medical emergency. Each minute that passes results in an average loss of 1.9 million neurons and 14 billion synapses; an ischemic brain ages 3.6 years for every hour that passes after the onset of stroke [56]. For this reason, stroke specialists use the mantra, "time is brain." Although irreversible damage occurs, most individuals with stroke have recoverable penumbral tissue for at least three hours following the onset of symptoms [16].

Posterior circulation is primarily composed of the vertebrobasilar artery, the posterior cerebral artery, which it supplies, and other branching vessels. The posterior cerebral artery provides blood to the occipital and medial temporal lobes, as well as regions of the midbrain, subthalamic nucleus, basal nucleus, thalamus, mesial inferior temporal lobe, and occipitoparietal cortices. The two main segments of the posterior cerebral artery (P1 and P2) are connected by the posterior communicating artery. The Circle of Willis links the anterior and posterior circulation at the base of the brain.

AF is the most common cardiogenic cause of embolic stroke, and the proportion of strokes caused by AF increases with increasing patient age. The presence of AF increases the risk of embolic stroke fivefold and doubles the risk of death [76,77]. Atrial fibrillation is associated with blood stasis and thrombus formation within the left atrial appendage. Other cardiogenic sources of brain embolism include valvular thrombi (e.g., rheumatic disease, endocarditis, prosthetic valves), mural thrombi from myocardial infarction (MI) or severe heart failure, and paradoxical embolization across a patent foramen ovale [78,79]. MI is associated with a 2% to 3% incidence of embolic stroke, 70% of which occur in the first week after the event [77,79].

Approximately 16% of men and 14% of women have a stroke by 85 years of age, and stroke is the fifth leading cause of death in the United States, accounting for more than 150,000 deaths in 2019 [1,3,84]. Morbidity associated with stroke is also high, with at least 65% of stroke survivors having some sort of impairment [85]. At three months after a stroke, approximately 20% of survivors depend on long-term care. Between 15% and 30% of stroke survivors are permanently disabled [86]. A six-month follow-up of ischemic stroke survivors (65 years of age and older) demonstrated that [87]:

Prolonged damage of the aging cardiovascular system by various risk factors for stroke doubles the risk of ischemic stroke for each decade of life after 55 years of age [9]. Thus, clinicians should be sensitive to their patients' modifiable risk factors, most notably hypertension, starting at an early age [1]. As many as 70% of strokes occur in individuals older than 65 years of age, and the average age at the time of ischemic stroke is 71 years in men and 75 years in women [1]. Stroke patients 85 years of age and older comprise 17% of all stroke patients [1]. Clinicians should be particularly aware of silent cerebral infarctions in older individuals, as these infarctions occur more commonly in this population [89].

The 2017 Guideline for High Blood Pressure in Adults recommends screening every 2 years for adults with a blood pressure less than 120/80 mm Hg and screening every 3 to 6 months for people with systolic blood pressure of 120 to 129 mm Hg or with diastolic blood pressure greater than 80 mm Hg [125]. The AHA/ASA recommends that women be screened for high blood pressure before taking birth control pills, as the combination increases the risk of stroke [126].

Although public knowledge regarding the warning signs and risks of stroke has improved, the majority of the general public is still unaware that early treatment can prevent severe disability and death [133,134]. Estimates vary widely, however; the International Stroke Trial found that only 4% of patients with acute ischemic stroke arrive at the emergency department (ED) within 3 hours after the onset of symptoms, and a separate study found that 21% to 25% of individuals with acute ischemic stroke arrive at an ED within the same timeframe [135,136]. Of these individuals, 2% to 4% receive thrombolytic treatment [137,138]. It has been estimated that if all individuals called for emergency help at the onset of symptoms, as many as 29% could realistically receive treatment within 3 hours [137]. In addition, if all patients arrived at the ED within 1 hour after known symptom onset and received optimal treatment, the projected rate of thrombolysis would be 57%.

The numerous nonmodifiable and modifiable factors that contribute to the risk of stroke have been discussed. Although many of these are independent risk factors, their interactions can affect predictions and management decisions in unexpected ways. No simple, validated stroke risk-assessment tool is currently available [9]. Although risk-assessment tools may have some utility, it is unknown if they improve primary prevention, especially when applied across subgroups according to age, gender, and race/ethnicity [9,144].

Because TIA is a substantial risk factor for a subsequent stroke, clinicians in many EDs are stratifying such patients by degree of risk with use of the ABCD or ABCD2 assessments [145,146]. The ABCD clinical tool is designed to predict 7-day risk of stroke through assessment of age (1 point for patients 60 years of age or older), blood pressure (1 point for a blood pressure greater than 140/90 mm Hg), clinical features (2 points for unilateral weakness with or without speech impairment or 1 point for speech impairment without weakness), and duration (1 point for 10 to 59 minutes, 2 points for greater than 59 minutes) [147]. The "2" designation in ABCD2 was added to represent the presence or absence of diabetes. The effectiveness of these screening tools is lessened by the fact that some individuals do not seek emergency care for a TIA or do not report a TIA to their clinician. However, the ABCD2 assessment has been shown to identify 21% of individuals with a high 2-day risk of having an ischemic stroke [145]. Individuals with high-risk TIA require the same intensity of evaluation and stroke prevention as individuals with ischemic stroke. Scores that predict future stroke risk should be used in conjunction with other diagnostic studies (e.g., imaging) and laboratory tests. The use of ED diagnostic protocols and observation units can reduce length of stay while improving patient treatment and reducing stroke rate [148,149].

If a patient presents with classic signs of stroke and has one or more cardiovascular risk factors, the diagnosis of stroke can be straightforward. However, identifying more unusual cases may be a challenge. If fever and a cardiac murmur are present, the cause of the stroke may be infective endocarditis [156,157]. Giant cell arteritis may be the cause if the patient is 50 years of age or older, has a prominent history of headache, and a strikingly elevated erythrocyte sedimentation rate. The presence of ptosis and miosis contralateral to the deficit may suggest carotid artery dissection [156,157]. If the symptoms were maximal at their onset, a subarachnoid hemorrhage or embolic stroke should be suspected [158]. In up to 40% of patients with subarachnoid hemorrhage, a severe headache (sometimes called a thunderclap or sentinel headache) that may abate within minutes or hours is the only symptom [158]. Head CT should be immediately performed in any patient with a suspected subarachnoid hemorrhage [36].

Comprehensive stroke centers are designed to accommodate the needs of patients with complicated forms of stroke, intracranial hemorrhages, and subarachnoid hemorrhages, as well as patients in need of aggressive intervention measures and intensive care [19]. In general, primary and comprehensive stroke centers have been shown to be associated with better adherence to evidence-based guidelines and with an increased use of IV rt-PA [181]. Nationally, only 2% to 3% of individuals with stroke are treated with rt-PA, but the rate is typically greater than 10% at primary and comprehensive stroke care centers [19,138]. Overall care may also be improved at comprehensive stroke centers [181,182]. A formal certification process for comprehensive stroke centers has been established by the Joint Commission and the ASA. The Joint Commission has been certifying primary stroke centers since 2004, and it began providing certification for comprehensive stroke centers in 2014 [16]. Because patients are more likely to receive thrombolytic therapy at primary and comprehensive stroke centers, many states have enacted policies mandating the direct routing of individuals with suspected stroke (with onset of symptoms less than 3 hours previously) to either of these types of facilities. As of 2015, 1,505 of the 4,640 general hospitals and emergency rooms in the United States have been certified as primary stroke centers [183]. Seventy-four percent of the primary stroke centers have been certified by the Joint Commission and the AHA/ASA, 20% have been certified by state organizations, and 6% have been certified by other organizations. The highest proportion of primary stroke center certifications has occurred in the Northeastern United States [183]. Telemedicine for stroke (also called telestroke) and air transport are being increasingly used to serve individuals in rural areas that lack local stroke expertise [16,182].

The most common serious medical complication of rt-PA is secondary brain hemorrhage, which occurs in 6% of patients [188]. Yet, the risk does not outweigh the benefits of rt-PA. Three months following rt-PA therapy, approximately 30% of patients are neurologically normal or near normal; 30% have mild-to-moderate neurologic deficits; 20% have moderate-to-severe deficits; and 20% have died [189]. Other dangerous complications of rt-PA, although rare, are angioedema, anaphylaxis, systemic hemorrhage, and, if rt-PA is administered soon after an acute MI, myocardial rupture [16,190].

Rehabilitation in an inpatient stroke unit has been associated with better outcomes than rehabilitation in a general healthcare facility, with improved quality of life, survival, and functional status at five years [17,21,245,246,247,248,249]. Yet the decision to refer a stroke patient to a particular setting after discharge involves a complex set of demographic, clinical, and nonclinical factors that are also inevitably related to patient outcomes [21]. Variations in inpatient stroke rehabilitation outcomes have been found among racial/ethnic populations [21,250,251,252,253,254]. Black individuals have less functional improvement at discharge compared with White individuals and are more likely to be discharged to home despite worse functional independence measure (FIM) scores [255]. Asian individuals have functional improvements similar to those for White individuals but have less improvement at 3 months after discharge [255]. These disparities point to the need for focused attention on appropriate rehabilitation services for minority populations.

Pressure ulcers are a commonly encountered complication in hospital and long-term care facilities, occurring in approximately 10% and 25% of patients in those settings, respectively [286]. According to the National Pressure Ulcer Advisory Panel, a pressure ulcer is a "localized injury to the skin and/or underlying tissue usually over a bony prominence, as a result of pressure, or pressure in combination with shear" [287,288]. Although ulcers typically occur proximal to osseous prominences (e.g., the sacrum, hips, ankles), skin breakdown at the ears is also common in certain settings [289,290]. Most pressure ulcers are associated with deep tissue injury [291]. Regular assessment of skin and the use of objective risk scales (e.g., the Braden scale) may help prevent skin injury and should be followed by regular skin inspection with documentation [21,292]. Risk factors for pressure ulcers include [286]:

The D-dimer test alone is not recommended to rule out DVT in patients who have had a stroke. Patients with intermediate-to-high risk for DVT should be screened with use of ultrasonography. This imaging modality may not detect DVT in the calf, however, and repeat ultrasonography or venography should be used when DVT in the calf is suspected. Contrast venography was previously the most definitive test for the diagnosis of DVT, but today, Doppler ultrasound is the diagnostic study of choice [299].

Large infarcts, aphasia, cognitive impairment, functional disability, lesions in the frontal cortex or frontoparietal lobes, and advanced age are associated with post-stroke urinary dysfunction [310]. Medications such as diuretics, alpha-adrenoreceptor blockers, and anticholinergic drugs can cause or exacerbate this complication [311,312]. Hyper-reflexia and hyporeflexia are the most common mechanisms of urinary incontinence in stroke survivors [313]. Detrusor sphincter dyssynergia, a cause of incomplete bladder voiding, is uncommon because its pathogenesis involves lesions between the brain stem and spine [312]. When assessing bladder function in patients with acute stroke, it is important to evaluate urinary retention with use of a bladder scanner or an in-and-out catheterization; urinary frequency, volume, and control; and the presence of dysuria. Patients who have urinary incontinence may benefit from bladder-training regimens and scheduled voiding [311,314].

Fecal incontinence can be due to neurogenic impairments or leakage around a fecal impaction (overflow incontinence) [315]. If the underlying cause of fecal incontinence is neurogenic, the signs and symptoms would likely include reduced rectal sensation and tone, inability to voluntarily contract the rectal sphincter, and stool in the rectal vault [315]. A diagnosis of constipation with overflow incontinence is more likely if the patient has rectal sensation and tone.

Risk factors for impaction and constipation include immobility, inactivity, dehydration, some medications, mood disorders, and cognitive deficits [316,317]. Multivariate analysis has shown that advanced age and diabetes are risk factors for fecal incontinence [317]. Patients with persistent constipation or fecal incontinence may benefit from bowel-management programs and psychosocial support [318]. Because of the risk of skin breakdown, the social stigma, and the burden of care associated with bowel and bladder incontinence, management is an essential component of the rehabilitation process [21].

Within 12 weeks after a stroke, approximately 25% of patients will fall [286]. Up to 70% of individuals with a stroke fall during the first six months after discharge from the hospital or rehabilitation facility [21,319]. Individuals with stroke are also at risk of repeated falls that include injury [21,320]. One study found that most falls occur at home in the first 3 months following post-stroke risk assessment [320]. Falls are a common complication for several reasons, including [315,321,322]:

The Berg Balance Scale may be the most appropriate screen for patients who are likely to fall [21,323,324]. This scale tests 14 specific functional movements of daily living of increasing difficulty [325]. The 56-point maximum score indicates adequate balance and low risk of a fall. A score of less than 45 is associated with a proclivity for falling [323,325]. The score at 2 months post-stroke is useful for informing a patient's risk of falls, but it does not account for the multifactorial nature of the problem and should not preclude risk management provided in conjunction with exercise interventions, such as rehabilitation that targets gait coordination, to improve mobility [320,326]. If the patient is able to walk, the Stops Walking When Talking test may further help to identify the risk for a fall [323]. With this test, the examiner initiates a conversation with the patient while walking; if the patient stops walking to respond, the risk of a fall is increased [327]. St. Thomas' Risk Assessment Tool in Falling Elderly Inpatients (known as STRATIFY), a tool used commonly in the rehabilitation setting, has been shown to be a poor predictor of the risk for fall when screening patients with stroke [328].

In addition to the physical consequences associated with falls, there are also psychologic and social consequences. Impairments in balance, gait, motor control, perception, and vision contribute to a heightened fear of falling in the stroke survivor, with 30% to 80% reporting various levels of fear associated with falling and mobility [21]. This fear can cascade into reduced levels of physical activity and deconditioning, resulting in greater physical decline, loss of ability to perform activities of daily living, loss of independence, social isolation, and depression. Education in fall prevention and balance training are essential components of the rehabilitation process [21].

Pain is one of the most frequently experienced complications. Almost one-half of all stroke survivors experience chronic pain, 65% of whom have shoulder pain [286]. Whether chronic or periodic, pain can delay functional recovery by masking motor function improvement, diminishing a patient's motivation or willingness to perform rehabilitative tasks, or limiting the patient's movement or requiring the use of a cane or wheelchair for ambulation [17]. Pain most often results from joint immobilization and the fixation of tendons and ligaments in one position [85]. In some patients, however, stroke-induced sensorimotor pathway damage leads to the sensation of pain in an affected extremity or side of the body. The most common pain syndrome of this type is central post-stroke pain, which affects 8% of patients, or at least 56,000 stroke patients in the United States each year [21,329,330]. Four percent of patients with central post-stroke pain experience it as shoulder pain. Central post-stroke pain can be difficult to manage, even with medications. Only amitriptyline and lamotrigine have been shown to be effective in placebo-controlled studies [331].

Pain is one of the most frequently experienced complications. Almost one-half of all stroke survivors experience chronic pain, 65% of whom have shoulder pain [286]. Whether chronic or periodic, pain can delay functional recovery by masking motor function improvement, diminishing a patient's motivation or willingness to perform rehabilitative tasks, or limiting the patient's movement or requiring the use of a cane or wheelchair for ambulation [17]. Pain most often results from joint immobilization and the fixation of tendons and ligaments in one position [85]. In some patients, however, stroke-induced sensorimotor pathway damage leads to the sensation of pain in an affected extremity or side of the body. The most common pain syndrome of this type is central post-stroke pain, which affects 8% of patients, or at least 56,000 stroke patients in the United States each year [21,329,330]. Four percent of patients with central post-stroke pain experience it as shoulder pain. Central post-stroke pain can be difficult to manage, even with medications. Only amitriptyline and lamotrigine have been shown to be effective in placebo-controlled studies [331].

Calculation, executive functioning (the integration of multiple and complex processes), and visual perception/construction are the cognitive arenas most often affected during the first several weeks after a stroke [335,336]. Up to 88% of patients with a cerebellar stroke have cognitive deficits, such as impairments in abstract thought, attention, control, memory, planning, and speech [337]. In many cases, patients with stroke-associated right brain damage have anosognosia, a condition in which patients are rendered unaware of their contralateral sensory and motor neurologic deficits (hemiplegia, hemianesthesia, and hemianopia) [338]. Although many survivors regain some or all cognitive skills soon following a stroke, up to 38% remain cognitively impaired at 3 months [339]. Recovery rates may be as high as 80% within 6 months for stroke survivors, with visual perception and visual memory showing the most improvement and language and abstract reasoning showing the least [340,341]. At 1 and 3 years after a stroke, cognitive impairment is one of the factors most strongly linked with poor physical and mental health status [342]. Cognitive status is an important determinant of post-stroke success. The AHA/ASA recommend that all stroke patients be screened for cognitive deficits before being discharged to home [21].

Following a stroke, it is understandable that patients and their families experience intense emotions. In many cases, the staff's kindness and helpfulness, familial support, and the passage of time allow patients and their families to deal with the grief and other feelings precipitated by the stroke without medication or psychologic therapy. However, approximately 33% of patients experience post-stroke depression, and other mood disorders also manifest in stroke survivors [1,351,352]. In general, psychologic conditions can have a significant impact on the success of rehabilitation. Thus, all patients should be thoroughly evaluated for psychologic disorders as early as possible and on an ongoing basis [21].

A patient's risk for a recurrent stroke is highest during the first year; 14% of survivors have a recurrent stroke within one year after the initial cerebrovascular event, suggesting that secondary prevention is time-critical and should be initiated during the rehabilitation process [375]. After the first year, the chance of recurrent stroke decreases to 4% per year [374]. Because TIA is a precursor to stroke, secondary prevention applies to this category as well. AHA/ASA guidelines, updated 2021, are for prevention of stroke in patients with stroke and TIA [10]. The guidelines focus on four areas: diagnostic evaluation for secondary prevention, risk factor management, treatment in relation to etiology, and systems of care for secondary ischemic stroke prevention. Key take-home points and selected guideline recommendations are discussed in the following sections.