Building Centers of Excellence for the Care of Young Adults With Stroke

Nonstandard Abbreviations and Acronyms

AIS

acute ischemic stroke

PFO

patent foramen ovale

RF

risk factor

Young adults with stroke are a unique subgroup of patients with age‐specific considerations in clinical practice, but there are few US guidelines or broadly implemented management approaches in the United States that tailor care to this population. ¹ , ² As compared with older adults, young adults manifest different acute symptoms, have a broader variety of stroke mechanisms often requiring extensive diagnostic testing, and engage ramifications of stroke prevention, recovery, rehabilitation, and adaptation over longer durations of life expectancy. ³ , ⁴ , ⁵ In the absence of systematic efforts to improve the care of young adults with stroke, many individuals may be misdiagnosed or have a delayed diagnosis initially, undergo incomplete diagnostic investigations, or receive poorly calibrated guidance or therapy aimed at prevention and maximizing recovery.

In 2023, the Stroke and Young Adults Consortium was established to bring clinician experts, patient and caregiver stakeholders, and researchers together to advance the care of young adults with stroke in the United States. Most research studies in the United States define this age group as people aged 18 to 50 at stroke onset (with variation in age thresholds around the world), but we decided as a consortium to include a broader range from ages 18 to 64 (pre‐Medicare eligibility, working age) in research, education, and advocacy efforts. In this Viewpoint, we describe our shared vision for the essential elements needed to build centers of excellence for the care of young adults with stroke given unique challenges they face (Figure).

Figure 1. An example of the experience of stroke and health care delivery for 1 young survivor of stroke.

ACUTE CARE FOR STROKE

Numerous epidemiological studies have identified an increasing incidence of stroke hospitalization for young adults over time (accounting for approximately 15% of hospitalizations for ischemic stroke), but the causes of this trend are not fully understood. ⁴ , ⁶ Recognition of stroke as a disease affecting young adults, including those with few or no traditional vascular risk factors (RFs), is often poor and only recently has become a theme in public health messaging. Although a recent study of thrombolysis use in the Get with the Guidelines registry provides reassurance that young adults with acute ischemic stroke (AIS) are treated with thrombolysis slightly more frequently than older adults, these data do not account for patients who do not receive an initial diagnosis of AIS or who present beyond 4.5 hours from stroke onset. ⁷ Get with the Guidelines data illustrate that young adults are more likely to present later and are less likely to use emergency medical services. ⁸ Young adults (especially with posterior circulation stroke) tend to be misdiagnosed more frequently in emergency departments, and their symptoms more often stutter or progress (despite initial low stroke severity) as compared with older adults. ³ , ⁵ Combining these observations, it is plausible that a substantial portion of young adults with AIS present beyond standard time windows for thrombolysis, present with delay with large vessel occlusions such that the benefit of recanalization may be diminished, they are not recognized as having AIS at all during an initial evaluation, or they do not choose to seek emergency medical care, instead presenting at a later time to primary care.

Some young adult subgroups may require special consideration when weighing the risk–benefit profile of hyperacute therapies. For example, some stroke causes more prevalent in younger populations (eg, Moyamoya, endocarditis) carry a higher risk of hemorrhage with thrombolysis. Other conditions may warrant alternative treatments (eg, exchange transfusion for sickle cell). At a tissue level, the extent to which younger brains respond differently to acute ischemia and treatments is not well established. Young adults undergoing thrombolysis have lower rates of intracranial hemorrhage but a higher risk of malignant edema than older adults. ⁹

With these care gaps in mind, we assert that there are important opportunities for both community and clinician education in the identification and management of acute stroke in young adults. Further research is warranted to tailor acute treatment and monitoring recommendations to this population. We believe these elements are important for centers of excellence to implement:

• Explicitly acknowledge that stroke affects young people in community health education and public health messaging. For example, “Stroke can affect anyone, at any age, at any time.”

• Target health education to communities with a broad age distribution rather than limiting them to elderly communities, and consider focused efforts on young subgroups at high risk for stroke (eg, sickle cell, congenital heart disease).

• Develop nationwide programs to educate children about stroke symptoms and the benefits of healthy diets, physical exercise, and abstinence from tobacco.

• Engage emergency medical services in education on prehospital identification of stroke symptoms, including explicit messaging about stroke as a potential cause of neurological symptoms in young adults. This may improve frequency of prehospital notification for young adults and reduce the likelihood of young people with subtle or transient stroke symptoms choosing to remain at home after emergency medical services evaluation.

• Encourage emergency department clinicians to have a low threshold to activate stroke codes or consult neurology for young patients with potential stroke symptoms, regardless of severity.

• Consider expanding the list of potential stroke symptoms considered for stroke code activation for young adults given a higher rate of atypical symptoms (eg, acute agitation, hyperkinetic movement disorders) and masking symptoms (eg, headache, neck pain, anxiety, seizure, syncope, dizziness, vomiting, etc.).

• Given possible disproportionate long‐term impact of relatively minor stroke‐related disability (as measured by the National Institutes of Health Stroke Scale or modified Rankin Scale) among young adults, reconsider low severity of deficits as an acceptable reason to forego hyperacute treatments for AIS. Individualizing determination of the impact of stroke deficits may help avoid meaningful opportunities to pursue these treatments.

• Promote research efforts targeted at furthering our understanding of how the response to hyperacute ischemia and reperfusion may be unique for young adults, which may influence our understanding of treatment eligibility and monitoring in this population.

Advanced and Informed Diagnostics and Preventive Treatment

Causes of AIS, intracerebral hemorrhage, and subarachnoid hemorrhage are more myriad among young adults as compared with older adults. However, accurate identification of stroke cause in young adults is frequently challenging for many clinicians and health systems. For AIS, classification systems such as TOAST (Trial of Org 10 172 in Acute Stroke Treatment) and ASCOD (Atherosclerosis, Small vessel disease, Cardiac pathology, Other causes, Dissection) emphasize traditional stroke RFs and downplay the causes of AIS that disproportionately affect young adults (eg, nonatherosclerotic vasculopathies; hypercoagulable states; patent foramen ovale [PFO]), potentially influencing the assignment of “cryptogenic stroke” for many young individuals. ¹⁰ Given a high prevalence of atherosclerotic RFs among young adults with stroke in the United States and other countries, many clinicians and clinical researchers attribute AIS in young adults to these RFs that commonly lead to large artery atherosclerosis and lipohyalinotic small vessel disease in older adults. ¹¹ However, the veracity of this attribution of AIS to atherosclerotic RFs may depend on arbitrary age range definitions and associations with specific substrata within the young adult subgroup: the youngest (eg, 18–34) may be more likely to have stroke causes related to nontraditional RFs (eg PFO, migraine, pregnancy) whereas the older substrata (eg, 35–55+) may be more likely to have stroke causes influenced by traditional (atherosclerotic) RFs. ¹²

Further obscuring accurate causal diagnosis is the challenge of titrating and executing appropriate depth of diagnostic testing. Many diagnostic tests for uncommon causes (eg, transesophageal echocardiogram; diagnostic cerebral angiogram; lumbar puncture; hypercoagulability testing) can be costly, invasive, and unavailable outside of tertiary care hospitals. Even when available, waiting in a queue for these tests may prolong hospitalizations; efforts to reduce length of stay may lead to deferral of these studies to the postacute care phase. As a result, many young people with AIS may be discharged with a diagnosis of cryptogenic stroke, largely influenced by the incompleteness of their diagnostic investigation. Some tests that help establish the definitive diagnosis may never be performed if young survivors of stroke are unable to establish outpatient care with a specialist familiar with the broad range of pathologies leading to stroke in young adults. Similarly, young people with intracerebral hemorrhage may have vascular malformations such as arteriovenous malformations or cavernomas that may not be readily identified until diagnostic cerebral angiogram or follow‐up magnetic resonance imaging can be performed. Nevertheless, if comprehensive diagnostic testing is readily available and avidly pursued, the cause of stroke can be readily identified in a majority of cases. ¹³ Another potential pitfall is when an RF only weakly associated with stroke is identified, leading to cessation of further investigation. Particularly in younger individuals, multiple RFs may compound stroke risk; thus, despite identification of a possibly pathogenic factor (eg, oral contraceptive use, PFO), further investigation may be warranted.

When causes of an index stroke are identified, determining optimal prevention requires a high level of precision and often incorporates shared decision‐making with young patients. For example, identification of a PFO in a patient with an embolic stroke benefits from further patient‐ and PFO‐level characterization to understand the likelihood of pathogenesis, the potential benefit of PFO closure, and the presence of concurrent hypercoagulable states. ¹⁴ Patients with cervical artery dissection may variably benefit from antiplatelet therapy versus anticoagulation depending on the morphological characteristics of their dissections, such as if the lesion is occlusive. ¹⁵ Counseling on necessity and duration of lifestyle and medication modifications for certain “provoked” strokes (eg, dissection, reversible cerebral vasoconstriction syndrome) may be particularly meaningful for a physically active individual (eg, athlete) or a patient undergoing medical treatments that may exacerbate reversible cerebral vasoconstriction syndrome risk (eg, serotonin modulating medications, calcineurin inhibitors).

To date, efforts to develop a standardized diagnostic algorithm for young adults with stroke have not been widely adopted. We believe that adopting a set of shared principles may help improve accuracy of diagnosis and prevention treatment for young adults with stroke:

• Although it is unlikely that a “one size fits all” approach will be cost effective for establishing a stroke mechanism for young patients, sufficient depth of diagnostic testing must be pursued to identify early acute and postacute targets for stroke prevention.

• Ascertaining diagnostic yield for individual patients should account for differing probability of stroke causes across the age spectrum. Transesophageal echocardiography is likely a more useful form of cardiac imaging as compared with transthoracic echocardiography for identifying causes of stroke in young adults (eg, PFO, endocarditis, atrial myxomas). Cardiac rhythm monitoring (commonly valuable for detection of atrial fibrillation in older adults) is likely low yield for very young adults with AIS.

• When a potential cause of stroke is identified, the strength of its pathological association should be assessed with further investigation of synergistic factors considered (eg, assess for causes of hypercoagulability in a patient with a PFO).

• Clinicians should embrace the need for precision clinical decision‐making in secondary stroke prevention for young adults with causes of stroke that are more frequent in young adults than older adults. Not all PFOs need to be closed; not all dissections should be treated with antiplatelets; not all hypercoagulable states require anticoagulation. Risk–benefit assessment of prevention treatments must account for decades of potential remaining life expectancy.

• For patients with nonatherosclerotic causes of stroke, identification and management of atherosclerotic RFs should be assertive as atherosclerotic causes of stroke are an important competing risk for future stroke. Counseling of patients should acknowledge differences between the cause of the index stroke and competing atherosclerotic risks, emphasizing low recurrence risks (where appropriate) and methods of effectively reducing atherosclerotic disease risk.

• Promote research on the safety, efficacy, and cost effectiveness of long‐term secondary prevention and surveillance testing in conditions leading to stroke in young adults (eg, cervical artery dissection, intracranial aneurysms, etc.).

STRUCTURED AND MULTIFACETED OUTPATIENT CARE

Common models for postacute care for survivors of stroke tend to be mismatched with the priorities and needs of young survivors. ¹⁶ Large volume centers or stroke clinics with high patient‐to‐clinician ratios tend to distill postacute care into a single posthospitalization clinic visit. Depending on allowed visit duration, this may limit the focus to securing a targeted secondary stroke prevention plan and verifying that rehabilitation needs are being addressed (usually by another provider). For many young survivors of stroke, this limited scope is not enough to help them rebuild their lives. Late complications after stroke frequently emerge weeks, months, and years following stroke onset: these neurological sequelae (cognitive impairment, central pain, epilepsy, movement disorders, spasticity, sleep disorders) and psychosocial sequelae (anxiety, depression, irritability, posttraumatic stress, sexual dysfunction, suicidal ideation) are barriers to recovery and are detrimental to quality of life. ¹⁷ There are no current guidelines supporting screening for most of these conditions (which may disproportionately affect young survivors of stroke due to higher frequency and longer duration of impact), and there are no widely adopted practices aimed at addressing these. Young survivors often strive to regain prestroke responsibilities (caregiver roles, employment) and abilities (driving) that are critical for independence, familial roles, and community involvement. Young survivors often clash with their partners (on issues intersecting with stroke recovery), leading to high rates of divorce and separation. Many clinicians are not trained or equipped to guide survivors of stroke or caregivers through these challenges.

Significant gaps exist in transitions of care from pediatric to adult medicine for pediatric survivors. An analysis from the National Survey of Children's health reported that only 17% of children with chronic medical conditions received guidance on transition planning. ¹⁸ For a pediatric survivor of stroke, these gaps can have devastating consequences, particularly for children with ongoing disability who are leaving home. Ensuring a structured plan for the myriad realms in which survivors of stroke need support (eg, medication adherence, mobility, late complications after stroke) often requires lengthy lead‐in time and collaboration between pediatric and adult providers, in conjunction with the patient and caregivers, to ensure optimal care coordination and transition readiness.

We believe that centers providing optimal postacute care for young survivors of stroke are structured with the following principles:

• Clinicians and clinical programs explicitly acknowledge young survivors of stroke as a unique subgroup. This acknowledgement may manifest as a clinic dedicated to young survivors, longer appointment times, young survivor‐specific support groups (local or regional), or educational materials and other resources specific to young survivors and their caregivers.

• Coordinated, multidisciplinary care is essential for optimal diagnosis and prevention, as well as rehabilitation, adaptation, and survivorship. Current stroke programs for young survivors develop strong connections to other neurological, medical, surgical, and rehabilitation disciplines.

• Clinicians providing care for young survivors are adept at identifying and addressing late complications after stroke to attenuate or remove these barriers from the recovery trajectory of survivors.

• Clinical programs address the well‐being of young survivors, assigning priority to improving quality of life and aiding survivors in achieving their role‐ and responsibility‐related goals. Use of patient centered measures such as the Young Stroke Questionnaire may provide more age‐appropriate targets for interventions. ¹⁹

• Clinical programs aid survivors by supporting caregivers, including with family caregiver training.

• Both adult and pediatric centers take into special consideration the complex needs of pediatric stroke survivors transitioning to adulthood with a structured process to address ongoing and anticipated poststroke issues.

• As young adults with stroke have high rates of premature mortality, focused efforts on identifying and addressing causes of early mortality (eg, cardioaortic disease, recurrent stroke, malignancy) must be prioritized. ²⁰

• Understanding that these priorities take time, clinical programs may develop methods of providing longitudinal care or developing systems of long‐term follow‐up to continue to aid young survivors as new health considerations emerge (eg, pregnancy after stroke, advancing into middle age).

Although the state of science and guidelines related to young adults with stroke are not yet at a point where certification or regulation is feasible to direct young people with stroke symptoms or young survivors to specific centers, we submit this shared vision of principles that clinicians and centers can adopt to improve the care of young adults with stroke throughout the United States. We acknowledge that there is variability in the availability of resources that we highlight as essential to achieving excellence, and that the feasibility and cost‐effectiveness of these approaches are currently unknown. As these centers are developed, research on their implementation and impact will help address these unknowns.

Sources of Funding

None.

Disclosures

None.

Supporting information

Data S1