Opinion statement
Optimal diagnosis and management of stroke in young adults benefit from a multidisciplinary team, including a vascular neurology specialist. In addition to the “standard” vascular risk factors including smoking, hypertension, diabetes, and hyperlipidemia, one needs to consider alternative etiologies including substance abuse, carotid/vertebral artery dissections, and rare genetic conditions among others. Once a young patient is determined to have had a stroke, the next question a clinician should ask is why did this patient have a stroke? A “heart to head” diagnostic approach is recommended. A thorough history is performed, including a detailed family history with specific annotations on each family member. A thorough physical examination is necessary including a careful evaluation of the patient’s general appearance, noting any joint laxity, and/or abnormalities of the skin, eyes, and heart. Findings across multiple organ systems in the patient and/or their family may indicate a genetic etiology. After an initial head CT rules out hemorrhagic stroke, additional testing should include a brain MRI, neck and cerebral vascular imaging (e.g., CTA for head and neck), transthoracic echocardiogram with a bubble study, telemetry monitoring, basic risk factor blood work (e.g., lipid panel, hemoglobin A1c, TSH, ESR, CRP, RPR, HIV, and toxicology screen), and, when appropriate, sickle screen and pregnancy test. There should be a low threshold to obtain blood cultures or a lumbar puncture. The acute treatment of ischemic stroke in young adult patients does not differ from treatment of older adults, using intravenous alteplase within 4.5 h, assuming no contraindications. In suspected proximal large artery occlusive disease, interventional clot extraction procedures should be employed in patients deemed eligible. Long-term secondary prevention strategies aimed to reduce recurrent stroke risk by targeting and modifying vascular risk factors should be instituted. The mainstay of preventative therapy is aspirin for most etiologies; however, for atrial fibrillation, anticoagulation is recommended. Statin therapy is another pharmacologic intervention recommended in most stroke patients. Other measures employed are blood pressure reduction, smoking cessation, optimal glucose control in diabetic patients, the initiation of a healthy diet and regular exercise, and lastly, substance abuse counseling in appropriate patients.
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Introduction
Stroke is among the most common and devastating diseases in the USA and worldwide. It is the leading worldwide cause of adult disability and is the fourth leading cause of death in the USA [1, 2••]. Stroke is broadly defined as a brain injury resulting from a vascular insult and can be broadly classified into two primary types, ischemic and hemorrhagic. Ischemic strokes result from insufficient blood flow to the brain leading to neuronal damage and cell death. Hemorrhagic strokes result from blood vessel rupture leading to bleeding into the brain tissue, termed an intracerebral hemorrhage, or into the surrounding brain regions, with such strokes named based on the bleeding location, including subarachnoid, intraventricular, epidural, and subdural hemorrhages.
The definition of “stroke in young” has not been uniformly implemented across many studies, with age ranges from < 44to < 55 years old. At this time, the most accepted definition is any stroke in an adult 18–49 years of age. In recent years, a concerning trend has emerged in which younger patients are having more strokes. Multiple studies have demonstrated that US stroke hospitalizations have increased for patients < 50 years old [3•, 4, 5, 6], this despite an overall decline in stroke hospitalizations and stroke-related death in recent years [3•, 4, 7,8,9,10]. Stroke in the young is particularly significant given its tremendous social and economic impact, as patients are left disabled during their peak years of productivity [11]. From an economic standpoint, the burden of young stroke on the healthcare system is thereby also growing. Notably, one study including both young and old patients recently estimated the cost (in US dollars) per hospital stay for patients affected by stroke demonstrating cost differences across stroke subtype as primarily driven by length of stay and stroke severity, ischemic stroke ($34,886), subarachnoid hemorrhage ($146,307), and intracerebral hemorrhage ($94,482) [12,13,14].
Young patients with stroke shift the diagnostic paradigm in clinical practice, as the etiology of ischemic stroke is different for young patients compared to older patients. The general trend with age is that the proportion of strokes due to large artery atherosclerosis and small vessel disease increase with age [15,16,17]. The most common identified causes of ischemic stroke in the young in the Helsinki Young Stroke Registry were cardioembolic (18.7%) and cerebral artery dissections (15.5%), small vessel disease (13.9%) and large artery atherosclerosis (8.4%) with a significant amount (33.1%) having an undetermined etiology [16, 18]. Although they were less prevalent, strokes resulting from large artery atherosclerosis or cardioembolic sources have a higher risk of death compared to other etiologies [19, 20]. One study demonstrated a 17-year mortality rate of 60% in large artery atherosclerosis in young patients [19]. Other factors associated with worse outcomes included cardiac disease and previous stroke [21], coronary artery disease [22], active tumor [22], excessive alcohol consumption [22], DM [20, 23, 24], high initial NIHSS score [25], male gender [21], and older age [20, 21]. As with stroke at older age, mortality is highest in the first month and is due to vascular reasons (recurrent stroke, cardiac or aortic causes) a majority of the time. After the first year, the mortality rates decrease significantly to 1.4–1.9% annually [20]. Younger patients with large ischemic stroke are more susceptible than older patients to malignant edema requiring hemicraniectomy and should be followed very closely through peak edema, typically up to 5 days post stroke onset.
The diagnostic workup
The strategy employed in all ischemic stroke patients is to evaluate from “heart to head”. This provides a framework for clinicians evaluating all stroke patients, inclusive of young onset stroke patients. The strategy focuses on evaluation for etiology of the stroke, which in turn, drives the immediate and long-term secondary prevention therapeutic strategies. The “heart to head” approach is usually rapidly done during an inpatient stroke evaluation and includes telemetry heart monitoring, echocardiography, CTA or MRA imaging of the head and neck vessels, and a MRI of the brain. Occasionally, patients will be referred to clinic settings after being discovered to have minor strokes, but the same diagnostic approach is applied in the outpatient setting.
The brain/head
The hyperacute phase of stroke management and evaluation is done within the first few minutes of the patient arriving to the hospital or emergency department. After the airway, breathing and circulation have been deemed to be stable; the first major steps in the evaluation can performed in parallel, including the neurologic history, NIHSS, and a non-contrast CT brain to rule out hemorrhagic stroke. More recently, patients with clinical symptomology suggestive of large vessel occlusion with cortical signs (i.e., gaze preference, aphasia, and neglect) may also undergo a stat CTA of the head and neck; this is to evaluate for interventional thrombectomy candidacy which will be discussed in a later section. After the hyperacute phase of evaluation and treatment including IV tPA in eligible patients, the aforementioned “heart to head” approach is continued. One of the major diagnostic tests performed is a brain MRI. Brain MRI illustrates the area(s) of ischemia on DWI, ADC, and FLAIR sequences and can be helpful in determining stroke etiology. For example, ischemic stroke affecting multiple vascular territories is suggestive of cardioembolic etiologies or vasculitis. The appearance on MRI may also give diagnostic clues to more esoteric causes of strokes, including mitochondrial encephalopathy lactic acidosis and stroke (MELAS) which has an MRI with multifocal infarcts that do not respect vascular territories, potentially with cortical involvement while sparing deeper white matter structures. Another example relates to the MRI finding in cerebral autosomal dominant subcortical infarcts and leukoencephalopathy (CADASIL), which reveals subcortical white matter changes in the extreme capsule, corpus callosum, and the anterior temporal poles’ (O’Sullivan’s sign) [26]. A watershed infarct pattern suggests a more proximal stenosis, potentially indicating atherosclerotic or dissection etiologies.
Heart
Cardioembolic sources of ischemic stroke are the most prevalent [27, 28]. In contrast to older patients whose main source of cardioembolic stroke is atrial fibrillation, the dysrhythmias are less typical offenders in young. Nonetheless, our first line screening tests of the electrical activity of the heart include a standard 12 lead electrocardiogram and telemetry monitoring to screen for dysrhythmias such as atrial fibrillation, atrial flutter, and sick sinus syndrome. Another rationale for the electrocardiograms is to look for evidence of acute myocardial infarction which can lead patients susceptible to developing a left ventricular thrombus and thus a nidus for cardioembolic ischemic stroke.
The next evaluation of the heart is the structural evaluation. Transthoracic echocardiography with bubble study evaluates for a multitude of potential stroke etiologies including left atrial or left ventricular thrombus, cardiac myxomas, infective and nonbacterial endocarditis, rheumatic heart disease, degenerative valvular disease, cardiomyopathy, and patent foramen ovale. Bacterial endocarditis was the most common cardiac cause of stroke in young adults in the Baltimore-Washington Young Stroke [29]. Of these causes, cardiomyopathies are a major risk factor in ischemic strokes in children and young adults with estimates ranging between 10 and 100 times greater relative risk in comparison to control groups even higher than HTN and atrial fibrillation [30,31,32, 33•, 34]. Patent foramen ovale (PFO) is associated with ischemic stroke but management of young adults with ischemic stroke of undetermined etiology and a PFO is controversial; updated guidelines are expected following recent trials [35,36,37]. PFOs are estimated to be prevalent in 25% of the general population and approximately 50% in young stroke patients [11, 15].
There are clinical circumstances where a cardioembolic source is strongly considered, but a source is not identified by the above strategy. In that case, a transesophageal echocardiogram (TEE) is recommended. A recent study showed that TEE lead to changes in management 16.7% of the time with a majority being treatment of PFO but other etiologies discovered included endocarditis, aortic arch atheroma, intracardiac thrombus, pulmonary arteriovenous malformation, and valve masses [38]. Additionally, patients can be evaluated by extended cardiac monitoring both with external and internal devices. Although there are rare familial cases, atrial fibrillation is uncommon in young adults. Data from older patients suggests that through the utilization of implantable loop recorders, atrial fibrillation was detected in 25.5% of patients with stroke of undermined etiology [39••].
Blood vessels of the head and neck
It is imperative to evaluate the vasculature from the aortic arch through the intracerebral vessels in all stroke patients, especially young stroke patients as the second most common cause of stroke in the young is cervicocerebral arterial dissection accounting for 10–25% of ischemic strokes [28, 40,41,42]. The extracranial vertebral arteries are most commonly affected [39••]. A large proportion of dissections is spontaneous but others are associated with minor trauma such as coughing, vomiting, sudden head movement, chiropractic manipulation, and sex. Some studies have concluded that migraine, recent infection, hypertension, smoking, pregnancy, oral conceptive use, hyperhomocysteminemia, and the autumn season are predisposing factors to cervicocephalic dissection [43,44,45,46,47,48,49,50,51,52]. Carotid duplex is of limited value in evaluation of young onset stroke and CTA of head and neck is preferred initial study due to its greater resolution compared to even MRA with contrast. When cerebral venous thrombosis is suspected, delayed images, e.g., CTV, should be obtained.
Another primary reason for imaging the cerebral and neck vasculature is to evaluate for the various arteriopathies that predispose to stroke. Such entities are generally classified into inflammatory versus non-inflammatory arteriopathies. Fibromuscular dysplasia (FMD) describes a group of non-inflammatory arteriopathies that commonly affects young females causing stroke and refractory hypertension and typically affects the renal and cerebral vessels [53,54,55]. Angiography demonstrates the pathognomonic “string-of-beads” pattern. Another classic non-inflammatory arteriopathy that is an established cause of stroke in young (and children) is moyamoya disease, being the cause of 6–15% of nonatherosclerotic vasculopathies [11]. Conventional angiography illustrates the well-known “puff of smoke” appearance resulting from bilateral intracranial carotid artery stenosis/occlusion with associated dilatation of lenticulostriate arteries. The other vasculopathies are listed in Table 1 with associated features to aid in identification when non-specific arteriopathies are discovered on angiography.
Large artery atherosclerosis is one of the more common etiologies in older adults that still must be considered in stroke in young, especially those in their late 30s and 40s with vascular risk factors like diabetes and smoking because large artery atherosclerosis increases after age 35–40 [15,16,17]. This will be less than 10% of the etiologies in stroke in young [11]. This is an important clinical consideration since the 17-year mortality rate in a recent study was 60% when LAA was determined the etiology of stroke in young [74•].
Other considerations
Concurrent with the “heart to head” evaluation, risk stratification labs are checked which include a lipid panel, HgbA1c, Utox, and TSH (if there is a clinical suspicion for atrial fibrillation) along with the standard CBC and CMP. In stroke care, it is imperative to identify the vascular risk factors in order to most appropriately prescribe a therapeutic regimen for secondary prevention. The “heart to head” method employs tactics to identify major risks of recurrence such as large artery atherosclerosis and heart failure; however, diabetes and heavy traditional risk factors are also independent risk factors of recurrent stroke or myocardial infarction [18]. More commonly encountered vascular risk factors in young are hyperlipidemia (60%), smoking (44%), and hypertension (39%) [16, 75]. Although less common, diabetes is a strong risk factor for stroke in patients younger than 55 years old [76]. In addition to the urine toxicology testing, it is imperative to take a thorough history related to alcohol consumption and recreational drug use. Drug use has been implicated in up to 12% of stroke in young [77] and overuse of alcohol has been identified as an independent risk factor for ischemic stroke in the young [78].
Gender is another factor to consider in stroke in young, with certain stroke etiologies more often associated with young women. There is an increased incidence of stroke in women younger than 30 years old compared to men which may be partially attributable to oral contraceptive use, migraine, pregnancy, and puerperium [79]. Stroke risk in female migraineurs with aura has been shown to be doubled in comparison to those without migraines, with further risk increasing in the presence of OCPs and smoking [80,81,82,83]. The triad of migraines, smoking, and OCP must be avoided, as such smoking cessation and discontinuation of OCPs must occur. Pregnancy is a rare cause of stroke but there is an increased risk in the days before birth and up to 6 weeks postpartum with a new study suggesting the increased risk may be up to 12 weeks postpartum [84]. There are other factors including venous infarcts, eclampsia, and reversible cerebral vasoconstriction syndrome (RCVS) playing a role and modulating stroke risk [85, 86].
Hypercoagulable states are an uncommon cause of stroke in young adults and, for most abnormal laboratory findings, evidence is lacking that management should be altered. One notable exception is antiphospholipid antibody syndrome, with an incidence of five cases per 100,000 persons per year [11, 87]. Antiphospholipid antibody syndrome is associated with increased risk of ischemic stroke and recurrence in young adults [88]. In general, screening for hypercoagulable states in first time ischemic stroke in the young is not recommended. Inherited thrombophilias including factor V Leiden mutation, prothrombin gene mutation, protein C deficiency, protein S deficiency, and antithrombin deficiency are associated with earlier venous thrombosis but there is no clear link with ischemic stroke [89]. However, there is some evidence that these hematological factors may be associated early onset stroke risk in the setting of multiple vascular risk factors [90].
Certain clinical examination findings may suggest genetic disorders associated with ischemic stroke. Table 2 lists many of the established monogenic disorders associated with stroke, including young onset stroke. The table framework highlights many of the key-associated clinical manifestations that infer on the diagnosis. Other young onset stroke etiologies that should be considered include collagen vascular diseases, red cell disorders like sickle cell disease (SCD), platelet disorders, and atypical emboli (fat, tumor, and air cholesterol) in the setting of recent trauma or surgery.
Brief discussion of hemorrhagic strokes
Hemorrhagic stroke is a significant cause of mortality and morbidity among stroke in young patients. The incidence in patients under 45 has been estimated to be 3–6 per 100,000 per year for subarachnoid hemorrhage and 2–7 per 100,000 per year in intracerebral hemorrhage (ICH) [91, 92]. Subarachnoid hemorrhage is associated with aneurysm rupture in the overwhelming majority of cases, with arteriovenous malformations and cavernomas being less common. ICH is estimated to be 10–20% of non-traumatic strokes [93]. Lobar hemorrhage represents the majority of the intracerebral hemorrhages, many of which are hypertensive in etiology even among younger patients. Arteriovenous malformations, cavernomas, drug abuse, and bleeding disorders are other etiologies for ICH. ICH has higher mortality in its early stages and a higher morbidity in comparison to ischemic stroke. ICH mortality in the young is 6.1, 10.3, and 13.7% at 5, 10 and 20 years follow-up respectively and is independently associated with male sex and diabetes [93,94,95,96,97]. Although these young patients fared better than elderly counterparts in these studies, their morbidity was pronounced, with less than half of patients having employment 1 year following stroke [93, 95].
Treatment
Hyperacute therapy
Young adult patients with an ischemic stroke are recommended to be treated with intravenous alteplase (IV tPA) when they do not have any contraindications. The treatment window is 0–3 h within symptom onset per the standard-of-care and up to 4.5 h in certain situations as per AHA guidelines. The benefit from tPA is time dependent so it should be given as quickly as possible with goals traditionally being door to needle time < 60 min which will soon be addended to < 45 min [2••]. IV tPA dosage is weight based @ 0.9 mg/kg (maximum 90 mg) with 10% being bolused over the first minute and the remainder being infused over the next 59 min. AHA/ASA guidelines also recommend IV tPA be given to patients who have stroke symptoms 3 to 4.5 h from stroke onset with additional exclusion criteria in this time range including the following: patients > 80 years old, taking any oral anticoagulation regardless of INR, baseline NIHSS > 25, ischemia in more than one third of the MCA territory, and a history of both previous stroke and diabetes mellitus [2••]. The trials that support the use of IV tPA in this extended window are NINDS1&2, ECASS, ECASS2, ECASS3, ATLANTIS, and ATLANTIS-A [98,99,100,101,102,103]. The most recent data suggest that in the setting of large artery occlusive ischemic stroke, there is benefit of clot retrieval interventional therapies in addition to IV tPA. The recent clinical trials supporting this recommendation include MR CLEAN, ESCAPE, EXTEND-IA, SWIFT-PRIME, REVASCAT, and THRACE [104,105,106, 107••, 108••, 109••].
Secondary prevention
Secondary prevention focuses on stopping recurrent strokes. Even young stroke patients demonstrate a significant increase in stroke recurrence (9.4% risk at 5 years) which was attributed to modifiable risk factors [110]. The independent risk factors associated with a 5-year stroke recurrence include diabetes, heart failure, prior transient ischemic attack, large artery atherosclerosis stroke etiology, and traditional risk factors [18]. The highest recurrence risk occurs in the first year after stroke. Hence, it is important to educate patients and their families during the initial hospitalization as well as during subsequent clinic visits regarding the importance of medication compliance and behavioral compliance regarding smoking cessation, a healthy diet, and regular exercise, these among others [18].
Antithrombic therapy
Aspirin is the main therapy for secondary prevention in ischemic strokes not caused by atrial fibrillation [111, 112]. There is some data to suggest a benefit of dual-antiplatelet therapy in the setting of intracranial atherosclerosis following TIA or minor ischemic stroke for 21 and 90 days, as based on the CHANCE and SAMMPRIS studies, respectively [113, 114].
Anticoagulant therapy
Anticoagulation is indicated in the treatment of ischemic stroke due to atrial fibrillation. The recurrence rate of cardioembolic stroke due to atrial fibrillation has been shown to be approximately 8% within 1 week [115]. Studies comparing warfarin to aspirin have consistently demonstrated warfarin superiority for preventing ischemic stroke in atrial fibrillation [116]. Other novel oral anticoagulants have also been studied for prevention of ischemic stroke. Positive studies include ROCKET-AF, ARISTOTLE, and RE-LY [117, 118•, 119]. ROCKET-AF demonstrated that rivaroxaban dosed at 20 mg was not inferior to warfarin and conferred less bleeding risk except gastrointestinal bleeds [117]. ARISTOTLE evaluated apixaban dosed at 5 mg twice a day and showed superiority to warfarin in stroke prevention with secondary outcomes demonstrating less ICH, major bleeding, and death [118•]. Dabigatran 150 mg twice a day was shown to be superior to warfarin in terms of stroke prevention and ICH risk but there was a significant risk for gastrointestinal bleed [119].
One unique consideration in stroke in young patients is empiric anticoagulation therapy. There is no robust data to guide this therapeutic consideration from a purely evidence-based perspective. However, one can consider using empiric anticoagulation in young patients with recurrent ischemic stroke of undetermined etiology. Although in young stroke patients age by definition would be scored zero, the CHA2DS2-VASc risk score can and should be utilized to help infer on anticoagulation use (https://www.mdcalc.com/cha2ds2-vasc-score-atrial-fibrillation-stroke-risk). The ongoing Embolic Stroke of Unknown Source (ESUS) trial will help guide future treatment considerations [120].
Modification of vascular risk factors
Statin therapy
Statin therapy remains a mainstay in for secondary stroke prevention. This is especially true in patients with atherosclerotic risk factors as supported by the SPARCL trial [121]. Although in young stroke patients with non-atherosclerotic risk factors, this remains a topic of debate; however, statins were associated with less recurrent vascular events in young patients with stroke of undetermined etiology [122].
Blood pressure management
The AHA recommends long-term blood pressure management goals of < 140/90 mmHg in non-diabetic patients and < 130/90 mmHg in diabetic patients.
Diet and exercise
In all patients who have experienced a stroke, optimal diet and exercise habits are recommended. Patients should participate in 30 min of moderate exercise at least 3 days a week. We recommend the DASH and Mediterranean diets [123, 124]. For those with diabetes, diabetic diets with low glycemic index are recommended.
Smoking cessation
Patients are counseled during the acute stroke hospitalization, as well as at all subsequent clinical encounters, about the importance of smoking cessation for prevention of subsequent stroke. This is especially important in young stroke patients whose strokes (both ischemic and hemorrhagic) are associated with cigarette smoking [125, 126]. Regarding e-cigarettes, the short-term and long-term health effects are not well established at this time and are an area of intense research.
Diabetes management
Although diabetes is less prevalent in the young as compared to the elderly, screening for diabetes in young stroke patients should be performed. Those who do have diabetes have an estimated 2- to 6-fold increase in stroke risk emphasizing the importance of optimal glucose control [11]. NOMAS investigators found that the risk of ischemic stroke increased 3% annually and tripled in patients with diabetes more than 10 years. Therefore, such patients are referred for diabetes education and follow up with either a primary care physician or endocrinologist depending on diabetic severity.
Surgical procedures
Surgical procedures are reserved for patients with symptomatic carotid stenosis. This is defined as patients with an ischemic stroke in the distribution of an atherosclerotic internal carotid artery. Carotid endarterectomy (CEA) and/or carotid artery stenting (CAS) is recommended in patients (< 70 years old) with TIA or ischemic stroke in the setting of severe ipsilateral carotid artery stenosis defined as 70–99%, this when perioperative morbidity and mortality is 6% or less [127, 128]. Patient specific factors including age, gender, and medical comorbidities should be considered for CEA/CAS with symptomatic carotid stenosis in the 50–69% range [127, 128].
Rehabilitation
Early and intensive multidisciplinary rehabilitation is employed in all stroke patients who are physically able. Physical and occupational therapists begin the rehabilitation assessment and planning process during the acute stroke hospitalization. Following medical workup completion, patients are frequently transferred to an acute rehabilitation facility where physical, occupational, and speech therapists aim to improve the patient’s functional recovery of motor, cognitive, speech, and task-related skills.
Special and pediatric treatment considerations
Sickle cell disease (SCD) is one stroke etiology that employs a disease-specific treatment regime. The landmark STOP trial demonstrated that children (2–16 years old) with elevated transcranial doppler velocities ≥ 200 cm/s should be treated with exchange transfusions for primary stroke prevention [129]. Unfortunately, in older adolescents and young adults with SCD, such clear guidelines do not exist. Typically, patients are not screened beyond the age of 16 years given the absence of data supporting the utility of TCD screening above age 16 years and the changing patterns of cerebral blood flow velocities above this age. This strategy is consistent with recommendations from several groups including the 2014 SCD guidelines from the National Heart, Lung, and Blood Institute [130] and a 2004 publication from the American Academy of Neurology [131]. Lastly, patients with Fabry disease are treated with recombinant alpha galactosidase-A replacement therapy to reduce disease-related complications, but its efficacy in stroke reduction is unclear [132].
References and Recommended Reading
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
Ovbiagele B. Nationwide trends in in-hospital mortality among patients with stroke. Stroke. 2010;41(8):1748–54.
•• Jauch EC, Saver JL, Adams HP, Bruno A, Connors JJB, Demaerschalk BM, et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2013;44(3):870–947. This is the most recent evidence-based guidelines that describes the consensus recommendations for many of the commonly encountered situations related to stroke care. It is an excellent resource to have in clinical practice
• Ramirez L, Kim-Tenser MA, Sanossian N, Cen S, Wen G, He S, et al. Trends in acute ischemic stroke hospitalizations in the United States. J Am Heart Assoc. 2016;5(5):e003233. This is a recent study that highlights the recent trends in stroke hospitalizations namely that stroke in young is increasing in the USA
Lee LK, Bateman BT, Wang S, Schumacher HC, Pile-Spellman J, Saposnik G. Trends in the hospitalization of ischemic stroke in the United States, 1998–2007. Int J Stroke. 2012;7:195–201.
Pathak EB, Sloan MA. Recent racial/ethnic disparities in stroke hospitalizations and outcomes for young adults in Florida, 2001–2006. Neuroepidemiology. 2009;32:302–11.
Kissela BM, Khoury JC, Alwell K, et al. Age at stroke: temporal trends in stroke incidence in a large, biracial population. Neurology. 2012;79:1781–7.
Ovbiagele B. Nationwide trends in in-hospital mortality among patients with stroke. Stroke. 2010;41:1748–54.
Towfighi A, Ovbiagele B, Saver JL. Therapeutic milestone: stroke declines from the second to the third leading organ- and disease-specific cause of death in the United States. Stroke. 2010;41:499–503.
Towfighi A, Saver JL. Stroke declines from third to fourth leading cause of death in the United States: historical perspective and challenges ahead. Stroke. 2011;42:2351–5.
Ovbiagele B, Markovic D, Towfighi A. Recent age- and gender-specific trends in mortality during stroke hospitalization in the United States. Int J Stroke. 2011;6:379–87.
Smajlović D. Strokes in young adults: epidemiology and prevention. Vasc Health Risk Manag. 2015;11:157–64.
Ellis C. Stroke in young adults. Disabil Health J. 2010;3:222–4.
Wei WW, Heeley EL, Jan S, et al. Variations and determinants of hospital costs for acute stroke in China. PLoS One. 2010;5(9):1–8.
Cipriano LE, Steinberg ML, Gazelle GS, Gonzalez RG. Comparing and predicting the costs and outcomes of patients with major and minor stroke using the Boston acute stroke imaging scale neuroimaging classification system. AJNR Am J Neuroradiol. 2009;30:703–9.
Ferro JM, Massaro AR, Mas J-L. Aetiological diagnosis of ischaemic stroke in young adults. Lancet Neurol. 2010;9(11):1085–96.
Putaala J, Metso AJ, Metso TM, et al. Analysis of 1008 consecutive patients aged 15 to 49 with fi rst-ever ischemic stroke: the Helsinki young stroke registry. Stroke. 2009;40:1195–203.
Cerrato P, Grasso M, Imperiale D, et al. Stroke in young patients: etiopathogenesis and risk factors in diff erent age classes. Cerebrovasc Dis. 2004;18:154–9.
Putaala J, Haapaniemi E, Metso AJ, Metso TM, Artto V, Kaste M, et al. Recurrent ischemic events in young adults after first-ever ischemic stroke. Ann Neurol. 2010;68(5):661–71.
Kappelle LJ, Adams HP Jr, Heffner ML, Torner JC, Gomez F, Biller J. Prognosis of young adults with ischemic stroke. A long-term follow-up study assessing recurrent vascular events and functional outcome in the Iowa registry of stroke in young adults. Stroke. 1994;25:1360–5.
Putaala J, Curtze S, Hiltunen S, Tolppanen H, Kaste M, Tatlisumak T. Causes of death and predictors of 5-year mortality in young adults after first-ever ischemic stroke: the Helsinki young stroke registry. Stroke. 2009;40(8):2698–703.
Marini C, Totaro R, Carolei A. Long-term prognosis of cerebral ischemia in young adults. National Research Council Study Group on Stroke in the Young. Stroke. 1999;30:2320–5.
Waje-Andreassen U, Naess H, Thomassen L, Eide GE, Vedeler CA. Long-term mortality among young ischemic stroke patients in western Norway. Acta Neurol Scand. 2007;116:150–6.
Waje-Andreassen U, Thomassen L, Jusufovic M, Power KN, Eide GE, Vedeler CA, et al. Ischaemic stroke at a young age is a serious event–final results of a population-based long-term follow-up in Western Norway. Eur J Neurol. 2013;20:818–23.
Heikinheimo T, Broman J, Haapaniemi E, Kaste M, Tatlisumak T, Putaala J. Preceding and poststroke infections in young adults with first-ever ischemic stroke: effect on short-term and long-term outcomes. Stroke. 2013;44:3331–7.
Nedeltchev K, der Maur TA, Georgiadis D, Arnold M, Caso V, Mattle HP, et al. Ischaemic stroke in young adults: predictors of outcome and recurrence. J Neurol Neurosurg Psychiatry. 2005;76:191–5.
O’Sullivan M, Jarosz JM, Martin RJ, Deasy N, Powell JF, Markus HS. MRI hyperintensities of the temporal lobe and external capsule in patients with CADASIL. Neurology. 2001;56:628–34.
Bassetti C, Carruzzo A, Sturzenegger M, et al. Recurrence of cervical artery dissection: a prospective study of 81 patients. Stroke. 1804;27:1996.
Ducrocq X, Lacour JC, Debouverie M, et al. Accidents vasculaires cérébraux ischemiques du sujet jeune: Étude prospective de 296 patients ages 16 a 45 ans. Rev Neurol (Paris). 1999;155:575.
Kittner SJ, Stern BJ, Wozniak M, et al. Cerebral infarction in young adults: the Baltimore-Washington Cooperative Young Stroke Study. Neurology. 1998;50(4):890–4.
Mackay MT, Wiznitzer M, Benedict SL, Lee KJ, Deveber GA, Ganesan V. International Pediatric Stroke Study G. Arterial ischemic stroke risk factors: the International Pediatric Stroke Study. Ann Neurol. 2011;69:130–40.
Rodan L, McCrindle BW, Manlhiot C, MacGregor DL, Askalan R, Moharir M, et al. Stroke recurrence in children with congenital heart disease. Ann Neurol. 2012;72:103–11.
Fox CK, Sidney S, Fullerton HJ. Community-based case-control study of childhood stroke risk associated with congenital heart disease. Stroke. 2015;46:336–40.
• Dowling MM, Hynan LS, Lo W, Licht DJ, McClure C, Yager JY, et al. International Paediatric Stroke Study: stroke associated with cardiac disorders. Int J Stroke. 2013;8(suppl A100):39–44. Large study that highlights the overwhelming burden of cardiac disease as the predominant etiology in pediatric stroke
Hoffmann A, Chockalingam P, Balint OH, Dadashev A, Dimopoulos K, Engel R, et al. Cerebrovascular accidents in adult patients with congenital heart disease. Heart. 2010;96:1223–6.
Furlan AJ, Reisman M, Massaro J, Mauri L, Adams H, Albers GW, et al. Closure or medical therapy for cryptogenic stroke with patent foramen ovale. N Engl J Med. 2012;366:991–9.
Carroll JD, Saver JL, Thaler DE, Smalling RW, Berry S, MacDonald LA, et al. Closure of patent foramen ovale versus medical therapy after cryptogenic stroke. N Engl J Med. 2013;368:1092–100.
Meier B, Kalesan B, Mattle HP, Khattab AA, Hildick-Smith D, Dudek D, et al. Percutaneous closure of patent foramen ovale in cryptogenic embolism. N Engl J Med. 2013;368:1083–91.
Khariton Y, House JA, Comer L, Coggins TR, Magalski A, Skolnick DG, et al. Impact of transesophageal echocardiography on management in patients with suspected cardioembolic stroke. Am J Cardiol. 2014;114(12):1912–6.
•• Cotter PE, Martin MPJ, Ring L, Warburton EA, Belham M, Pugh PJ. Incidence of atrial fibrillation detected by implantable loop recorders in unexplained stroke. Neurology. 2013;80(17):1546–50. This is a paper that changed clinical practice in terms of how we evaluate patients with strokes of undetermined etiology. This has also likely played a role in the ESUS trial which is evaluating for the appropriate therapy for stroke of undetermined etiology (evaluating anti-coagulation versus aspirin)
Bogousslavsky J, Pierre P. Ischemic stroke in patients under age 45. Neurol Clin. 1992;10:113.
Gautier JC, Pradat-Diehl P, Loron P, et al. Accidents vasculaires cérébraux des sujets jeunes. Une etude de 133 patients age de 9 a 45 ans. Rev Neurol (Paris). 1989;145:437.
Lisovoski F, Rousseaux P. Cerebral infarction in young people: a study of 148 patients with early cerebral angiography. J Neurol Neurosurg Psychiatry. 1991;54(576):1895119.
Mokri B, Sundt TM, Houser OW, et al. Spontaneous dissection of the cervical internal carotid artery. Ann Neurol. 1986;19(126):3963755.
Schievink WI, Mokri B, Piepgras DG. Fibromuscular dysplasia of the internal carotid artery associated with alpha-1-antitrypsin deficiency. Neurosurgery. 1998;43:229.
D’Anglejean-Chatillon J, Ribeiro V, Mas JL, et al. Migraine—a risk factor for dissection of cervical arteries. Headache. 1989;29(560):2583992.
Fisher CM. The headache and pain of spontaneous carotid dissection. Headache. 1982;22(60):7085262.
Pezzini A, Grassi M, Del Zotto E, et al. Migraine mediates the influence of C677T MTHFR genotypes on ischemic stroke risk with a stroke-subtype effect. Stroke. 2007;38(3145):17962595.
Grau AJ, Brandt T, Forsting M, et al. Infection-associated cervical artery dissection: three cases. Stroke. 1997;28(453):9040705.
Grau AJ, Brandt T, Buggle F, et al. Association of cervical artery dissection with recent infection. Arch Neurol. 1999;56(851):10404987.
Constantinescu CS. Association of varicella-zoster virus with cervical artery dissection in 2 cases [letter]. Arch Neurol. 2000;57(427):10714677.
Wiebers DO, Mokri B. Internal carotid artery dissection after childbirth. Stroke. 1985;16(956):4089927.
Mas J-L, Bousser M-G, Corone P, et al. Dissecting aneurysm of the extracranial vertebral arteries and pregnancy. Rev Neurol (Paris). 1987;143(761):3432849.
Kirton A, Crone M, Benseler S, Mineyko A, Armstrong D, Wade A, et al. Fibromuscular dysplasia and childhood stroke. Brain. 2013;136(6):1846–56.
Slovut DP, Olin JW. Fibromuscular dysplasia. N Engl J Med. 2004;350:1862–71.
Touze E, Oppenheim C, Trystram D, Nokam G, Pasquini M, Alamowitch S, et al. Fibromuscular dysplasia of cervical and intracranial arteries. Int J Stroke. 2010;5:296–305.
Rennebohm RM, Egan RA, Susac JO. Treatment of Susac’s syndrome. Curr Treat Options Neurol. 2008;10:67–74.
Homocystinuria (OMIM: 236200). http://www.omim.org/.
Familial HDL deficiency – type I (OMIM: 205400). http://www.omim.org/.
Kamada F, Aoki Y, Narisawa A, Abe Y, Komatsuzaki S, Kikuchi A, et al. A genome-wide association study identifies RNF213 as the first Moyamoya disease gene. J Hum Genet. 2011;56:34–40.
CADASIL—cerebral autosomol dominant subcortical infarcts and leukoencephaly (OMIM: 125310). http://www.omim.org/.
CARASIL (OMIM: 600142). http://www.omim.org.
Fabry disease (OMIM 301500). http://www.omim.org/.
Brain small vessel disease with hemorrhage—COL4A1 (OMIM 607595). http://www.omim.org.
TREX spectrum disorders (OMIM: 192315). http://www.omim.org/.
Sickle cell disease (OMIM: 603903). http://www.omim.org/.
Protein C deficiency (OMIM: 176860). http://www.omim.org.
Protein S deficiency (OMIM: 176880, 612336). http://www.omim.org/.
Factor V Leiden mutation (OMIM: 227400). http://www.omim.org.
MELAS—Mitochondrial encephalopathy lactic acidosis and stroke (OMIM:540000). http://www.omim.org/.
Ehlers-Danlos syndrome—type IV (OMIM: 130050). http://www.omim.org/.
Marfan syndrome (OMIM: 154700). http://www.omim.org/.
Fibromuscular dysplasia (OMIM: 135580). http://www.omim.org/.
Pseudoxanthoma elasticum—AD form (OMIM: 177850), AR form (OMIM: 264800). http://www.omim.org/.
• Aarnio K, Haapaniemi E, Melkas S, Kaste M, Tatlisumak T, Putaala J. Long-term mortality after first-ever and recurrent stroke in young adults. Stroke. 2014;45(9):2670–6. This study highlights the importance of aggressive prevention of recurrent stroke given the strikingly high mortality rate associated with recurrent strokes in young patients.
Love BB, Biller J, Jones MP, Adams HP Jr, Bruno A. Cigarette smoking. A risk factor for cerebral infarction in young adults. Arch Neurol. 1990;47:693–8.
Kissela BM, Khoury J, Kleindorfer D, et al. Epidemiology of ischemic stroke in patients with diabetes: the Greater Cincinnati/Northern Kentucky Stroke Study. Diabetes Care. 2005;28:355–9.
Sloan MA, Kittner SJ, Feeser BR, et al. Illicit drug-associated ischemic stroke in the Baltimore-Washington Young Stroke Study. Neurology. 1998;50:1688–93.
Sundell L, Salomaa V, Vartiainen E, Poikolainen K, Laatikainen T. Increased stroke risk is related to a binge-drinking habit. Stroke. 2008;39:3179–84.
Rasura M, Spalloni A, Ferrari M, et al. A case series of young stroke in Rome. Eur J Neurol. 2006;13:146–52.
Bousser MG, Welch KM. Relation between migraine and stroke. Lancet Neurol. 2005;4:533–42.
Schurks M, Rist PM, Bigal ME, Buring JE, Lipton RB, Kurth T. Migraine and cardiovascular disease: systematic review and meta-analysis. BMJ. 2009;339:b3914.
Etminan M, Takkouche B, Isorna FC, Samii A. Risk of ischaemic stroke in people with migraine: systematic review and meta-analysis of observational studies. BMJ. 2005;330:63.
Curtis KM, Mohllajee AP, Peterson HB. Use of combined oral contraceptives among women with migraine and nonmigrainous headaches: a systematic review. Contraception. 2006;73:189–94.
Kamel H, Navi BB, Sriram N, Hovsepian DA, Devereux RB, MSV E. Risk of a thrombotic event after the 6-week postpartum period. N Engl J Med. 2014;370:1307–15.
Sharshar T, Lamy C, Mas JL. Incidence and causes of strokes associated with pregnancy and puerperium. A study in public hospitals of Ile de France. Stroke in Pregnancy Study Group. Stroke. 1995;26:930–6.
Helms AK, Kittner SJ. Pregnancy and stroke. CNS Spectr. 2005;10:580–7.
Gómez-Puerta JA, Cervera R. Diagnosis and classification of the antiphospholipid syndrome. J Autoimmun. 2014;48-49:20–5.
Powers WJ (ed). Cerebrovascular diseases: controversies and challenges. Neurol Clin. 2015;33(2):315–540
Morris JG, Sngh S, Fisher M. Testing for inherited rhrombophilias in arterial stroke: can it cause more harm than good? Stroke. 2010;41(12):2985–90.
Hamedani AL, Cole JW, Cheng Y, et al. Factor V Leiden and ischemic stroke risk: the genetics of early onset stroke (GEOS) study. J Stroke Cerebrovasc Dis. 2013;22(4):419–23.
Marini C, Totaro R, De Santis F, Ciancarelli I, Baldassarre M, Carolei A. Stroke in young adults in the community-based L’Aquila registry: incidence and prognosis. Stroke. 2001;32:52–6.
Jacobs BS, Boden-Albala B, Lin IF, Sacco RL. Stroke in the young in the northern Manhattan stroke study. Stroke. 2002;33:2789–93.
Koivunen R-J, Tatlisumak T, Satopää J, Niemelä M, Putaala J. Intracerebral hemorrhage at young age: long-term prognosis. Eur J Neurol. 2015;22(7):1029–37.
Feigin VL, Lawes CM, Bennett DA, Barker-Collo SL, Paraq V. Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic review. Lancet Neurol. 2009;8:355–69.
Koivunen R-J, Satopää J, Meretoja A, et al. Incidence, risk factors, etiology, severity, and short-term outcome of non-traumatic intracerebral hemorrhage in young adults. Eur J Neurol. 2015;22:123–32.
Schepers VP, Ketelaar M, Visser-Meily AJ, de Groot V, Twisk JW, Lindeman E. Functional recovery differs between ischaemic and haemorrhagic stroke patients. J Rehabil Med. 2008;40:487–9.
Kelly PJ, Furie KL, Shafqat S, Rallis N, Chang Y, Stein J. Functional recovery following rehabilitation after hemorrhagic and ischemic stroke. Arch Phys Med Rehabil. 2003;84:968–72.
The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995;333:1581–7.
Hacke W, Kaste M, Fieschi C, et al. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The european cooperative acute stroke study (ECASS). JAMA. 1995;274:1017–25.
Hacke W, Kaste M, Fieschi C, et al. Randomised double-blind Figure 2. Relationship of time from symptom onset to emergency department arrival and time to treatment. From (28): Albers GW, Bates VE, Clark WM, Bell R, Verro P, Hamilton SA. Intravenous tissue-type plasminogen activator for treatment of acute stroke: the standard treatment with alteplase to reverse stroke (STARS) study. JAMA. 2000;283:1145–50. Reprinted with permission, copyright © 2000 American Medical Association. All rights reserved. IV tPA for Stroke 103 placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators. Lancet 1998;352: 1245–51.
Wahlgren N, Ahmed N, Davalos A, et al. Thrombolysis with alteplase 3–4.5 h after acute ischaemic stroke (SITS-ISTR): an observational study. Lancet. 2008;372:1303–9.
Clark WM, Wissman S, Albers GW, Jhamandas JH, Madden KP, Hamilton S. Recombinant tissue-type plasminogen activator (alteplase) for ischemic stroke 3 to 5 hours after symptom onset. The ATLANTIS study: a randomized controlled trial. Alteplase thrombolysis for acute noninterventional therapy in ischemic stroke. JAMA. 1999;282:2019–26.
Clark WM, Albers GW, Madden KP, Hamilton S. The rtPA (alteplase) 0- to 6-hour acute stroke trial, part a (A0276g): results of a double-blind, placebo-controlled, multicenter study. Thromblytic therapy in acute ischemic stroke study investigators. Stroke. 2000;31:811–6.
Berkhemer OA, Fransen PSS, Beumer D, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015;372(1):11Y20. https://doi.org/10.1056/NEJMoa1411587.
Goyal M, Demchuk AM, Menon BK, et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015;372(11):1019Y1030. https://doi.org/10.1056/NEJMoa1414905.
Campbell BC, Mitchell PJ, Kleinig TJ, et al. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015;372(11):1009Y1018. https://doi.org/10.1056/NEJMoa1414792.
•• Saver JL, Goyal M, Bonafe A, et al. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl Med. 2015;372(24):2285Y2295. https://doi.org/10.1056/NEJMoa1415061. One of the studies that was integral in the ground-breaking shift in acute stroke care showing IV tPa plus thrombectomy was optimal for large vessel occlusive strokes
•• Jovin TG, Chamorro A, Cobo E, et al. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med. 2015;372(24):2296Y2306. https://doi.org/10.1056/NEJMoa1503780. One of the studies that was integral in the ground-breaking shift in acute stroke care showing IV tPa plus thrombectomy was optimal for large vessel occlusive strokes
•• Bracard S, Ducrocq X, Mas JL. Mechanical thrombectomy after intravenous alteplase versus alteplase alone after stroke (THRACE): a randomized controlled trial. Lancet Neurol. 2016;15(11):1138Y1147. https://doi.org/10.1016/S1474-4422(16)30177-6. One of the studies that was integral in the ground-breaking shift in acute stroke care showing IV tPa plus thrombectomy was optimal for large vessel occlusive strokes
Homma S, Sacco RL, Di Tullio MR, Sciacca RR, Mohr JP. Effect of medical treatment in stroke patients with patent foramen ovale: patent foramen ovale in cryptogenic stroke study. Circulation. 2002;105(22):2625–31.
Wang YYYY, Zhao X, Liu L, Wang D, Wang CC, Li H, et al. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med. 2013;369(1):11–9.
Chimowitzmarc I, Lynnmichael J, Derdeyn CP, Turan TN, Fiorella D, Lane BF, et al. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl J Med. 2011;365:993–1003.
Homma S, Thompson JLP, Pullicino PM, Levin B, Freudenberger RS, Teerlink JR, et al. Warfarin and aspirin in patients with heart failure and sinus rhythm. N Engl J Med. 2012;366:1859–69.
Chimowitz MI, Lynn MJ, Howlett-Smith H, Stern BJ, Hertzberg VS, Frankel MR, et al. Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis. N Engl J Med. 2005;352(13):1305–16.
Berge E, Abdelnoor M, Nakstad PH, Sandset PM. Low molecular-weight heparin versus aspirin in patients with acute ischaemic stroke and atrial fibrillation: a double-blind randomised study: HAEST Study Group: Heparin in Acute Embolic Stroke Trial. Lancet. 2000;355:1205–10.
Connolly S, Pogue J, Hart R, Pfeffer M, Hohnloser S, Chrolavicius S, et al. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events. Lancet. 2006;367(9526):1903–12.
Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883–91.
• Hart RG, Catanese L, Perera KS, Ntaios G, Connolly SJ. Embolic stroke of undetermined source a systemic review and clinical update. Stroke. 2017;48:867–72. On-going trial that will be helpful in determining the appropriate treatment for patients with stroke of undetermined etiology
Amarenco P, Bogousslavsky J, Callahan A III, Goldstein LB, Hennerici M, Rudolph AE, et al. Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006;355:549–59.
Putaala J, Haapaniemi E, Kaste M, Tatlisumak T. Statins after ischemic stroke of undetermined etiology in young adults. Neurology. 2011;77:426–30.
SPRINT Research Group, Wright JT Jr, Williamson JD, Whelton PK, Snyder JK, Sink KM, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373(22):2103–16.
Gaciong Z, Siński M, Lewandowski J. Blood pressure control and primary prevention of stroke: summary of the recent clinical trial data and meta-analyses. Curr Hypertens Rep. 2013;15:559–74.
He FJ, Nowson CA, MacGregor GA. Fruit and vegetable consumption and stroke: metaanalysis of cohort studies. Lancet. 2006;367:320–6.
Li XY, Cai XL, Bian PD, Hu LR. High salt intake and stroke: meta-analysis of the epidemiologic evidence. CNS Neurosci Ther. 2012;18:691–701.
Shinton R, Beevers G. Meta-analysis of relation between cigarette smoking and stroke. BMJ. 1989;298:789–94.
Feigin V, Parag V, Lawes CM, et al. Asia Pacific Cohort Studies Collaboration. Smoking and elevated blood pressure are the most important risk factors for subarachnoid hemorrhage in the Asia-Pacific region: an overview of 26 cohorts involving 306,620 participants. Stroke. 2005;36:1360–5.
Meschia JF, Bushnell C, Boden-Albala B, Braun LT, Bravata DM, Chaturvedi S, et al. Guidelines for the primary prevention of stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45:3754–832.
Kernan WN, Ovbiagele B, Black HR, Bravata DM, Chimowitz MI, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45(7):2160–236. https://doi.org/10.1161/STR.0000000000000024.
Adams RJ, McKie VC, Brambilla D, Carl E, Gallagher D, Nichols FT, et al. Stroke prevention trial in sickle cell anemia. Control Clin Trials. 1998;19(1):110–29.
Yawn BP, Buchanan GR, Afenyi-Annan AN, et al. Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members. JAMA. 2014;312:1033.
Sloan MA, Alexandrov AV, Tegeler CH, et al. Assessment: transcranial Doppler ultrasonography: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2004;62:1468.
Wozniak MA, Kittner SJ, Tuhrim S, Cole JW, Stern B, Dobbins M, et al. Frequency of unrecognized Fabry disease among young European-American and African-American men with first ischemic stroke. Stroke. 2010;41(1):78–81.
Acknowledgements
This work was supported, in part, by the Department of Veterans Affairs, Baltimore, Office of Research and Development, Medical Research Service; the Department of Veterans Affairs Stroke Research Enhancement Award Program; National Institute of Neurological Disorders and Stroke (NINDS), and; the American Heart Association. The funders had no role in preparation of the article.
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Stack, C.A., Cole, J.W. A Diagnostic Approach to Stroke in Young Adults. Curr Treat Options Cardio Med 19, 84 (2017). https://doi.org/10.1007/s11936-017-0587-6
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DOI: https://doi.org/10.1007/s11936-017-0587-6