13ournal of NeurologAy, Neurosurgery, and Psychiatry 1995;59:132-137

Comparison of CT in patients with cerebralischaemia with or without non-rheumatic atrialfibrillation

Jeanette C van Latum, Peter J Koudstaal, L Jaap Kappelle, Fop van Kooten, Ale Algra,Jan van Gijn, for the European Atrial Fibrillation Trial and Dutch T I A Trial StudyGroups

AbstractIn an attempt to distinguish between theCT characteristics of strokes ofpresumedcardioembolic origin and strokes causedby arterial disease, a comparison wasmade between the baseline CT of twoprospective cohorts of patients with tran-sient ischaemic attack or minorischaemic stroke, with (n = 985) or with-out (n = 2987) non-rheumatic atrial fib-rillation (NRAF). Of the patients withNRAF 54% had evidence of cerebralinfarction v 41% of the controls (patientswith sinus rhythm (SR); odds ratio (OR)1-7; 95% confidence interval (95% CI)1 4-19). Patients with NRAF more oftenhad multiple infarcts (OR 1-4; 95% CI1-1-1*8), and more often infarcts thatwere not related to current neurologicalsymptoms (OR 1-5; 95% CI 1-2-1*8). Forsymptomatic infarcts, patients withNRAF more often had cortical end zoneinfarcts (OR 3-1; 95% CI 26-3*8) and cor-tical border zone infarcts (OR 1-9; 95%CI 1.3-2.9) than patients with SR.Conversely, symptomatic small deepinfarcts (lacunae) were more often seenin patients with SR (OR 3 9; 95% CI2*8-5*4). Multivariate analyses showedthat all these findings were independentof differences in baseline characteristicsbetween the two study groups. The CTcharacteristics overlapped and did notallow a reliable distinction between car-dioembolic and atherosclerotic causes ofstroke in patients with NRAF.

( Neurol Neurosurg Psychiatry 1995;59:132-137)

University HospitalRotterdam Dijkzigt,The NetherlandsJ C van LatumP J KoudstaalF van Kooten

University HospitalUtrecht, TheNetherlandsL J KappelleA AlgraJ van GijnCorrespondence to:Dr Peter J Koudstaal,Department of Neurology,University HospitalRotterdam Dijkzigt; 40 DrMolewaterplein; 3015 GDRotterdam, TheNetherlands.

Received 9 November 1994and in revised form24 March 1995Accepted 30 March 1995

Keywords: computed tomography; cerebral ischaemia;non-rheumatic atrial fibrillation; cardioembolism;thromboembolism

Although the role of non-rheumatic atrial fib-rillation (NRAF) as a risk factor for stroke hasbeen well established by several epidemiologi-cal studies,' 2 the pathogenesis of strokesrelated to NRAF continues to be uncertain.The presence of NRAF in itself is insufficientevidence of cardiogenic embolism to thebrain, as NRAF might also be a mere markerof coexistent atherosclerotic disease, presentin a large percentage of the elderly population.Both direct and indirect arguments, however,support a more causal relation between atrialfibrillation and cerebral ischaemic episodes. Adistinct clustering of ischaemic episodes is

seen around the time of onset of atrial fibrilla-tion,34 the rate of embolism in patients withthyrotoxic atrial fibrillation can be as high as30%,j and epidemiological studies indicate afourfold to 10-fold increased risk of stroke inpatients with non-rheumatic atrial fibrillation,without a concomitant increase in risk ofischaemic heart disease.67

Because prognosis and choice of secondarypreventive treatment possibly differ accordingto whether the suspected cause of the stroke isof arterial or cardiac origin, the distinction isimportant in individual cases. Numerous clas-sification schemes have been proposed thatare based on a combination of clinical, labora-tory, and sometimes, pathology data, and aremostly derived from literature reviews.89These classification schemes usually includetypical CT characteristics (for example, largeischaemic lesions with cortical involvement,multiple lesions in different vascular territo-ries, isolated posterior infarcts), that mighthelp to distinguish between cerebral infarctscaused by embolism from the heart orembolism from vessel walls that have beendamaged by atherosclerotic degeneration inpatients with NRAF. These criteria are basedon few studies that have actually assessed CTdifferences between cardioembolic andthromboembolic stroke. Most studiesincluded patients with sources of cardiacembolism other than NRAF-for instance,patients with rheumatic heart disease, pros-thetic valves, or recent myocardial infarc-tion.'1 13 Studies focusing specifically on CTcharacteristics of stroke patients with non-rheumatic atrial fibrillation were usuallysmall'4 17 and most did not provide a compari-son with CT in stroke patients without atrialfibrillation.'4 17We have compared the CT characteristics

in two prospectively studied cohorts ofpatients with transient ischaemic attack orminor ischaemic stroke, with (n = 985) orwithout (n = 2987) non-rheumatic atrial fib-rillation.

Patients and methodsDetails on CT characteristics of patients withNRAF presenting with symptoms of transientischaemic attack or minor ischaemic strokewere derived from a cohort of 1007 of thesepatients that were studied in the EuropeanAtrial Fibrillation Trial, a multicentre ran-domised clinical trial assessing the value oforal anticoagulants and aspirin in the sec-ondary prevention of vascular complications.'8

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Five patients were excluded from the analysisbecause their scan showed evidence of a cere-bral tumour (one patient), a primary intrac-erebral haemorrhage (one patient), or becausethey had no evidence of atrial fibrillation(three patients). In another 17 patients no CTwas available, leaving 985 scans for analysis.The control group, in which we also analysedCT, consisted of 2987 patients in sinusrhythm (SR) who had no known potentialsource of cardiac embolism and who had alsopresented with transient ischaemic attacks ornon-disabling ischaemic strokes. These con-trol patients were part of a study cohort of3150 patients randomised in the Dutch TIATrial, a study which aimed to investigate theprotective effects of low dose aspirin andatenolol in transient ischaemic attack andpatients with minor ischaemic stroke.'9Twenty three patients of this cohort had beenincorrectly entered (no cerebral ischaemia)and another nine were known to have atrialfibrillation. Of the remaining 3118 patients,no CT was available in 131.

For both study populations, CT wasmandatory at study entry (except for patientswith transient monocular blindness in theDutch TIA Trial) and patients had to be ran-domised within three months of their (last)cerebrovascular event. The scans of bothpatient groups were independently reviewedby at least two neurologists from a group offour investigators who used the same protocolfor both studies. Visible infarcts were classi-fied according to gross location (left or righthemisphere or posterior fossa), vascular terri-tory,20 and to whether or not the cortex wasinvolved. Subcortical infarctions were furtherclassified as being small (S 15 mm) or large(> 15 mm). Small subcortical (lacunar)infarctions were considered indicative of smallvessel disease; all other ischaemic lesions

Table 1 Comparison of CTfindings in patients with a recent transient ischaemic attackor minor ischaemic stroke, with sinus rhythm (SR) or with non-rheumatic atrialfibrillation (NRAF)

Sinus rhythm AtrialfibrillationBrain CT characteristics (n = 2987) (n = 985)White matter hypodensity 333 (11) 165 (17)

Moderate 238 (8) 133 (14)Severe 95 (3) 32 (3)

No ischaemic lesions on CT 1748 (59) 453 (46)Single ischaemic lesion 985 (33) 417 (42)Not related to qualifying event 219 (7) 91 (9)Uncertain relevancy 24 (1) 10 (2)Symptomatic 742 (25) 316 (32)

Cortical end zone 227 (8) 182 (18)Cortical border zone 49 (1) 28 (3)Cerebellar or brain stem 33 (1) 17 (2)Large subcortical 112 (4) 53 (5)Small subcortical 321 (11) 36 (4)

Multiple ischaemic lesions 254 (9) 115 (12)All non-related 31 (1) 24 (2)Uncertain relevancy 3 (< 1) 4 (< 1)One symptomatic lesion 220 (7) 87 (9)

Cortical end zone 42 (1) 50 (5)Cortical border zone 17 (< 1) 13 (1)Cerebellar or brain stem 9 (< 1) 9 (1)Large subcortical 25 (1) 8 (1)Small subcortical 127 (4) 7 (1)

Infarcts in multiple territories 198 (7) 97 (10)Only small vessel disease 115 (4) 13 (1)Only large vessel disease 66 (2) 60 (6)Both small and large vessel 73 (2) 42 (4)No prior cerebrovascular events in the

past year 170 (6) 81 (8)

Column percentages are given in parentheses.

(large subcortical, end zone, and border zoneinfarctions) were presumed to be associatedwith large vessel disease. White matter hypo-density with ill defined borders was inter-preted and recorded as periventricularleukoencephalopathy.2' Scans with multipleinfarcts that could not be explained by occlu-sion of a single intracerebral artery or itsbranches and those showing multiple borderzone infarcts, or border zone infarcts in com-bination with cortical infarcts in vascular terri-tories not involved in the border zone area,were regarded as indicating involvement ofmultiple territories. During the auditing pro-cedure clinical details were not given until therelevance of the recorded CT abnormalitieshad to be assessed. Focal hypodensities ofpresumably vascular origin that were notrelated to the qualifying event were classifiedas non-related ischaemic lesions. No attemptwas made to blind reviewers for the allocationof the patients (SR or NRAF). Baseline infor-mation on both groups had been prospectivelyobtained at study entry on standardisedforms. Although different forms were used forthe two studies, the information about thepresence of major vascular risk factors such ashypertension, diabetes mellitus, hypercholes-terolaemia, previous cardiovascular events orsurgery, angina pectoris, intermittent claudi-cation, and current smoking was recordedaccording to the same criteria. Information onclinical features, functional disability, dura-tion of neurological deficits, and ancillaryinvestigations (cardiothoracic ratio, glucoseconcentrations, and packed cell volume) alsosatisfied the same criteria. In the sinus rhythmgroup no systematic information was obtainedon the presence of carotid artery disease; norwas echocardiography routinely performed.

Data were analysed with the statisticalpackage for social sciences (SPSS), Epistatand EGRET statistical software. Differencesin CT and baseline characteristics betweenthe two study groups were evaluated by x2 testfor categorial data and a t test for continuousdata. Comparisons were expressed as oddsratios (ORs) with the corresponding 95%confidence intervals (95% CIs). Multivariatelogistic regression analyses were performed toassess whether differences in CT characteris-tics could be attributed to differences in base-line characteristics.

ResultsThe total group of patients studied comprised1524 (37%) women and 2596 (63%) men.The mean age was 66-9 (SD 10) years with aminimum age of 29 and a maximum age of96.

FREQUENCY OF ISCHAEMIC LESIONSTable 1 lists the CT characteristics in patientswith NRAF and SR. Of the CT available foranalysis (n = 3972), 2201 (55%) showed noevidence of ischaemic infarction. The per-centage of normal scans was smaller in theNRAF group (46%) than in the SR group(59%) (OR 0-6; 95% CI 0-5-0 7), despite

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Companison ofCTcharacteristics betweenpatients with ischaemicstroke with non-rheumaticatrialfibrillation or sinusrhythm. Horizontal linesrepresent 95% CIs. Dottedlines represent ORs and95% CIs after adjustingfor differences in baselinecharacteristics.

Any infarct

Symptomatic infarct

Non-related infarct

Multiple territories

Symptomatic cortical

Symptomatic border zone

Symptomatic cerebellaror brainstem

Symptomatic subcortical(>15 mm)

Symptomatic small deep --

0 0.5

.____F-.I.

-__-_ ----_ -__

.-___ ___ _______________I

-----1-I-----

1.5 2-0 2.5 3.0 3.5Odds ratio

More common More commonin in

sinus rhythm NRAF

18% of the scans in the NRAF group havingbeen made within 24 hours of the onset ofneurological symptoms, v 8% in the SRgroup. Patients with NRAF more often hadmultiple ischaemic lesions visible on theirscans (12%) than patients with SR (9%) (OR1-4; 95% CI 1-1-1.8). Of the patients withmultiple ischaemic lesions, more than onevascular territory was involved in 84% (79%for patients with SR). In keeping with thisfinding patients with NRAF more often hadinfarcts on CT that could not be ascribed totheir current neurological symptoms (20% v15%; OR 1-5; 95% CI 1-2-1-8). Comparedwith patients with SR, patients with NRAFmore often had only large vessel infarcts onCT than only small vessel lesions (OR 5-1;95% CI 3-9-6&6).

White matter hypodensity was found in17% of all patients with only small vesselinfarcts v 10% of the patients with only largevessel infarcts (OR 1-8; 95% CI 1A4-2-4), butthis association was stronger in patients withSR (OR 2-7; 95% CI 1-8-4-0) than in patientswith NRAF (OR 1 1; 95% CI 0-6-2-2).Isolated infarcts in the territory of the poste-rior cerebral artery were more often seen inpatients with NRAF (OR 1 8; 95% CI1 3-2-5).

TYPE OF SYMPTOMATIC INFARCTION (FIGURE)Patients with NRAF more often had sympto-matic cortical end zone infarcts (24% v 9%;OR 3-1; 95% CI 2-6-3 8) and symptomaticcortical border zone infarcts (4% v 2%; OR1-9; 95% CI 1-3-2-9) than patients with SR.Symptomatic cerebellar or brainstem lesionsalso occurred more often in patients withNRAF (4% v 1%; OR 1L9; 95% CI 1-2-3-1).For symptomatic subcortical infarcts, smalldeep (lacunar) lesions were more often found

in patients with SR (15% v 4%; OR 3T9; 95%CI 2.8-5-4), whereas in patients with NRAFlarge subcortical infarcts (> 15 mm) weremore common (6% v 5%; OR 1-4; 95% CI1 *0-1 *9).

NON-RELATED INFARCTSPatients with NRAF more often had infarctson CT that could not be ascribed to the quali-fying symptoms (OR 1-5; 95% CI 1.2-1-8).In the patients with SR, 434 had evidence ofprevious stroke (14%). These patients had atotal of 500 currently asymptomatic infarcts,67% of which were small and deep (lacunar),16% cortical, 7% large subcortical, 7% borderzone, and 3% in the cerebellum or brain stem.In the NRAF group, 197 patients had evi-dence of previous stroke on CT (20%). Thirtysix per cent of the total 240 currently asymp-tomatic ischaemic lesions were of the smalldeep (lacunar) type, 37% were cortical, 9%large subcortical, 10% border zone, and 8%were in the cerebellar cortex or the brainstem. Thirty three per cent of the patientswith NRAF and 31% of the patients with SRwith non-related infarct(s) on CT hadreported cerebrovascular symptoms in theyear before study entry. Another 2% of thepatients with NRAF had had symptomaticcerebrovascular events before that time; thisinformation was not available for patients inthe SR group.

BASELINE CHARACTERISTICSTable 2 shows that there were some differ-ences in baseline characteristics betweenpatients with NRAF and those with SR, mostof which were significant because of the largenumbers of patients studied. Patients withNRAF were older and more often female.With the exception of smoking habits, well

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Table 2 Comparison of baseline characteristics in patients with a recent transientischaemic attack or minor ischaemic stroke, with and without non-rheumatic atrialfibrillation

Baseline characteristics

SR (n = 3118) NRAF (n = 1002)

Demographics:Male 65-3 55.8***Age (y (SD)) 65-1 (10) 72-7 (8)***

Neurological state:Symptoms lasted < 24 hours 31 9 22 9***Rankin grade > 1 at study entry3' 21 5 41.3***CT available 95 8 98-3***CT made within 24 hours 7-8 17-8***

History of vascular events:Prior myocardial infarction 9-8 8-1Vascular surgery 1 5 2-4Cerebrovascular events in the past year 31 5 22-0***

Vascular risk factors:History of hypertension 41 9 47 0***Hypercholesterolaemia 3 7 9 6***Diabetes 7 9 12 9***Current regular smoking 44 8 18.8***Angina pectoris 9 3 10 9***Intermittent claudication 5 0 4-2

Additional investigations:Systolic blood pressure > 160 mm Hg 35-5 19-7***Diastolic blood pressure > 100 mm Hg 14 5 5 0***Packed cell volume > 0-45 1/1 39-6 29-1***Glucose > 7O0 mmol/l 15-7 16 9Cardiothoracic ratio on chest radiograph> 0 50 10-2 23-5***

***p < 0-001.

known vascular risk factors such as a historyof hypertension or diabetes were present moreoften in patients with NRAF. Measured bloodpressures at study entry, however, were signif-icantly lower in the NRAF group (mean sys-tolic blood pressure 158 mm Hg in patientswith SR and 148 mm Hg in patients withNRAF, mean diastolic blood pressure 91 mmHg and 86 mm Hg; t test p < 0-0001 forboth). A remarkable difference between thetwo groups was the high rate of hypercholes-terolaemia in patients with NRAF (9-6% v3-7%). This probably reflects the differencebetween a multinational European patientcohort (the patients with NRAF) and a Dutchcohort of patients (SR group), an explanationconfirmed by the finding that of the Dutchpatients with NRAF (n = 187) only 3-7% hadhypercholesterolaemia. When only Dutchpatients with NRAF were compared withtheir counterparts with SR all other reporteddifferences in baseline characteristics wereconfirmed but the absolute differences wereslightly smaller in all instances and did notalways reach significance. Cardiomegaly(defined as a cardiothoracic ratio > 0 50 onchest radiographs) was more often found inpatients with NRAF (OR 2-7; 95% CI2 3-3 3). All reported differences in CT char-acteristics between patients with SR and thosewith NRAF remained essentially the sameafter adjustment for differences in baselinecharacteristics. In both study groups, 50% ofall patients with only small vessel disease had ahistory of hypertension v 43% of the patientswith only large vessel involvement (OR 1 4;95% CI 1 1-1-7), and 40% of the patientswithout infarcts on CT (OR 1-5; 95% CI1-3-1-8).

Patients with NRAF less often showedcomplete recovery within 24 hours thanpatients with SR (22-9% v 31-9%; OR 0-6;95% CI 0 5-0-8). Accordingly, the Rankin

grade for handicap at study entry was 2 orover in 41% of the patients with NRAF v 21%of the patients with SR (OR 2-6; 95% CI2 2-3O0).

SPECIFICITY OF CT CHARACTERISTICSOn the premise that the mere presence ofNRAF alone is not sufficient for the diagnosisof cardioembolic stroke, we assessed whethercertain CT characteristics were associatedwith NRAF rather than with SR. For patientswith visible infarcts on their CT, the least typ-ical finding in patients with SR was the pres-ence of multiple large vessel infarcts indifferent vascular territories and isolated pos-terior artery infarcts that were found in only4% and 8% respectively of these patients.Unfortunately these characteristics alsooccurred in a few patients with NRAF (9%and 1 1% respectively).

Fifty one per cent of patients with SR withvisible ischaemic lesions on CT had onlyinfarcts (single or multiple; symptomatic ornon-related) of the small deep type, a findingoccurring in only 17% of the patients withNRAF.

DiscussionThis study shows that patients with a tran-sient ischaemic attack or minor ischaemicstroke in combination with NRAF relativelyoften have (a) large infarcts (> 15 mm), eithercortical or subcortical; (b) infarcts in differentvascular territories; (c) currently asympto-matic infarcts; and (d) isolated infarcts in theterritory of the posterior cerebral artery.These differences accord with the most com-monly used criteria for cardioembolicstroke.10'72223 Despite these significant differ-ences in CT features between NRAF and SR,the characteristics, alone or in combination,overlap and do not in individual cases allow areliable distinction as to whether the presenceof NRAF is causal or incidental. In patientswith ischaemic lesions on their scan, thesocalled typically cardioembolic CT features(large infarcts in different arterial territories,and isolated infarcts in the territory of theposterior cerebral artery) were indeed foundin only a few stroke patients in sinus rhythm(4% and 8% in our series, respectively), butalso in only 9% and 1 1% of our patients withNRAF.A weakness of our study is the problem of

potential selection bias, which may haveoccurred in both study populations. Forinstance, patients with atrial fibrillation weremore likely to be entered into the EuropeanAtrial Fibrillation Trial if they had conven-tional evidence of cardiogenic embolism suchas a cortical infarct or infarcts in multiple terri-tories, and less likely if they showed a lacunarinfarct. Such preselection could explain atleast part of the differences between groups.The finding that isolated infarcts in the terri-tory of the posterior cerebral artery were morecommon in patients with atrial fibrillationmay represent another example of selectionbias in that transient hemianopia is rarely

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reported as a transient ischaemic attack andonce infarction has occurred in the occipitalcortex vision rarely recovers so "minor"occipital strokes are uncommon. Further-more, patients with severe carotid stenosis arelikely to have been excluded from the DutchTIA Trial, although carotid stenosis orplanned carotid endarterectomy was not anexclusion criterion. In a future study, we willexamine differences between patients enteredinto the European Atrial Fibrillation Trialwith carotid territory symptoms and patientsin sinus rhythm with severe carotid stenosis inthe European Carotid Surgery Trial.A CT feature that is usually thought to be

typical for atherosclerotic small vessel diseaseis the presence of only small deep (lacunar)infarction. Our study shows that infarcts inthe territory of the penetrating arteries occa-sionally occur in patients with NRAF, asreported by previous studies,24 25 but theseusually involve more than one penetratingartery. Lacuae, which are thought to becaused by (local) obstruction of a single pene-trating artery and which are often associatedwith arterial hypertension, were seen signifi-cantly more often in the SR population. Asmany as 17% of the patients with NRAF withvisible ischaemic lesions on CT, however, hadonly small deep infarcts (v 51% of the patientswith SR). In 36% of the patients with NRAFand in 29% of patients with SR with multipleischaemic lesions, small deep infarcts wereseen together with the larger infarcts.Although hypertension was present signifi-cantly more often in patients with only smallischaemic lesions on CT than in patients withonly large ischaemic lesions both in patientswith NRAF and those with SR, the absolutedifference (50% v 43%) was not impressive,as found earlier.26 These findings might sug-gest that there is no direct causal relationbetween NRAF and lacunar infarcts, and thattheir coexistence should be considered as twodifferent expressions of atherosclerosis in thesame patient. Alternatively, atrial fibrillationcan be the direct cause of lacunar infarcts in asmall percentage of patients.An important drawback of the presented

study is the lack of a gold standard with whichto distinguish between infarcts caused by car-diac emboli, emboli from vessel walls withatherosclerotic plaques, or local small vesselocclusion. Even with additional informationfrom carotid angiography and echocardiogra-phy, one can only guess at the most probableunderlying pathogenesis of an ischaemicevent. There is a great overlap in the type andsize of infarcts caused by cardiogenic emboliand those caused by arterial disease.27 29 Inpart the modest discriminatory value of CTfor the current study group may also beexplained by the selection of patients that hadonly minor or transient neurological symp-toms. Possibly, because of this selection, thesource of embolism in patients with NRAFwas often in the arterial system (causingsmaller infarcts) and not in the heart, otherthan in the entire population of stroke patientswith NRAF.

For baseline characteristics, one of themost striking findings was that of lower sys-tolic and diastolic blood pressure measure-ments at study entry in the NRAF group thanin the SR group, despite the fact that patientswith NRAF more often had a history ofhypertension. Because patients with NRAFcould be randomised to anticoagulant treat-ment, poorly controlled patients were mostlyexcluded and extra care might have beentaken to achieve proper control of blood pres-sure. On the other hand, the lower diastolicblood pressure in patients with NRAF couldreflect a more progressive state of atheroscle-rotic disease with stiffening of the vesselwall.30 A more plausible explanation would bethe difficulty of obtaining consistent bloodpressure measurements in patients withNRAF. The other differences in baselinecharacteristics between patients with NRAFand those with SR (more often female, moreoften diabetic, less often current smoking) canmostly be attributed to the higher mean age ofthe patients with atrial fibrillation. The higherprevalence of cardiomegaly in patients withNRAF probably reflects a longstanding his-tory of hypertension, chronic atrial fibrilla-tion, or both. Neurological deficits tended tolast longer and be more severe in patients withNRAF than in those with SR, which is inagreement with the finding that CT patientswith NRAF more often showed cerebralinfarcts in general, and large infarcts in partic-ular. It might also explain why patients withSR had more often reported ischaemic eventsin the past. Patients with NRAF who had hadearlier events would have been too disabled toenter the trial.The results of CT comparisons reported in

this study may have been biased because thereviewers were aware whether patients had SRor NRAF. On the other hand, these reviewswere intended to establish a baseline registerfor each of the two trials, and not to comparethe two groups. Another potential source ofbias might have been the fact that CT in theDutch TIA Trial was earlier, between 1986and 1989, and therefore may have been oflesser quality than the European AtrialFibrillation Trial (1988-92). If this hadindeed been a problem fewer small deepinfarcts (sometimes difficult to distinguish onsecond generation CT) would have beenfound in the SR group; this was not the case.Finally, in interpreting all significantdifferences between NRAF and SR groups,both of CT and baseline characteristics, oneshould keep in mind that because of the largestudy size even small differences become sig-nificant but that the clinical relevance of manyof these reported differences is not alwaysclear.We conclude that, although there are strik-

ing differences in CT features betweenpatients with stroke with or without non-rheumatic atrial fibrillation, these differencesare of little help within the group of patientswith NRAF in distinguishing between strokesof presumed cardioembolic origin and strokescaused by arterial disease.

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This work was supported by grants from the NetherlandsHeart Foundation (grants 84-089; 87-048; 88-210); grant28-1732 from the Praeventiefonds, The Netherlands; BayerWuppertal, Germany; ICI Pharmaceuticals in TheNetherlands and the United Kingdom; the UK StrokeAssociation, United Kingdom; ASTA, The Netherlands;University Hospital Utrecht; and University HospitalRotterdam, The Netherlands. A list of collaborators in theEuropean Atrial Fibrillation Trial appears in the Lancet1993;342: 1255-62 and a list of collaborators in the Dutch TIATrial appears in the NEnglJ'Med 199 1;325:1261-66.

1 Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation: amajor contributor to stroke in the elderly, theFramingham study. Arch Intern Med 1987;147:1561-4.

2 Wolf PA, Dawber TR, Thomas HE, Kannel WB.Epidemiological assessment of chronic atrial fibrillationand risk of stroke: the Framingham study. Neurology1978;28:973-7.

3 Cerebral Embolism Task Force. Cardiogenic embolism.Arch Neurol 1986;43:71-84.

4 Petersen P, Godtfredsen J. Embolic complications inparoxysmal atrial fibrillation. Stroke 1986;17:622-6.

5 Cerebral Embolism Task Force. Cardiogenic brainembolism: the second report of the Cerebral EmbolismTask Force. Arch Neurol 1989;46:727-43.

6 Boysen G, Nyboe J, Appleyard M, et al. Stroke incidenceand risk factors for stoke in Copenhagen. Denmark.Stroke 1988;19:1345-53.

7 Brand FN, Abbott RD, Kannel WB, Wolf PA.Characteristics and prognosis of lone atrial fibrillation,30-year follow-up in the Framingham study. JAMA1985;254:3449-53.

8 Foulkes MA, Wolf PA, Price TR, Mohr JP, Hier DB. Thestroke data bank: design, methods, and baseline charac-teristics. Stroke 1988;19:547-54.

9 Ramirez-Lassepas M, Cipolle RJ, Bjork RJ, et al. Canembolic stroke be diagnosed on the basis of neurologicalclinical criteria? Arch Neurol 1987;44:87-9.

10 Bogousslavsky J, Cachin C, Regli F, Despland P-A, vanMelle G, Kappenberger L, for the Lausanne StrokeRegistry Group. Cardiac sources of embolism and cere-bral infarction-clinical consequences and vascular con-comitants: the Lausanne Stroke Registry. Neurology199 1;41:855-9.

11 Bogousslavsky J, van Melle G, Regli F. The LausanneStroke Registry: analysis of 1,000 consecutive patientswith first stroke. Stroke 1988;19:1083-92.

12 Caplan LR, Hier DB, D'Cruz I. Cerebral embolism in theMichael Reese Stroke Registry. Stroke 1983;14:530-6.

13 Olsen TS, Skriver EB, Herning M. Cause of cerebralinfarction in the carotid territory. Its relation to the sizeand the location of the infarct and to the underlying vas-cular lesion. Stroke 1985;16:459-66.

14 Bogousslavsky, van Melle G, Regli F, Kappenberger L.

Pathogenesis of anterior circulation stroke in patientswith nonvalvular atrial fibrillation: the Lausanne StrokeRegistry. Neurology 1990;40:1046-50.

15 D'Olhaberriague L, Hemrndez-Vidal A, Molina L, et al. Aprospective study of atrial fibrillation and stroke. Stroke1989;20: 1648-52.

16 Harrison MJG, Marshall J. Atrial fibrillation, TIAs andcompleted strokes. Stroke 1984;15:441-2.

17 Miller VT, Rothrock JF, Pearce LA, Feinberg WM, HartRG, Anderson DC, on behalf of the Stroke Preventionin Atrial Fibrillation investigators. Ischemic stroke inpatients with atrial fibrillation: effect of aspirin accordingto stroke mechanism. Neurology 1993;43:32-6.

18 EAFT Study Group. Secondary prevention in non-rheumatic atrial fibrillation after transient ischaemicattack or minor stroke. Lancet 1993;342:1255-62.

19 Dutch TIA Trial Study Group. A comparison of two dosesof aspirin (30 mg vs. 283 mg a day) in patients after atransient ischemic attack or minor ischemic stroke.NEngljMed 1991;325:1261-6.

20 Damasio H. A computed tomographic guide to the identi-fication of cerebral vascular territories. Arch Neurol 1983;40:138-42.

21 Van Swieten JC, Hijdra A, Koudstaal PJ, van Gijn J.Grading white matter lesions on CT or MRI; a simplescale. 7 Neurol Neurosurg Psychiatry 1990;53: 1080-3.

22 Kempster PA, Gerraty RP, Gates PC. Asympatomaticcerebral infarction in patients with chronic atrial fibrilla-tion. Stroke 1988;19:955-7.

23 Petersen P, Madsen EB, Brun B, Pedersen F, GyldenstedC, Boysen G. Silent cerebral infarction in chronic atrialfibrillation. Stroke 1987;18:1098-100.

24 Ghika J, Bogousslavsky J, Regli F. Infarcts in the territory ofthe deep perforators from the carotid system. Neurology1989;39:507-12.

25 Santamaira J, Graus F, Rubio F, Arbizu T, Peres J.Cerebral infarction of the basal ganglia due to embolismfrom the heart. Stroke 1983;14:911-4.

26 Van Gijn J, Kraaijeveld CL. Blood pressure does not predictlucunar infarction. J Neurol Neurosurg Psychiatry 1982;45:147-50.

27 Millikan C, Futrell N. The fallacy of the lacune hypothe-sis. Stroke 1990;21:1251-7.

28 Lodder J, Bamford JM, Sandercock PAG, Jones LN,Warlow CP. Are hypertension or cardiac embolism likelycauses of lucunar infarction? Stroke 1990;21:375-81.

29 Merwijk van G, Lodder J, Bamford J, Kester ADM. Howoften is non-valvular atrial fibrillation the cause of braininfarction? Jf Neurol 1990;237:205-7.

30 Witteman JCM, Grobbee DE, Valkenburg HA, et al. J-shaped relation between change in diastolic blood pres-sure and progression of aortic atherosclerosis. Lancet1994;343:504-7.

31 Van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJA,van Gijn J. Interobserver agreement for the assessmentof handicap in stroke patients. Stroke 1988;19:604-7.

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