Neurology Concepts: Young Women and Ischemic Stroke: Evaluation and Management in the Emergency Department

Abstract

Objective

Ischemic stroke is a leading cause of morbidity and mortality worldwide. While the incidence of ischemic stroke is highest in older populations, incidence of ischemic stroke in adults has been rising particularly rapidly among young (e.g. premenopausal) women. The evaluation and timely diagnosis of ischemic stroke in young women presents a challenging situation in the emergency department, due to a range of sex-specific risk factors and to broad differentials. The goals of this concepts paper are to summarize existing knowledge regarding the evaluation and management of young women with ischemic stroke in the acute setting.

Methods

A panel of 6 board certified emergency physicians, 1 with fellowship training in stroke and 1 with training in sex and gender based medicine, along with 1 vascular neurologist were co-authors involved in the paper. Each author used various search strategies (e.g PubMed, Psycinfo, and Google Scholar) for primary research, and review articles related to their section. The references were reviewed and evaluated for relevancy and included based on review by the lead authors

Results

Estimates on the incidence of ischemic stroke in premenopausal women range from 3.65 to 8.9 per 100,000 in the United States. Several risk factors for ischemic stroke exist for young women including oral contraceptive (OCP) use and migraine with aura. Pregnancy and the postpartum period (up to 12 weeks) is also an important transient state during which risks for both ischemic stroke and cerebral hemorrhage are elevated, accounting for 18% of strokes in women under 35. Current evidence regarding the management of acute ischemic stroke in young women is also summarized including use of thrombolytic agents (e.g. tPA) in both pregnant and nonpregnant individuals.

Conclusion

Unique challenges exist in the evaluation and diagnosis of ischemic stroke in young women. There are still many opportunities for future research aimed at improving detection and treatment of this population.

Introduction

In the United States, stroke is the 5^th overall leading cause of death and the 4^th leading cause of death for women, with over sixteen million first time strokes occurring annually worldwide.¹ In the U.S., over 500,000 new ischemic strokes are diagnosed each year with the annual financial impact of stroke approaching 33 billion dollars.² In addition, though the incidence of ischemic stroke is highest in older populations,³ it has been increasing in the young.⁴

The recognition and diagnosis of ischemic stroke in pre-menopausal (young) women represents a challenging scenario in the emergency department (ED). In addition to incorporating the presence of sex-specific risk factors for stroke (e.g. oral contraceptive use, history of pre-eclampsia), there is a broad differential diagnosis for neurological symptoms in young women besides stroke such as drug toxicity, the acute onset of demyelinating disease, and complicated migraine. The timely evaluation, diagnosis, and management of ischemic stroke in young women is particularly important for young women given the potential for many years of either disability or productivity. Emergency physicians need to be vigilant because a subset of these patients may benefit from time sensitive treatments such as reperfusion therapies. ^5,6

The goals of this concepts paper are to provide a succinct overview and update on existing knowledge regarding the epidemiology, diagnostic consideration, and management strategies for young women with suspected ischemic stroke. For the purpose of this paper, we define “young women” as pre-menopausal women, in recognition of the unique pre-menopausal risk factors (e.g. oral contraceptive use, pregnancy, endogenous hormones) present in these patients and the changes in risk and of etiology of stroke in women following menopause.⁷ By integrating current existing knowledge on young women and stroke, we hope to aid emergency clinicians in their ability to identify and optimize care for this population of high risk patients in the ED.

Epidemiology

Estimates on the incidence of ischemic stroke in premenopausal women range from 3.65 to 8.9 per 100,000 in the United States and Continental Europe.^8,9 Overall, the rate of young people (under the age of 50) with ischemic stroke is estimated to be approximately 50,000 new cases annually in the US.² Acute hospitalization rates for young women with ischemic stroke appear to have increased between 1995 and 2008,¹⁰ with increases particularly significant in women aged 15 to 44.¹¹ Additionally, while the overall incidence of both ischemic and hemorrhagic stroke is lower in this age group compared to older adults, the cost of hospitalization for stroke is higher for young patients compared to adults aged 65 and older. The average hospitalization cost for all strokes (ischemic and hemorrhagic) has risen from $19,000 to over $26,000. Younger adults, both women and men, with strokes have longer average lengths of stay at 7.8 days, compared to 5.2 days for adults aged 65 and older.¹¹ The reason for this counterintuitive finding is not well-understood. More extensive diagnostic testing for uncommon conditions such as carotid dissection may contribute to longer length of stay among younger patients.

Using the TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification system for subtypes of ischemic stroke, the etiologies of ischemic strokes for women and men across all ages (to be differentiated from hemorrhagic strokes including subarachnoid hemorrhage) are large-artery atherosclerosis (embolus/thrombosis), cardio-embolism (e.g. atrial fibrillation as well as other processes such as valvular disease or paradoxical emboli), small-vessel occlusion (lacunae), stroke of other determined etiology (e.g. cervical artery dissection, hematologic disorders), and stroke of undetermined etiology.¹² The leading etiology of acute ischemic stroke in young adults is atherosclerosis, which reflects the growing epidemic of cardiovascular disease in younger populations. Among those without risk factors for atherosclerotic disease, however, especially in those younger than age 40, non-atherosclerotic vasculopathies (e.g. cervical arterial dissection), cardio-embolism, and hematological disorders such as sickle cell disease are more likely.^13–15 During pregnancy, the leading cause of ischemic stroke is arterial occlusion, from artery-to-artery emobolization or cardioembolic events, most often presenting in the third trimester and postpartum periods.^16–18 Unexplained etiologies account for 21–31% in young adults, similar to the proportion of cyptogenic stroke in elderly patients.

There is also growing epidemiological evidence demonstrating an increasing incidence of transient ischemic attacks (TIA) and ischemic strokes in young persons over time.^15,19,20 These trends may be reflective of the increasing burden of traditional metabolic stroke risk factors in the young such as type 2 diabetes, hyperlipidemia, and obesity, which have been reported in higher income countries.^21,22 Additionally, tobacco use is common in young adults, and rates of substance abuse have increased over time. ^22,23 Tobacco use, particularly in younger patients, has been associated with increased risk for ischemic stroke (RR= 1.9 overall, RR=2.9 for patients under age 55),²⁴ with some data suggesting that women smokers may actually have a higher relative risk of developing cardiovascular disease compared male smokers.²⁵

Risk Stratification

In young women, multiple stroke risk factors exist that are either unique to or more prevalent in women including use of exogenous hormones, migraines with aura, history of pre-eclampsia, and pregnancy. ^26–30 (Table 1)

Table 1:

Risk Factors Associated with Ischemic Stroke in Pre-Menopausal Women

• Exogenous Hormones Use (Oral contraceptives) • Migraines with Aura • Pre-eclampsia (Current or History of) • Current or recent pregnancy • Tobacco Use • History of Diabetes • Autoimmune and vasculitis disorders

Oral Contraceptive Use

It is estimated that 1 in 6 women of reproductive age use oral contraception.³¹ The potential association between ischemic stroke and oral contraception (OCP) was raised as early as 1962, shortly after the first availability of OCPs.³² In the 1970s when high dose estrogen OCPs were commonly used, the risk of ischemic stroke was estimated to be increased nearly 5 times for women on OCPs.³³ In subsequent years, as the estrogen content of OCPs has decreased, the magnitude of the association between ischemic stroke and OCP has lessened, though it still persists. A recent Cochrane systematic review revealed a 1.6-fold increased risk of ischemic stroke or myocardial infarction among women taking combination oral contraceptives, with the highest risk for pills with >50 micrograms of estrogen.³⁴ Tobacco use appears to confound the risk of stroke associated with OCPs; women who smoke, take OCPs, and have a history of migraine have a nearly 9-fold increase in risk of stroke compared to women without such risk factors.^35,36 Other factors such as hypertension, diabetes, obesity, and hyperlipidemia are relevant in accelerating the risk with OCP use.³⁷ Additionally, the use of exogenous estrogen in transgender women must be considered as a potential risk factor for ischemic stroke when evaluating such patients in the ED setting.³⁸

Migraine

A history of migraine headaches with aura is an additional risk factor for ischemic stroke to which emergency providers should be attuned during their evaluation of patients with presumed migraine or suspected stroke, given that the frequency of migraine is estimated to be nearly 3 times more common in women than men. ^39,40 Multiple cohort and case control studies have demonstrated an association between migraine with aura and acute ischemic stroke.⁴¹ Although migraine treatment medications, co-existent patent foramen ovale (PFO), and vasospasm have been implicated in the pathophysiology of migraine and stroke, more research is needed to elucidate the mechanisms behind such potential links between the two.^39,42

Risks Specific to Pregnancy

Pregnancy and the postpartum period is an important transient state during which the risks for both ischemic stroke and cerebral hemorrhage are elevated. Some literature estimates that pregnancy among young women accounts for approximately 18% of strokes in women younger than age 35.⁴³ Despite this risk, the incidence remains low, ranging from 21–34.2 per 100,000 pregnancies among patients age 25 to 34 years, inclusive of ischemic and hemorrhagic events.^16,44 The highest risk of stroke during pregnancy occurs during the peri-partum periods (the last month of pregnancy and first 12 weeks after delivery), with a relative risk for ischemic stroke of 8.7 and a relative risk of hemorrhagic stroke of 28.7.^45,46 Risk of ischemic and thrombotic events is also elevated during the peri-partum period, with increased risk for thrombotic (both arterial and venous) events (RR: 3.0 (95% CI, 1.6 to 4.5).⁴⁷

Most ischemic strokes that occur in pregnancy are a result of atherosclerosis, artery-to-artery thromboembolism, or cardiac embolism other than atrial fibrillation.⁴⁸ Nonetheless, other etiologies are notable for their association with pregnancy. One of these, dural venous sinus thrombosis (DSVT) or cerebral venous thrombosis (CVT) is rare but occurs more commonly in the third trimester, particularly in the 6- week postpartum period and may also present with hemorrhage (e.g. nearly 30–40% of DSVT/CVT present with intracerebral hemorrhage)^49–51. This elevated risk continues approximately one month after delivery. ^52,53 It occurs in approximately 1 of 10,000 deliveries in high-income nations but has higher incident rates in the developing world.⁵⁴ The risk of carotid or vertebral dissection is also elevated in the peri-partum period. The incident rate is not well defined in pregnancy but appears to occur more frequently in the post-partum period.⁵⁵ This is likely because the antiangiogenic environment in the peripartum period causes maternal endothelial dysfunction, which makes the endothelial layer susceptible to intimal rupture.⁵⁶ Patients commonly have an additional prothrombotic condition such as a Factor V Leiden mutation.⁵⁷ Finally, postpartum angiopathy is an additional rare but potential complication of pregnancy that leads to cerebral arterial constriction and brain ischemia.⁵⁸

The need for transfusion due to hemorrhage around the time of delivery and postpartum infection is also strongly associated with increased odds of stroke. In one study, the odds ratio of developing a stroke associated with postpartum infection was 25 (95% CI 18 – 34).⁴⁴ Finally, stillbirth and preterm delivery are additionally associated with increased risk of ischemic stroke.⁵⁹

Pre-eclampsia

Pregnancy-related hypertension is an important contribution to overall ischemic and hemorrhagic stroke risk in young women both during pregnancy and later in life.^44,45 Up to 12% of all pregnancies are complicated by gestational hypertension, pre-eclampsia, or eclampsia.⁴⁸ Both several single center case series as well as larger cohort studies have noted that pre-eclampsia/eclampsia, alongside underlying cerebrovascular malformation, were among the most commonly identified etiologies of pregnancy-associated stroke, the majority of which were hemorrhagic.^18,46,60,61 Larger cohort studies have also confirmed this association; analysis of data from the Nationwide Inpatient Sample reported that pre-eclampsia was associated with a 4-fold increase in stroke during pregnancy (OR: 4.4 95% CI 3.6–5.4).^16,60 Additionally, posterior reversible encephalopathy syndrome (PRES) may be a complication of pre-eclampsia and eclampsia and can result in stroke-like symptoms, in addition to ischemic stroke and intracerebral hemorrhage.^62,63

While women with pre-eclampsia were historically thought of being out of the “danger zone” after the peri-partum period, risk of stroke and cardiovascular disease in patients with pre-eclampsia appear to persist long after the peri-partum period. A meta-analysis of studies examining risk of cardiovascular disease and ischemic stroke later in life found that women with a history of pre-eclampsia had nearly double the risk for ischemic stroke (RR: 1.81; CI: 1.45–2.27), almost four times the risk of developing hypertension (RR: 3.70; CI: 2.70–5.05), and over 2 times the risk of developing ischemic heart disease (RR: 2.16; 1.86–2.52) at 10 year followup.⁶⁴

In summarizing the approach to evaluating pregnant and peri-partum patients in the ED, providers should be aware of the elevated risk for ischemic and hemorrhagic stroke associated with pregnancy that may remain elevated up to 12 weeks postpartum. Information regarding blood pressure, delivery date, as well as events such as transfusion and infection around time of delivery should be noted. A history of pre-eclampsia should be collected in young women by clinicians regardless of pregnancy status. Finally, with regards to radiographic imaging in the evaluation of stroke during pregnancy, the use of non-ionizing radiation methods such as Magnetic Resonance Imaging (MRI) without gadolinium remain the preferred imaging option in pregnancy as risks to the fetus are minimized⁶⁵. However, if clinical suspicion is sufficiently high for acute stroke, the benefits of identifying a life threatening condition in the mother with the use of ionizing radiographic methods such as CT imaging may outweigh potential exposure of fetus to radiation and should be considered. ⁶⁶

Other Risk Factors

In addition to the aforementioned risk factors, other sex differences in stroke may be present. Traditional stroke factors such as diabetes may impact women more severely than men. A recent meta-analysis of risk of stroke and diabetes found that the pooled adjusted RR of stroke associated with diabetes was greater in women compared to men (RR 2.28; 95% CI: 1.93–2.69 in women compared to RR 1.83; 95% CI 1.60–2.08 in men).⁶⁷ Young women also have a significantly higher prevalence of autoimmune disorders and vasculitis disorders which may lead to hypercoaguable states and elevated ischemic stroke risk.⁶⁸ These include conditions such as Takayasu’s arteritis, systemic lupus erythematosus, Churg-Strauss, antiphospholipid antibody syndrome, and more rarely Sneddon’s Syndrome (a progressive noninflammatory arteriopathy associated with skin rash and ischemic stroke risk) and Susac’s Syndrome (an autoimmune condition resulting in encephalopathy, branch retinal artery occlusion and hearing loss).^69,70 Idiopathic moyamoya disease has also been increasingly recognized as a cause of ischemic stroke in younger women more commonly than in young men.⁷¹ Finally, clinical depression, a condition more prevalent in women,⁷² has been found to be associated with increased risk of stroke morbidity and mortality.⁷³

Differential Diagnosis

One of the great challenges in the evaluation of young women for potential acute ischemic stroke is the presence of a broad differential diagnosis for such patients presenting in the ED. The diagnostic challenge is at times particularly difficult in young women, in whom providers may suspect stroke less often compared to other cohorts.⁷⁴ Rare forms of ischemic stroke are more common in young women (e.g., up to 10% of strokes in younger patients are caused by carotid or vertebral artery dissections, a more rare cause of stroke in older populations),⁶⁹ and the breadth of stroke mimics in young women (compared to men) presenting to the ED is large and diverse.⁷⁰ (Table 2)

Table 2:

Possible Stroke Mimics

• Migraine • Seizure • Space occupying lesion (e.g. brain mass, abscess) • Peripheral Vertigo • Multiple Sclerosis (optic neuritis) • Infection (e.g. meningitis, encephalitis) • Vasculitis • Blood Dyscrasia (e.g. sickle cell) • Intoxication • Toxic-Metabolic process (e.g. hypoglycemia, hyponatremia) • Psychogenic Etiology/ Conversion Disorder

Retrospective data has found frequent stroke mimics in young adults, and young women in particular, including migraines with aura, multiple sclerosis, (often optic neuritis⁷⁵), seizures, dizziness (e.g. acute vestibular syndrome), infections (in particular, urinary tract infections), and psychogenic etiologies such as conversion reaction.^76,77 Migraine with aura is a particularly disconcerting phenomenon not only because of the overlap of symptomatology with ischemic stroke but because migraine with aura itself appears to be an independent risk factor for ischemic stroke.⁷⁸ A history of migraine with aura increases the risk of ischemic stroke in young women more than three-fold, with up to 40% of ischemic strokes in women with migraine with aura developing directly following a migraine attack.⁷⁹ This may be due to a combination of vasospasm, endothelial dysfunction, hypercoagulability, and oxidative stress, or even due to the relatively high incidence of patent foramen ovale in migraine patients with aura compared to migraine patients without aura.⁷⁰

A complete neurologic review of systems and exam is critical in the evaluation of patients with either suspected stroke or stroke mimic. Posterior circulation strokes also pose an especially challenging diagnosis in young women and have the potential to be under-diagnosed. A case-series of patients with cerebellar infarctions initially misdiagnosed in the ED found that half of such patients were under the age of 50 and a significant majority of patients had incomplete neurological exams performed or documented.⁸⁰ Another case series of young women with arterial dissection or posterior circulation strokes found that patients were often initially diagnosed (and discharged) with a diagnosis of positional vertigo.⁷⁴ The use of some bedside screening exams such as the head impulse, nystagmus type, test of skew (HINTS) has been found to be sensitive and specific for distinguishing a peripheral cause from a central cause of vertigo and may be of utility at the bedside in evaluating young women with vertiginous symptoms in the ED, although initial validation studies were performed by neurologists and opthamologists and its utility when done by emergency physicians is unclear.^81–83 For emergency providers, brain and vessel imaging such as MRI or CTA imaging may provide critical information regarding visualization of the posterior circulation and identification of vessel lesions such as carotid dissection.

Future work studying the utility of bedside physical exam assessments such as the HINTS tool coupled with their association with other diagnostic studies such as MRI, CT or other vascular imaging may provide more sensitive and specific tools to help distinguish ischemic stroke from its myriad of mimics. In tackling the broad differential for potential ischemic stroke, aspects of the history and physical, such as distribution of lesion and time course, may also prove useful in distinguishing stroke from mimics.⁷⁷ Though more data is needed to understand how clinical features and/or presenting symptoms might be used to systematically differentiate mimics much as migraine with aura from ischemic stroke, some suggest that MR imaging may help differentiate these diagnoses.⁸⁴ In addition, instruments designed to help distinguish stroke mimics in the acute setting may also be of potential use for emergency physicians. For example, the Recognition of Stroke in the Emergency Room (ROSIER) is a stroke recognition tool which has been validated for use in the ED in the initial differentiation of suspected acute stroke versus stroke mimics.^85,86 Retrospective and prospective studies using ROSIER identified complex migraine with aura (33.9%)⁸⁷, seizures (23%), syncope (23%), and sepsis (10%) as among the most common stroke mimics. Prospective work in 173 suspected stroke cases found a sensitivity of 92% and specificity of 86% with positive predictive value of stroke of 88%.⁸⁵ Attempts, however, to replicate these results in the ED have found lower specificity rates (e.g. 41%) in samples outside the U.S.,⁸⁸ suggesting that additional work is needed to clarify its use across different ED settings and practices.

ED Management

Decisions about time-sensitive therapies including intravenous (IV) tissue plasminogen activator (tPA) and mechanical thrombectomy are challenging when managing young women with stroke symptoms. Because of stroke mimics that are more common in young women than other demographic groups,^1–3 diagnostic uncertainty may be more pronounced and has the potential to lead to uncertainty about the use of IV tPA and/or endovascular therapies. Multiple observational studies, however, have shown that rates of symptomatic intracranial hemorrhage in patients with stroke mimics that received IV tPA are less than one percent, much lower than rates of symptomatic intracranial hemorrhage among patients with confirmed acute ischemic stroke.^89–91Rates of other adverse effects from tPA including angioedema are extremely rare as well.⁹²

Providers should also be aware of potential gender disparities in the treatment of stroke patients. Though contributing factors are not entirely clear, past literature shows that women are less likely to receive IV tPA.^93,94 Reasons for this disparity are unknown, but possible contributors include gender differences in stroke presentation and potential implicit bias of providers. Overall eligibility for tPA has not been shown to be a contributing factor.⁹⁵

Data on the use of endovascular therapy in young women are more sparse, as the recent randomized controlled trials of endovascular therapy for acute ischemic stroke were comprised of mostly patients > 50 years old.⁸ For example, the ESCAPE trial had just over 50% women but the median age was 70.⁸ Data does indicate, however, that younger age is associated with better 90-day functional outcomes after endovascular therapy.⁹⁶ Parallel to gender disparities in use of IV tPA, it has also been shown that women are less likely to receive angiography for acute stroke,⁹⁷ even though women may derive greater benefit from such therapies.⁹⁸ Given overall convincing data from multiple RCTs of endovascular therapy for acute ischemic stroke,⁹⁹ evaluation for large vessel occlusions using CT or MR based vessel imaging should be utilized in young women in appropriately selected patients to identity those who may benefit from endovascular therapy. It is also unknown whether patient selection strategies for thrombectomy should differ by patient sex given smaller caliber vessels in women compared to men. To advance knowledge of sex differences in endovascular therapy, future studies could report outcomes by both sex and by age group”.

tPA in Pregnancy

Though data is limited on the treatment of pregnant patients suffering acute ischemic strokes with tPA, observational evidence suggests that pregnant women can be safely treated with tPA and that treatment should be considered in pregnant women presenting with disabling strokes. Recent American Heart Association and American Stroke Association guidelines offer a Class IIb recommendations that IV tPA may be considered for the treatment of acute ischemic stroke in pregnancy when the anticipated benefits of treatment of moderate to severe stroke outweigh the anticipated increased risks of uterine bleeding.¹⁵ Though there are no randomized control trials investigating the safety and efficacy of IV tPA in pregnant women with acute ischemic stroke, several case reports and one cohort study of women treated with tPA in pregnancy have found similar outcomes to nonpregnant women treated with tPA with respect to rates of discharge-to-home, bleeding complications and symptomatic intracranial hemorrhage.^2,5–11 Ultimately, the decision to treat pregnant women with acute ischemic stroke should be made on an individualized basis with consideration for risks versus benefits of treatment.

Outside of considering acute interventions for stroke, other management strategies that EM physicians should consider in young women with suspected stroke center on risk factor modification. Though many risk factors for this patient demographic are not modifiable, EM physicians should strongly consider smoking cessation counseling in young women, especially those with concurrent risk factors including migraine with aura and/or use of oral contraceptives.¹⁰⁰ Such counseling strategies should be built into protocols for ED observation units that treat patients with suspected stroke or TIA. A future area of research for emergency providers could focus on the development of risk stratification scores for young women, especially with regard to smoking status, oral contraceptive use, history of pre-eclampsia, and women with migraine with aura, in order to improve the identification of those patients at greatest risk for stroke.

Disposition of Young Women with Suspected Ischemic Stroke

In young women in whom there is moderate or high suspicion for ischemic stroke and/or disabling deficit, patients should be dispositioned similarly to other stroke patients (e.g. inpatient admission to monitored setting or stroke service). However, for other patients for whom suspicion of ischemic stroke is low, admission may not be clinically justified or practical. Current National Stroke Association TIA guidelines recommend that hospitalization be “considered” for patients presenting with a first transient ischemic attack within the past 24 to 48 hours; it is “generally recommended” for patients with crescendo transient ischemic attacks, duration of symptoms greater than 1 hour, symptomatic carotid stenosis greater than 50%, a known cardiac source of embolus or a known hypercoagulable state.¹⁰¹ Emergency clinicians are increasingly placing TIA patients in observation care for expedited evaluation rather than inpatient care.¹⁰² Placement in observation is associated with reduced cost and length of stay compared to admission and may be a consideration for certain patients with TIA or minor stroke.^103,104

Regardless of inpatient versus outpatient management of TIA, National Stroke Association guidelines recommended timely management of all such patients for possible brain and vascular imaging, and an early assessment and implementation of secondary prevention strategies to prevent further ischemic events as assessed in followup.^101,105,106 One area of future research, may be the examination of the use of urgent neurology outpatient follow-up or specialized TIA/stroke clinics in the disposition of young women for whom risk of acute ischemic stroke is considered low. Such a strategy could potentially not only reduce adverse 90-day neurological outcomes in young women with potential TIA or minor stroke but may also reduce unnecessary healthcare expenditures associated with inpatient admission and workup.^104,107,108

In summary, as with all patients with suspected ischemic strokes, EM physicians should consider the use of IV tPA and imaging for large vessel occlusions in young women with symptoms consistent with acute ischemic stroke. Shared decision making may be an effective clinical tool, using information including the known low risk for post-thrombolytic symptomatic intracranial hemorrhage. Future research should focus on developing clinical tools and/or strategies for use in the hyperacute period that could improve the ability to select patients in this demographic at higher risk for stroke and who might benefit from IV tPA. Though it remains to be seen, such tools could include validated sex-specific clinical decision rules that incorporate sex-specific risk factors.¹⁰⁰

Limitations

While the goal of our concepts paper was to introduce and summarize current approaches to the evaluation of young women and ischemic stroke, our piece was not a comprehensive literature review. Each author used various search strategies for articles related to their section, and the references were reviewed and evaluated for relevancy and included based on review by the lead authors. Given the multiple clinical questions reviewed in this concepts piece on young women and stroke, though, we did not perform a comprehensive literature review and had a broad timeframe for studies and reviews used in this paper. As such, there may have been some studies relevant to this paper that were not included. Future work following up with more sub-focused questions and systematic methodological approaches may provide additional insight into the management and approach of young women and ischemic stroke.

Conclusion/Future Directions

Ischemic stroke is a devastating condition with significant morbidity and mortality. While traditionally a disease of older patients, the impact of ischemic stroke in young women is considerable, with increased risk of recurrent stroke, and long term negative physical and psychological impairments to quality of life.¹⁰⁹ The aim of our concepts paper was to provide emergency providers with a foundation of knowledge regarding ischemic stroke in young women and to address the unique challenges in the evaluation and diagnosis of ischemic stroke in young women. Multiple opportunities for future research aimed at improving detection and treatment of this population remain. Work aimed at creating the design/ application of clinical decision rules, educational campaigns designed to educate young women and EM providers, and consideration of preventive strategies that might be applied in the ED (i.e. young women with HTN, smoking, obesity etc.), may ultimately lead to interventions that can improve outcomes in women with ischemic stroke.

Ultimately, a multi-disciplinary approach aimed at improvements in the identification and care of young women will increase our understanding of the pathophysiology of ischemic stroke as well as improve outcomes for patients served in the emergency department.

Figure 1:

Images from a 23 y.o. female with 2 weeks of neck pain and unilateral earache who then for 3 days had “subtle dizziness” progressing to vertigo/ataxia on morning of presentation. The patient progressed to becoming obtunded in the ED after evaluation by the stroke team. She had a history of seeing a chiropractor 3–4 week prior for mild neck pain. Panel A: Left vertebral artery occlusion from dissection. Panel B: mid basilar occlusion. Panel C: left brainstem and bilateral cerebellar/thalamic restriction of diffusion on MRI consistent with ischemia.