Stroke in young adults under 45 years, while infrequent, has significant societal and personal impacts, with an incidence rate of about 6/100,000. Key pathogenic factors include atherosclerosis in men over 35 and conditions like cardiac diseases and migraine in women under 35. The prognosis for young stroke patients is generally favorable, though long-term outcomes can depend on various risk factors and underlying conditions.

1. Stroke in Young

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Available online at www.sciencedirect.com
ScienceDirect
journal homepage: www.elsevier.com/locate/apme
Review Article
Stroke in young
Pushpendra Nath Renjen*
Sr. Consultant Neurologist & Academic Coordinator, Institute of Neurosciences, Indraprastha Apollo Hospitals,
New Delhi 110076, India
article info
abstract
Article history:
Stroke in people under 45 years of age is less frequent than in older populations but has a
Received 8 August 2013
major impact on the individual and society. In this article we provide an overview of the
Accepted 17 October 2013
epidemiology and etiology of young stroke.
Available online 20 November 2013
Cerebral ischemia in young adults occurs at an annual incidence rate of about 6/100,000.
Although it represents only about 1% of all strokes, it has a relevant impact on years of
Keywords:
potential life lost and on socioeconomic costs, considering the long life expectancy at these
Cerebral ischemia
ages. There is general agreement on the role of atherosclerosis in men over age 35 and of
Prognosis
cardiac diseases, migraine, and oral contraceptive use in women under age 35 as patho-
Young adult
genic determinants for cerebral ischemia. Whether the early onset of stroke in young
Stroke
adults might reflect severity of underlying pathology is still an open question. The shortterm prognosis of stroke in young adults is considered favorable, despite its relationship
with the presence and severity of complications at the time of the first event. Long-term
prognosis of young patients with transient ischemic attack is reported to be even more
favorable, although the risk of new ischemic events depends on the presence of vascular
risk factors. The available prospective studies report annual incidence rates of death and
recurrent stroke ranging from 1% to 2.6%, with higher long-term mortality in patients who
had large-vessel stroke. The prognosis has been reported to be severe in patients with
carotid stenosis and mild in patients with coexisting stroke and migraine.
Copyright ª 2013, Indraprastha Medical Corporation Ltd. All rights reserved.
1.
Introduction
Stroke in people under 45 years of age is less frequent than in
older populations but has a major impact on the individual
and society. In this article we provide an overview of the
epidemiology and etiology of young stroke.
Cerebral ischemia in young adults occurs at an annual
incidence rate of about 6/100,000. Although it represents only
about 1% of all strokes, it has a relevant impact on years of
potential life lost and on socioeconomic costs, considering the
long life expectancy at these ages.1 There is general
agreement on the role of atherosclerosis in men over age 35
and of cardiac diseases, migraine, and oral contraceptive use
in women under age 35 as pathogenic determinants for cerebral ischemia.2,3 Whether the early onset of stroke in young
adults might reflect severity of underlying pathology is still an
open question.3
The short-term prognosis of stroke in young adults is
considered favorable, despite its relationship with the presence and severity of complications at the time of the first
event.4,5 Long-term prognosis of young patients with transient
ischemic attack (TIA) is reported to be even more favorable,
* Tel.: þ91 11 29871016, þ91 9810059614 (mobile).
E-mail address: pnrenjen@hotmail.com.
0976-0016/$ e see front matter Copyright ª 2013, Indraprastha Medical Corporation Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.apme.2013.10.008

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although the risk of new ischemic events depends on the
presence of vascular risk factors.6,7 The available prospective
studies report annual incidence rates of death and recurrent
stroke ranging from 1% to 2.6%, with higher long-term mortality in patients who had a large-vessel stroke.5,8,9 The
prognosis has been reported to be severe in patients with carotid stenosis and mild in patients with coexisting stroke and
migraine.10
2.
Etiologies
The range of potential etiologies for stroke in young adults is
broader than that for older adults (Table 1). Like in older
adults, stroke in younger adults is typically categorized as
primarily ischemic or hemorrhagic. Ischemic etiologies
include cardioembolic, atherosclerotic disease, and nonatherosclerotic cerebral vasculopathies. Hemorrhagic strokes
include subarachnoid and intraparenchymal types. Of
particular note in young adults are stroke causes such as hematologic disorders, substance abuse, trauma, dissections,
oral contraceptive use, pregnancy and postpartum states, and
migraine.
3.
Clinical manifestations
The clinical presentations for stroke in young adults are not
unique to this age group. Sudden or subacute onset of
neurologic symptoms referable to the brain should suggest
stroke as a potential explanation. The presence of a given
stroke risk factor does not assure that it is causative. Many
young patients have multiple risk factors. Detailed history and
examination, oriented toward common and uncommon etiologies, are especially important. Stroke mimics in the young
adult population include multiple sclerosis and malignancy.
The physical exam should include neurologic, cardiovascular, ophthalmologic and dermatologic assessments. Relevant
ocular
findings
include
corneal
arcus
(hypercholesterolemia) or corneal opacity (Fabry’s disease);
Lisch nodules, optic atrophy (neurofibromatosis); lens subluxation (Marfan’s syndrome, homocystinuria); and retinal
perivasculitis (sickle-cell disease, syphilis, connective tissue
diseases, inflammatory bowel disease), occlusions (emboli),
angioma (cavernous malformation), or hamartoma (tuberous
sclerosis). Among dermatologic associations are splinter
hemorrhages or needle tracks (endocarditis); xanthoma
Table 1 e Differential diagnosis of stroke in young adults.
Ischemic
Cardiac disease (including congenital, rheumatic valve disease, mitral valve prolapse, patent foramen ovale, endocarditis, atrial myxoma,
arrhythmias, cardiac surgery)
Large vessel disease
Premature atherosclerosis.
Dissection (spontaneous or traumatic).
Inherited metabolic diseases (homocystinuria, Fabry’s, pseudoxanthoma elasticum, MELAS syndrome).
Fibromuscular dysplasia.
Infection (bacterial, fungal, tuberculosis, syphilis, Lyme).
Vasculitis (collagen vascular diseases e systemic lupus erythematosus, rheumatoid arthritis, Sjogren’s syndrome, polyarteritis nodosa;
¨
Takayasu’s disease, Wegener’s syndrome, cryoglobulinemia, sarcoidosis, inflammatory bowel disease, isolated central nervous system
angiitis).
Moyamoya disease.
Radiation.
Toxic (illicit drugs e cocaine, heroin, phencyclidine; therapeutic drugs e l-asparaginase, cytosine arabinoside).
Small vessel disease
Vasculopathy (infectious, noninfectious, microangiopathy).
Hematologic disease
Sickle-cell disease.
Leukemia.
Hypercoagulable states (antiphospholipid antibody syndromes, deficiency of antithrombin III or protein S or C, resistance to activated
protein C, increased factor VIII).
Disseminated intravascular coagulation.
Thrombocytosis.
Polycythemia vera.
Thrombotic thrombocytopenic purpura.
Venous occlusion (dehydration, parameningeal infection, meningitis, neoplasm, polycythemia, leukemia, inflammatory bowel disease).
Migraine
Hemorrhagic
Subarachnoid hemorrhage (cerebral aneurysm)
Intraparenchymal hemorrhage
Arteriovenous malformation.
Neoplasm (primary central nervous system, metastatic, leukemia).
Hematologic (sickle-cell disease, neoplasm, thrombocytopenia), moyamoya disease.
Drug use (warfarin, amphetamines, cocaine, phenylpropanolamine).
Iatrogenic (peri-procedural).

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´
(hyperlipidemia); cafe-au-lait spots, neurofibromas (neurofibromatosis); purpura (coagulopathy); and capillary angioma
(cavernous malformation).11
One-fifth to one-third of strokes in the young may be
caused by cardioembolic phenomena. Transesophageal
echocardiography (TEE) is usually indicated. Causes include
congenital heart disease, valvular disease (including endocarditis) and arrhythmias. Mitral valve prolapse and patent
foramen ovale are common but are typically not causes of
stroke when present. An atrial septal aneurysm is less likely to
be associated with stroke when found in isolation than when
it occurs with other cardiac abnormalities.
Premature atherosclerotic cerebrovascular disease can be
symptomatic in young adults, just as atherosclerosis can
begin in childhood. The symptoms and signs are similar to
those for older adults.
Cervicocephalic arterial dissections can involve the extracranial internal carotid, the vertebrobasilar system, or, less
commonly, the intracranial carotid system. They are associated with major or minimal trauma, chiropractic manipulation,
or can occur spontaneously. Other associations include fibromuscular dysplasia, Marfan syndrome, EhlerseDanlos syndrome type IV, moyamoya and sympathomimetic drug abuse.
Symptoms and signs may include neck pain, transient or lasting ischemia of retina, cerebral hemispheres, or posterior fossa,
Horner’s syndrome, hemicranial pain, or subarachnoid hemorrhage. Extracranial ultrasound or magnetic resonance angiography (MRA) may confirm the clinical impression. Often
catheter angiography is required for diagnosis.
Cerebral vasculitis should be considered for cases of
ischemic or hemorrhagic stroke, recurrent strokes, stroke
with encephalopathy, and stroke with fever, multifocal
symptoms, skin abnormalities, or abnormal renal function or
sedimentation rate. Infectious vasculitis (eg, with syphilis,
tuberculosis, purulent meningitis), necrotizing vasculitis (eg,
polyarteritis nodosa), vasculitis with collagen vascular disease
(eg, lupus, rheumatoid arthritis), giant cell arteritis, and hypersensitivity vasculitis (eg, drug-induced) are seen much
more often than primary central nervous system vasculitis.
Moyamoya is a noninflammatory vasculopathy associated
with extensive collateral vasculature. It can present with
transient ischemic attacks, headaches, hemiparesis, seizures,
cerebral infarction, or hemorrhage. MRA screening is useful.
Angiographic findings are distinctive and resemble in part a
“puff of smoke”.12
Hypercoagulable states may be responsible for 2%e7% of
cases in young adults. Inherited (primary) thrombophilic disorders include entities that are recently described (hyperhomocysteinemia, factor V Leiden, prothrombin G20210A),
well-established (deficiencies of antithrombin, protein S or
protein C), and extremely rare (dysfibrinogenemia, thrombomodulin deficiency, heparin cofactor II deficiency).13 Acquired
(secondary) causes include malignancy, pregnancy/postpartum states, oral contraceptive use and sickle-cell disease.
Prior thromboembolic disease in a young patient or in family
members should raise suspicion.12
Cerebral venous thrombosis can cause ischemic or hemorrhagic strokes. Septic thrombosis usually occurs at the
cavernous sinus as a complication of facial infection. Signs
include proptosis, chemosis, and gaze palsies. Aseptic
267
thromboses are seen disproportionately in women during
pregnancy or postpartum periods, or while taking oral contraceptives. Presenting symptoms include headache, emesis,
lethargy, and seizures. Papilledema may accompany focal
signs.12,14
Strokes induced by migraines are rare, considering that
perhaps 20% of US adults may suffer migraines. Symptoms
include persistent visual, motor, sensory or aphasic deficits,
which began in the course of a typical migraine attack, where
other causes are excluded. Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS)
syndrome and cerebral autosomal dominant arteriopathy
with subcortical infarcts and leukoencephalopathy (CADASIL)
are inherited causes of stroke which can include migraine as
part of the clinical presentation.11,12
Up to 45% of strokes in young adults are due to spontaneous intracerebral hemorrhage.12 Approximately half are
lobar; one-quarter are in basal ganglia or internal capsule.15
Vascular malformations, aneurysms, hypertension, and
illicit drug use are the main causes.12,15
4.
Investigations
The initial work-up should be as expeditious as possible to
allow consideration of acute therapies, such as tissue plasminogen activator (t-PA).16 Brain computed tomography (CT)
is usually the initial imaging study of choice as it is readily
available and is highly sensitive for acute hemorrhage. Blood
work should include a complete blood count with differential
and platelet count, prothrombin time (international normalized ratio), activated partial thromboplastin time, glucose,
chemistries, electrolytes, serology for syphilis, and an erythrocyte sedimentation rate.
A more detailed coagulation profile (anticardiolipin antibodies, lupus anticoagulants, protein S, protein C, activated
protein C resistance, antithrombin III) is requested in patients
without a firmly identified cause of stroke or if the patient or
family members have a history of thromboses. It is advantageous to send such a profile prior to initiating anticoagulation,
as heparin can alter interpretation of some of those assays.
Therefore, consider ordering these assays at the beginning of
the work-up.
Most patients should have high-quality brain magnetic
resonance imaging (MRI) and often MRA.12,17 Where available,
MRI with diffusion-weighted imaging (DWI) and perfusion
imaging (PI) is becoming standard. DWI-PI has the potential to
distinguish irreversibly injured tissue from that which may be
salvageable.18
Additional studies in initial screening include pregnancy
testing, a chest roentgenogram, and an electrocardiogram. An
echocardiogram (consider transesophageal), and extracranial
(carotid-vertebral) Doppler ultrasound are routinely obtained,
although often after initial antiplatelet or anticoagulation
therapy is started.
Keep in mind the limitations of studies performed. CT will
miss a minority of acute bleeds. MRI with DWI, quite sensitive
for acute stroke, has an occasional false negative result (17 out
of 782 patients in a recent study).19 Also, MRA’s resolution is
not yet on par with conventional angiography.

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Consider conventional angiography of cerebral and neck
vessels for patients in whom dissection is suspected or in
whom no other cause is found. Transcranial Doppler ultrasound can be helpful.
Toxicologic studies are often productive, even when drug
use is not acknowledged.
Other blood tests may include homocysteine, fibrinogen,
antinuclear antibody, lipid panel, lipoprotein (a), serum protein electrophoresis, hemoglobin electrophoresis, and sicklecell assay. Cerebrospinal fluid analysis is indicated for cases
suspicious for infectious, vasculitic, or occult hemorrhage
origins. Telemetry monitoring for arrhythmias is occasionally
revealing.12
Prothrombin mutation G20210A testing is of uncertain
utility in cerebrovascular disease, but may be appropriate for
patients with a personal history of thromboembolic disease or
family history of thrombophilia.
A patient with one or more risk factors, such as migraine or
diabetes, should be thoroughly investigated for other possibilities. The cause of stroke in young patients may remain
undetermined in 20%e30% of cases, even after a detailed
work-up.12
5.
and intracranial vessels. Whilst the commonest cause of
cardioembolic stroke in the elderly is atrial fibrillation, in a
young patient transesophageal echocardiography looking for
the presence of a patent foramen ovale Æ an atrial septal
aneurysm will have a higher yield. One must not forget,
however, that atherosclerosis still contributes to a large proportion of stroke in young patients and likely explains at least
some of the ethnic differences noted in the incidence of
stroke, emphasizing the need for aggressive risk factor management. This, as well as differences in the prevalence of
other causative etiologies, such as rheumatic fever and
infection, combined with a younger background population
age distribution, may contribute to an increased incidence of
young stroke in developing countries. Finally, the incidence of
stroke appears greater in women than men under the age of
30, and women are at increased risk of hemorrhage and
infarction in the puerperium. Additional history, including
use of the oral contraceptive pill, and testing for antiphospholipid antibodies is important in young women. There
is a need for further research in young stroke, particularly
population-based studies utilizing standardized methodology.
These will provide clarity by enabling comparison of incidence
rates between countries and trends overtime, and insights
into underlying etiological mechanisms.
Management
General management of ischemic and hemorrhagic strokes is
similar to that for older adults and is beyond the scope of this
article. Additional specific measures are oriented toward any
underlying etiology found.
Conflicts of interest
The author has none to declare.
references
6.
Prognosis
The outcome of stroke in young adults is better than that for
older adults. In a recent study of 330 patients with first stroke
or transient ischemic attack, followed for an average of 96
months, 8% died, 3% had another stroke, and 3% had a
myocardial infarction. Approximately 16% were dependent,
but 56% had returned to work. Unfortunately, only a minority
of those who smoked at the time of their stroke subsequently
stopped using tobacco. The overall annual recurrence rate is
less than 1%. Prognosis is often closely associated with the
underlying cause. A relatively good outcome may be found
after many cases of arterial dissection. Risk of stroke recurrence is low (2% over 5 years) in women whose first stroke
occurred in pregnancy.
7.
Conclusion
In summary, stroke in the young requires a different approach
to investigation and management than stroke in the elderly
given differences in the relative frequencies of possible underlying causes. Haemorrhagic stroke is common, and
vascular imaging is recommended given a high frequency of
underlying vascular anomalies. It is also important to explore
the possibility of illicit drug use in these cases. With regard to
ischemic stroke, the increased frequency of dissection mandates a high index of suspicion for imaging the extracranial
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