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Stroke in Young AdultsHeather Bevan, MD, Khema Sharma, MD, and Walter Bradley, DM, FRCP

Strokes in young adults are uncommon and often a diagnostic challenge. A retrospective study ofstrokes due to intracerebral hemorrhage, subarachnoid hemorrhage, or cerebral infarction wasundertaken. We reviewed the medical records of 113 young patients aged 15-45 years who wereadmitted to the Medical Center Hospital of Vermont with a diagnosis of stroke between 1982 and1987. This group comprised 8.5% of patients of all ages admitted for stroke, 23 times theproportion observed in the National Survey of Stroke. Nontraumatic intracerebral hemorrhagewas diagnosed in 46 young patients (41%); the main causes included aneurysms, arteriovenousmalformations, hypertension, and tumors. Subarachnoid hemorrhage was found in 19 youngpatients (17%); the majority were due to aneurysms. The remaining 48 young patients (42%) hadcerebral infarction, the majority due to cardiogenic emboli and premature atherosclerosis. Mitralvalve prolapse, the use of oral contraceptives, alcohol drinking, and migraine were infrequent solecauses of cerebral infarction in the absence of other risk factors. The case-fatality rate for thisgroup of young patients with stroke was 20.4% compared with 23.9% for the National Survey ofStroke. Young adults with stroke deserve an extensive but tailored evaluation, which shouldinclude angiography and echocardiography. (Stroke 1990^1:382-386)

Strokes in young adults are relatively uncommon;the disorder usually occurs in the middle-agedand elderly. The National Survey of Stroke

revealed that only 3.7% of all strokes occurred inpatients aged 15-45 years.1 The etiologic and prog-nostic features that characterize strokes in older per-sons may not apply to young adults. Previous reportssuggest that a cause can be found in 55-93% of youngpeople with stroke,2-4 but there is considerable varia-tion in causes among studies; therefore, further stud-ies are needed. We have reviewed our experience in aregional referral hospital.

Subjects and MethodsWe retrospectively reviewed the medical records of

all patients aged 15-45 years with the diagnosis ofhemorrhagic or nonhemorrhagic stroke admitted tothe Medical Center Hospital of Vermont betweenJanuary 1,1982 and December 31,1987. We includedpatients who suffered subarachnoid hemorrhage(SAH), intracerebral hemorrhage (ICH), or cerebralinfarction before or during hospitalization. If apatient had more than one stroke during the studyperiod, we included only the first one. Stroke wasdefined according to criteria of the World HealthOrganization.5 Stroke types were defined based on

From the Department of Neurology, University of Vermont,Burlington, Vermont.

Address for reprints: Dr. Walter Bradley, Medical CenterHospital of Vermont, Department of Neurology, Brown 314,Burlington, VT 05405.

Received May 17, 1988; accepted November 2, 1989.

criteria of the Oxfordshire Community StrokeProject.6

Premature atherosclerosis was assumed if therewere two or more risk factors for atheroscleroticdisease in the absence of other identifiable causes ofcerebral infarction. These risk factors for atheroscle-rosis included hypertension (sustained systolic bloodpressure of > 160 mm Hg and diastolic blood pres-sure of >90 mm Hg for at least 1 week after thestroke), diabetes mellirus (history of the diseaserequiring drug or dietary treatment before thestroke), transient ischemic attacks, coronary arterydisease, hyperlipidemia (triglyceride concentrationof >160 mg%, cholesterol concentration of >230mg%, and/or high density lipoprotein concentrationof <35 mg%), smoking, and peripheral vasculardisease. Mitral valve prolapse (MVP) was diagnosedon the basis of published criteria for M-mode andtwo-dimensional echocardiographic images.7 Astroke was attributed to oral contraceptives if thewoman was using them at the time of the cerebralinfarction in the absence of other identifiable causes.A coagulation defect was defined as prolonged pro-thrombin, partial thromboplastin, or bleeding times.Criteria for migrainous stroke included a well-established history of migraine, a typical migraineheadache at the time of the acute stroke, and theabsence of other identifiable causes for the stroke.Alcohol was accepted as the cause for a stroke if thepatient had a history of excessive alcohol use and hadno other identifiable cause for the stroke.

Available data from computed tomography (CT),cerebral angiography, autopsy, cerebrospinal fluid

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Bevan et al Stroke in Young Adults 383

5 1

16-19 20-M 15-» 80-84 35-39 40-46

FIGURE 1. Bar graph. Demographic characteristics of 46young patients with intracerebral hemorrhage. Mean age was33.1 years. Shaded bars, females; filled bars, males; x axis, agegroups by years; y axis, number of patients.

IB-19 40 - 2 4 2S-

FIGURE 2. Bar graph. Demographic characteristics of 19young patients with subarachnoid hemorrhage. Mean age was35.5 years. Shaded bars, females; filled bars, males; x axis, agegroups by years; y axis, number of patients.

evaluation, 24-hour Holter monitoring, electrocar-diography, chest roentgenography, echocardiogra-phy, electroencephalography, and laboratory testswere reviewed. The laboratory tests included com-plete blood count; prothrombin, partial thromboplas-tin, and bleeding times; erythrocyte sedimentationrate; syphilis serology; collagen-vascular disease pro-file; glucose concentration; lipid profiles; lupus anti-coagulant assay; and others. Some clinical investiga-tions were not available in every patient.

ResultsA total of 113 young patients with stroke aged

15-45 years (63 males and 50 females) were admittedto the hospital during the 6 years. They comprised8.5% of the 1,331 patients of all ages admitted forstroke. The sex ratio among all 1,331 patients was1.29; 235 died. Most young patients (40%) were olderthan 40 years of age; their mean age was 35.0 years.

Forty-six young patients (41%, 25 males and 21females) sustained an ICH (Figure 1); these patientsrepresented 22.5% of the 204 patients of all agesadmitted with ICH. Table 1 shows the causes of ICHin these 46 young patients and the number who died.Among these 46 young patients, 13 were moderate toheavy drinkers of alcohol, six (one male and fivefemales) had a history of migraine, less than four hadthe ICH during pregnancy and the puerperium, andtwo were known users of cocaine and illicit drugs.Most ICHs (63%) were lobar, and most resulted

TABLE 1. Causes of Spontaneous Intracerebral Hemorrhage in 46Young Patients

Patients

from a ruptured aneurysm, or less commonly anarteriovenous malformation.

Nineteen young patients (17%, nine males and 10females) had an SAH (Figure 2); they comprised15.8% of the 120 patients of all ages admitted withSAH. Most SAHs were the result of a rupturedaneurysm; three patients died (Table 2). Six SAHpatients had a history of hypertension, and threewere moderate to heavy drinkers of alcohol.

Forty-eight young patients (42%, 29 males and 19females) had a cerebral infarction (Figure 3); thesepatients comprised 4.8% of the 1,007 patients of allages admitted with cerebral infarction. Almost half ofthese young patients were >40 years of age. Amongthe 18 patients <35 years old, the sex ratio was 0.8;among the 30 who were ^35 years old, it was 2.3. Thecauses of cerebral infarction in these young patientsare summarized in Table 3; a cause was identified inall but two patients. Of the 17 patients with cardio-embolic cerebral infarction, the underlying cardiacdisease was demonstrated in 11 and presumed in theother six from analysis of the clinical presentation,history, and CT results. MVP was the probable causeof cerebral infarction in two patients, one of whomwas an intravenous drug abuser. MVP was also foundin another patient but was not thought to be thecause of the cerebral infarction. Echocardiographywas performed in 25 of the 48 patients with cerebralinfarction, and the results were normal in 10. Pro-longed (24 hours) Holter monitoring was obtained insix patients and was normal in all six. Prematureatherosclerosis was implicated as the cause of thecerebral infarction in 15 patients (11 males and fourfemales, Table 3). Eight of the 15 had angiography;

Cause

Ruptured aneurysmRuptured arteriovenous malformationHypertensionTumorCoagulation abnormalityMoyamoya diseaseEclampsia

TotalDeaths

No.

21975211

4612

%

45.619.615.210.94.32.22.2

100.026.1

TABLE 2. Causes of Spontaneous Subarachnoid Hemorrhage in19 Young Patients

Cause

Ruptured aneurysmRuptured arteriovenous malformationVenous angioma

TotalDeaths

No.

1531

193

Patients

%

78.915.85.3

100.015.8

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384 Stroke Vol 21, No 3, March 1990

TABLE 4. Risk Factors for Atherosclerotic Vascular Disease in 15Young Patients With Cerebral Infarction

16-19 20-1* »S-19 90-34 38-39 40-46

FIGURE 3. Bar graph. Demographic characteristics of 48young patients with cerebral infarction. Mean age was 36.5years. Shaded bars, females; filled bars, males; x axis, agegroups by years; y axis, number of patients.

six angiograms were positive for carotid artery dis-ease, and the other two were normal. Risk factors foratherosclerotic cerebral infarction are summarized inTable 4. Nine of the 19 females with cerebral infarc-tion (47.4%) were receiving oral contraceptives.Other causes for the cerebral infarction were foundin seven, leaving two females with cerebral infarctionpresumed to be due solely to oral contraceptives. Thelupus anticoagulant was the presumed cause of threeembolic cerebral infarctions, all in females with sys-temic lupus erythematosus. Eight patients with cere-bral infarction (16.7%) were moderate to heavydrinkers of alcohol. In seven of these eight patients,other causes for the cerebral infarction were found,leaving one patient with cerebral infarction pre-sumed to be due solely to an alcoholic binge. Of thefive patients with cerebral infarction due to nonath-erosclerotic vascular disease, two had postoperativethromboemboli, one had thrombosis of the carotidartery after trauma to the neck and face, one had a

TABLE 3. Causes of Cerebral Infarction in 48 Young Patients

Cause

CardiacMural thrombusMitral valve prolapseAortic valve defectRheumatic heart diseaseCongenital heart diseasePresumed

Atherosclerotic occlusive diseaseHematologic

Oral contraceptivesLupus anticoagulantPregnancyAlcoholMultiple myeloma

Nonatherosclerotic vascular diseasePostoperative thromboembolusPosttraumatic arterial thrombusCarotid artery dissectionVasculitis

MigraineUnknown

TotalDeaths

Patients

No.

17422216

158

23111

52111

12

488

%

35.4

31.216.7

10.4

2.14.2

100.016.7

Risk factor

HypertensionSmokingDiabetes mellitusTransient ischemic attackCoronary artery diseaseHyperlipidemiaCarotid artery diseasePeripheral vascular diseaseFamily history

Males

1183356525

Females

422020211

Total

15105376736

carotid artery dissection, and another had vasculitisconfirmed by angiography and autopsy. Eighteenpatients with cerebral infarction had a history ofmigraine; in 17 there were other causes for thecerebral infarction, leaving only one patient diag-nosed as having a migrainous stroke.

DiscussionA cardiogenic cerebral embolus is one of the most

common causes of stroke in the young, accounting forup to one third of the cases.8-9 In our series, 35% ofthe cases of cerebral infarction were of cardiacorigin. The association between MVP and cerebralinfarction is of special importance in patients who donot have other risk factors for stroke. MVP must beaccepted as a cause of cerebral infarction since it isfound in 29-40% of young people with ischemicstroke but in only 7% of matched controls.10"12 In ourseries, echocardiography was not done in all patients,which raises the possibility that even more patientsmight have had MVP.

Premature cerebral atherosclerosis is generally theresult of risk factors for cerebrovascular disease suchas hypertension, diabetes mellitus, hyperlipidemia,and cigarette smoking. We found that 31% of theyoung patients with cerebral infarction had an ath-erosclerotic cause; the majority of these were >35years old. Our experience is similar to that in othersurveys.2-13-14

The use of oral contraceptives is associated with aninefold increased risk of cerebral infarction inwomen.15 The Collaborative Group for the Study ofStroke in Young Women found that the risk of strokewith the use of oral contraceptives rose sharply inwomen with hypertension or migraine and those whowere heavy smokers.1516 Oral contraceptives alterplatelet aggregation, enhance antithrombin III activ-ity, decrease serum antithrombin levels, and increasethe levels of certain coagulation factors, especiallyfactor VII.9 In our series, 47.4% of the women withcerebral infarction were using oral contraceptiveswhen their strokes occurred, but only two had strokesattributable solely to the oral contraceptives. It mustbe remembered that pregnancy increases the risk ofischemic events by approximately 13 times.17 The useof oral contraceptives, pregnancy, and the puerpe-

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Bevan et al Stroke in Young Adults 385

rium are often also implicated as causes of hemor-rhagic strokes. Five women among our youngpatients experienced strokes (four hemorrhagic andone ischemic) during pregnancy or the puerperium.

Alcohol contributes to stroke in several ways,including induction of cardiac arrhythmias and car-diac wall abnormalities (which predispose to cerebralembolism), induction of hypertension, enhancementof platelet aggregation, activation of the clottingcascade, reduction of cerebral blood flow by stimu-lating cerebral vascular smooth muscle contraction,and alteration of cerebral metabolism.18 A Finnishstudy suggested that alcohol was a frequent contrib-uting factor in the development of stroke19; in asurvey of patients with cerebral infarction, 40% hadbeen intoxicated during the previous 24 hours. Thisrate of recent alcohol abuse was 4-7 times that formales of similar ages in the general population and5-6 times that for females. The Honolulu HeartProgram noted that the risk of hemorrhagic strokedoubled for light drinkers and tripled for heavydrinkers compared with nondrinkers, independent oftheir hypertensive status.20 In our series, 24 (21.2%)of the patients were moderate to heavy drinkers ofalcohol: 13 had ICH, three had SAH, and eight hadcerebral infarction. Alcohol was the sole cause ofcerebral infarction in one patient.

Cerebral infarction is a potential complication ofmigraine headaches. The incidence of migraineamong young patients with stroke varies little fromthat among the general population (approximatelylS-30%).21-23 Spaccavento and Solomon24 found a27% incidence of migraine among young adults withstroke and attributed all of the strokes to migraine.In another study, Adams et al2 found that while 14%of their patients had a history of migraine, only 3% ofthe ischemic events were linked to migraine attacks.In our series, 18 patients (38% of those with cerebralinfarction) had a history of migraine, but in only one(2.1% of those with cerebral infarction) was migrainethe only cause of the stroke. Mechanisms by whichmigraine may produce stroke include vasospasm and/orarteriopathy, embolism, and platelet abnormalities.21-23

Patients with migraine have evidence of vasomotorinstability and platelet disturbances.21 CT and magneticresonance imaging (MRI) will demonstrate an infarct,but often the angiogram is normal. Rothrock et al25

prospectively evaluated 22 patients with acutemigraine-associated stroke and demonstrated cere-bral infarction or ICH by CT/MRI in 55% andabnormalities by cerebral angiography in 41% of thecases.

In our retrospective study, young patients com-prised 8.5% of all patients admitted with stroke, bothhemorrhagic and nonhemorThagic, 2.3 times that inthe National Survey of Stroke (3.7%).1 The propor-tion with ICH among our young stroke patients andstroke patients of all ages (41% and 15%, respec-tively) was higher than that calculated from Table 3.3of the National Survey of Stroke1 (37% and 12%,respectively). This may reflect the fact that the

Medical Center Hospital of Vermont is a regionalneurologic and neurosurgical referral center. Theratio of ICH to primary SAH in our series was almost2:1 for patients of all ages, while that in the NationalSurvey of Stroke1 was 1^1. The National Survey ofStroke probably underestimated the frequency ofICH since many patients were collected before theavailability of CT. The case-fatality rate in ouroverall series (17.7%) was less than that in theNational Survey of Stroke (23.9%), which may be dueto the higher proportion of young patients in ourseries.

Our study suggests that, although MVP, oral con-traceptives, alcohol, and migraine need to be consid-ered in patients with cerebral infarction and may berelatively frequent factors contributing to the devel-opment of a stroke, they are infrequent sole causes ofstroke in the young.

References1. Walker AE, Robins M, Weinfeld FD: Clinical findings. Stroke

2. Adams HP Jr, Butler MJ, Biller J, Toffol GJ: Nonhemorrhagiccerebral infarction in young adults. Arch Neurol 1986;43:793-796

3. Grundel AB, Cohen RJ, Saul RF, Taylor JR: Cerebral infarc-tion in young adults. Stroke 1978;9:39-42

4. Toffol GH, Biller J, Adams HP: Nontraumatic intracerebralhemorrhage in young adults. Arch Neurol 1987;44:483-485

5. Hatano S: Experience from a multicentre stroke-register, apreliminary report. Bull WHO 1986^4:541-553

6. Oxfordshire Community Stroke Project: Incidence of stroke inOxfordshire: First year's experience of a community strokeregister. Br Med J 1983;287:713-717

7. Morganroth J, Mardelli TJ, Naito M, Cher CC: Apical cross-sectional echocardiography: Standard for the diagnosis ofidiopathic mitral valve prolapse syndrome. Chest 1981;79:23-28

8. Hart RG, Freeman GL: Stroke in young people-The heart ofthe matter. West J Med 1987;146:596-597

9. Hachinslri V, Norris JW: The young stroke, in The AcuteStroke. Contemporary Neurology Series, vol 27. Philadelphia,FA Davis Co, 1985, pp 141-163

10. Kelley RE, Pina I, Lee S-C: Cerebral ischemia and mitral valveprolapse: Case-control study of associated factors. Stroke1988;19:443-446

11. Barnett HIM, Boughner DR, Taylor DW, Cooper DE, KostukWJ, Nichol PM: Further evidence relating mitral valve pro-lapse to cerebral ischemic events. N Engl J Med 1980;302:139-144

12. Kouvaras G, Bacoulas G: Association of mitral valve leafletprolapse with cerebral ischemic events in the young and earlymiddle-aged patient. QJ Med 1985^5:387-392

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15. Collaborative Group for the Study of Stroke in YoungWomen: Oral contraception and increased risk of cerebralischemia or thrombosis. N Engl J Med 1973;288:871-878

16. Collaborative Group for the Study of Stroke in YoungWomen: Oral contraceptives and stroke in young women,associated risk factors. JAMA 1975;231:718-722

17. Wiebers DO: Ischemic cerebrovascular complications of preg-nancy. Arch Neurol 1985;42:1106-1113

18. Gorelick PB: Alcohol and stroke. Curr Concepts CerebrovascDis Stroke 1986;21:21-25

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20. Donahue RP, Abbott RD, Reed DM, Yano K: Alcohol and 23. Waters WE: Epidemiology of Migraine. Brachnell, UK, Boeh-hemorrhagic stroke. The Honolulu Heart Program. JAMA ringer Ingelheim, 19741986;255:2311-2314 24. Spaccavento LJ, Solomon GD: Migraine as an etiology of

21. Henrich JB: The association between migraine and cerebral stroke in young adults. Headache 1984;24:19-22vascular events: An analytic review. / Chronic Dis 1987; 25. Rothrock JF, Walicke P, Swenson MR, Lyden PD, Logan WR:40:329-335 Migrainous stroke. Arch Neuwl 1988;45:64-67

22. Henrich JB, Sandercock PAG, Warlow CP, Jones J-N: Strokeand migraine in the Oxfordshire Community Stroke Project. /Neuwl 1986^33:257-262 KEY WORDS • cerebrovascular disorders • young adults

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H Bevan, K Sharma and W BradleyStroke in young adults.

Print ISSN: 0039-2499. Online ISSN: 1524-4628 Copyright © 1990 American Heart Association, Inc. All rights reserved.

is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231Stroke doi: 10.1161/01.STR.21.3.382

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