Similarities to Large Artery Vs Small Artery Disease

ORIGINAL CONTRIBUTION The Course of Patients With Lacunar Infarcts and a Parent Arterial Lesion Similarities to Large Artery vs Small Artery Disease

Oh Young Bang, MD, PhD; Sung Yeol Joo, MD; Phil Hyu Lee, MD; Uk Shik Joo, MD; Jae Hyuk Lee, MD; In Soo Joo, MD; Kyoon Huh, MD

Background: The significance of occlusive lesions of Main Outcome Measures: Recurrent strokes and the the parent artery in patients with lacunar syndrome (LS) prognosis were registered for 1 year, and the outcome and small deep infarcts (SDIs) on diffusion-weighted im- of the PAD group was compared with that of the SAD aging remains unclear. and LAD groups.

Objective: To compare the recurrence of stroke in pa- Results: During follow-up, there were 9 deaths (6 vas- tients with LS and SDIs between those with vs without a cular) and 18 recurrent strokes. The recurrence rate in parent arterial lesion. the PAD group (16%) was significantly higher than that in the SAD group (1%) (P=.01) but similar to that in the Design: Analysis of data from a prospective acute stroke LAD group (17%) (P=.87). The presence of the parent registry. arterial lesion was the only independent predictor of stroke recurrence in patients with LS and SDIs (odds ratio, 13.8; Setting: University hospital. 95% confidence interval, 1.5-123.9; P=.02).

Patients: Using clinical syndrome, diffusion-weighted Conclusions: Although LS on examination, SDIs on dif- imaging, and vascular studies, we divided 173 patients fusion-weighted imaging, and a stable hospital course sug- into 3 groups: (1) parent arterial disease occluding deep gest lacunar stroke of benign course, our results indicate perforators (PAD), LS with SDIs, and a parent arterial le- that the PAD group represents an intracranial type of LAD. sion (n=32); (2) small artery disease (SAD) (n=70); and (3) large artery disease (LAD) (n=71). Arch Neurol. 2004;61:514-519

ACUNAR STROKES, THAT IS, LA- However, middle cerebral artery cunar syndrome (LS) with (MCA) stenosis is recognized increas- symptomatic small deep in- ingly in patients with SDIs.10,11 Previ- farcts (SDIs) on neuroimag- ously, Madden et al12 reported that ap- ing, are associated with low proximately one third of patients who were mortalityL rates and low stroke recur- initially diagnosed as having small artery rence rates in hospital- and community- disease (SAD), based on clinical features based studies.1-7 Moreover, intracranial ste- and baseline computed tomographic find- nosis has been reported to be a negligible ings, had abnormalities on diagnostic study cause of SDI.8 For these reasons, physi- and suggested that a careful evaluation of cians treating patients with LS and SDIs the etiology is justified in all patients with are apt to be negligent in investigating the stroke, regardless of the presumed sub- underlying cause, such as parent arterial type. In a previous study by our group,13 disease (PAD). In fact, in the TOAST (Trial we recently found that atherosclerotic of ORG 10172 in Acute Stroke Treat- MCA lesions were a common cause of ment) criteria, a widely used classifica- striatocapsular SDIs in Asian patients, and tion scheme for ischemic stroke sub- it was reported14,15 that approximately half types, patients with traditional LS and of the patients with MCA stenosis also had ipsilateral intracranial stenosis are classi- SDIs. Owing to the high risk of stroke if fied as having “2 or more causes identi- occlusive lesions are present,10 the prog- From the Department of fied” and are lumped together with pa- nosis or recurrence rate in patients with Neurology, School of Medicine, tients with an “incomplete or negative LS and SDIs might depend on the exis- Ajou University, Suwon, evaluation” as having so-called ischemic tence of a parent arterial lesion. How- South Korea. stroke of unknown cause.9 ever, no long-term follow-up data on pa-

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NE 24 Excluded DWI 13 Had Subacute/Chronic Infarction 11 Had No Relevant Lesion on DWI

372 Randomized

136 Patients With Lacunar SD (LS) 236 Patients With Non-LS and SDIs on DWI and Larger Lesions on DWI

• Workup 34 Excluded 165 Excluded 4 Had a Cardioembolic Source Vascular, Cardiologic Laboratory 36 Had a Cardioembolic Source 4 Had Another Determined Cause 19 Had Undetermined Etiology • Follow-up 8 Had Incomplete Workup 41 Had No Determined Etiology 18 Were Lost to Follow-up mRS Barthel Index 13 Had Another Determined Etiology 19 Had Incomplete Workup 37 Were Lost to Follow-up

SAD Group PAD Group LAD Group n = 70 n = 32 n = 71

Figure 1. Selection and grouping of the patients. NE indicates neurologic examination; DWI, diffusion-weighted image; SDI, small deep infarct; SD, syndrome; LS, lacunar syndrome; mRS, modified Rankin Scale; SAD, small artery disease; PAD, parent arterial disease; LAD, large artery disease.

tients with occlusive lesions of the parent artery, such of prothrombic tendency, including protein C, protein S, an- as the MCA or the basilar artery (BA), are available. tithrombin III, and antiphospholipid antibodies (lupus anti- We hypothesized that the course of patients with coagulant and anticardiolipin IgG and IgM) were checked in lacunar stroke (with LS and SDIs on neuroimaging) all patients younger than 50 years. and an occlusive lesion of the parent artery is similar PATIENT SELECTION to that of large artery disease (LAD) rather than that of SAD. Therefore, we compared the long-term prognosis During the study, 396 consecutive patients with symptomatic of patients with LS and SDIs in terms of the stroke ischemic stroke were admitted to the Department of Neurol- recurrence rate, type of recurrent stroke, and progno- ogy at Ajou University Hospital (Figure 1). The group in- sis and its relation to possible clinical prognostic fac- cluded 136 patients with acute symptomatic lacunar infarcts. tors and the existence of a relevant large arterial Patients with acute symptomatic lacunar infarcts were defined lesion. Furthermore, we compared these patients with as those who were examined within a week of symptom onset those with non-LS. who showed focal neurologic deficits lasting longer than 24 hours that were consistent with LS and those who had rel- METHODS evant small deep lesions on DWI. All patients provided in- formed consent to participate in this study. Between December 1, 2000, and May 23, 2002, we prospec- Digital subtraction or magnetic resonance angiography, tively studied consecutive patients with ischemic stroke, who electrocardiography, and transthoracic echocardiography were had been examined within a week of symptom onset, and those performed in all patients, and transesophageal echocardiogra- who had a relevant lesion on diffusion-weighted imaging (DWI). phy and Holter monitoring were performed in selected patients, especially when the possibility of a cardioembolic source RISK FACTORS AND LABORATORY WORKUP was suggested or when no other cause of stroke was found. Pa- tients with potential sources of cardioembolism (atrial fibril- Patients were evaluated according to a protocol that included lation, mitral stenosis, prosthetic valve, myocardial infarction demographic data, medical history, vascular risk factors, and within 6 weeks, intracardiac clot, ventricular aneurysm, and the National Institutes of Health Stroke Scale at days 0 to 7.16 bacterial endocarditis)20 were excluded from the study (n=4) We used the same criteria for vascular risk factors as in our pre- because a stenotic lesion of an intracranial artery on digital sub- vious study17: hypertension, diabetes mellitus, hypercholester- traction or magnetic resonance angiography might represent a olemia, and smoking. On day 7 after hospital admission, all the partially recanalized clot rather than an atherosclerotic lesion. patients were evaluated according to the National Institutes of We also excluded (1) patients with other determined causes, Health Stroke Scale, the modified Rankin Scale,18 and the Bar- such as carotid dissection, hypercoagulable state, vasculitis, and thel Index.19 Laboratory tests included brain magnetic reso- complicated migraine (n=4); (2) those who did not undergo a nance imaging (1.5 T), vascular study, echocardiography, elec- complete workup (n=8); and (3) those who were not fol- trocardiography, and routine blood testing. Hemostatic markers lowed up for 1 year after the index stroke (n=18).

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©2004 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 3-month intervals for up to 12 months after stroke onset. Dur- Table 1. Clinical Characteristics of 173 Patients ing 1-year follow-up, information on the attainment of end points was obtained through direct clinical examination and through SAD Group PAD Group LAD Group information given by family members in cases of death (n=4). Characteristic (n = 70) (n = 32) (n = 71) Recurrent stroke was defined as a focal neurologic deficit oc- Age, mean ± SD, y 58 ± 12 60 ± 12 64 ± 13 curring suddenly in a vascular territory, lasting more than 24 Male sex, No. (%) 43 (61) 22 (69) 42 (59) hours, and occurring at any time after the acute phase of the 7,26 Territory, No. (%)* index stroke. The type of recurrent stroke was based on clini- Carotid 55 (79) 25 (78) 56 (79) cal and magnetic resonance imaging findings. To define the out- Vertebrobasilar 15 (21) 7 (22) 15 (21) come of patients with stroke, Barthel Index scores during fol- Lacunar syndrome, No. (%) low-up after the index stroke were divided into 2 classes at a Pure motor hemiplegia 45 (64) 24 (75) 0 cutoff value of 60, and the modified Rankin Scale scores were Sensory-motor stroke 12 (17) 6 (19) 0 divided at a cutoff value of 3.27 Pure sensory stroke 8 (11) 1 (3) 0 Dysarthria–clumsy hand 4 (6) 0 0 STATISTICAL ANALYSIS syndrome Ataxic-hemiparesis 1 (1) 1 (3) 0 Between-group differences were examined using the ␹2 test, Severity of stroke, Fisher exact test, unpaired t test, or 1-way analysis of vari- mean ± SD score† ance with post hoc analysis. Kaplan-Meier curves were used NIHSS on admission 2.5 ± 2.3 2.6 ± 2.5 6.6 ± 6.6 to estimate survival free of recurrent stroke or death. Poten- Barthel Index at 1 wk 93.5 ± 13.3 86.4 ± 26.0 63.8 ± 38.4 Risk factor, No. (%) tially significant predictors of poor prognosis and stroke-free Hypertension 45 (64) 17 (53) 43 (61) recurrence after acute symptomatic lacunar stroke (SAD or Diabetes mellitus 17 (24) 13 (41) 21 (30) PAD groups) were evaluated using multiple logistic regres- Smoking 33 (47) 15 (47) 30 (42) sion analysis. Initially, the 15 independent variables regard- Hypercholesterolemia 10 (14) 4 (13) 6 (8) ing the clinical and radiologic features were tested for their Stroke history 12 (17) 7 (22) 13 (18) individual associations with the outcome of interest. Those that were significant at the 0.2 level in the univariate model Abbreviations: LAD, large artery disease; NIHSS, National Institutes of Health were entered into the initial multivariate model. When the Stroke Scale; PAD, parent arterial disease; SAD, small artery disease. most parsimonious model was obtained by backward step- *Site of index infarcts on diffusion-weighted imaging. wise elimination of the nonsignificant factors, each excluded †The LAD group vs other subtypes, PϽ.001 on analysis of variance. variable was again entered into the model separately to test its contribution to the final model. Results are given as odds Based on their clinical syndrome, infarct size on DWI, and ratios as estimates of relative risk with a 95% confidence Ͻ the results of vascular studies, we divided the patients with acute interval. Statistical significance was established at P .05. symptomatic lacunar infarcts into 2 groups: (1) patients with LS and SDIs on DWI and no occlusive lesion of the relevant artery RESULTS (the SAD group) and (2) patients with LS and SDIs on DWI and an occlusive lesion of the parent artery occluding the deep per- GENERAL DATA forators (the PAD group). For comparison, patients with non- LS, a larger lesion on DWI, and an occlusive lesion of the rel- The study population consisted of 173 patients. There evant artery (the LAD group)9 were included; these lesions were intracranial (MCA, BA, and the intracranial portion of the in- were 107 men (62%) and 66 women (38%) (mean±SD ternal carotid artery or vertebral artery) or extracranial (carotid age, 62±10 years; age range, 37-85 years). According to sinus and extracranial portion of the vertebral artery). Lacunar the clinical, DWI, and angiographic findings, 70 pa- syndrome was defined as 1 of the 5 classic syndromes: pure mo- tients were classified in the SAD group, 32 in the PAD tor hemiplegia, pure sensory stroke, sensory-motor stroke, ataxic- group, and 71 in the LAD group. The patients’ clinical hemiparesis, and dysarthria–clumsy hand syndrome21,22; SDIs as characteristics are given in Table 1. subcortical or pontine hyperdense circular or oval lesions with The age, sex ratio, and territory of infarcts did not 23 a diameter of 15 mm or less on DWI ; and occlusive lesions as differ among the groups. The National Institutes of Health stenosis exceeding 50% or occlusion of the large intracranial ves- Stroke Scale score at hospital admission was signifi- sels and internal carotid artery according to the method of the cantly higher and the Barthel Index score 7 days after ad- Warfarin-Aspirin Symptomatic Intracranial Disease Study Group24 mission was significantly lower in the LAD group than and the North American Symptomatic Carotid Endarterectomy Ͻ Trial,25 respectively. Two of us (P.H.L. and U.S.J.), masked to in the other groups (P .001 for both). However, these the patient’s clinical presentation, interpreted the DWI and an- indices did not differ between the SAD and PAD groups. giographic features. Interobserver agreement was 91% for the pres- The risk factors for stroke and the types of LS did not ence of SDIs or larger infarcts and 85% for the presence of an differ between the SAD and PAD groups. Most patients occlusive lesion on angiography. were discharged from the hospital taking antiplatelet agents, and they showed good compliance (98%). PATIENT FOLLOW-UP Angiographic findings of the relevant and nonrelevant vessels are given in Table 2. The angiographic char- Hospital course was determined after 1 week and was defined acteristics of the patients in the PAD group included the as follows: improved, when the National Institutes of Health Stroke Scale score decreased 2 points or more; stable, when the presence of occlusive lesions of either the MCA or the BA, score decreased less than 2 points; worsening, when the score which were the parent arteries of the small perforators sup- increased after admission; and fluctuating, when the score in- plying the territory of the DWI lesion. Angiographic ste- creased and then decreased episodically or vice versa. Patients nosis of the relevant intracranial large artery (MCA or BA) were evaluated by one of us (O.Y.B.) at the outpatient clinic at was more prevalent in the PAD group (29 patients, 91%)

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©2004 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 Table 2. Distribution of Occlusive Lesions in 173 Patients Table 3. Recurrence Rate and Long-term Outcome by Angiography* SAD Group PAD Group LAD Group SAD Group PAD Group LAD Group Variable (n = 70) (n = 32) (n = 71) Site of Occlusive Lesions (n = 70) (n = 32) (n = 71) Hospital course, No. (%) Extracranial ICA 0/1 3/1 24/4 Stable course 65 (93) 28 (87) 49 (69) Intracranial ICA 0/2 1/0 4/3 Improved 23 12 20 Proximal portion of the MCA 0/1 22/2 28/5 Stable 42 16 29 Basilar artery 0/0 7/1 8/2 Unstable course 5 (7) 4 (13) 22 (31) Vertebral artery 0/0 0/0 7/1 Fluctuating 4 2 10 Overall 0/4 32/3 71/14 Worsening 1 2 12 Recurrence, No. (%)* 1 (1) 5 (16) 12 (17) Abbreviations: ICA, internal carotid artery; LAD, large artery disease; MCA, Time, mo middle cerebral artery; PAD, parent arterial disease; SAD, small artery Ͻ3127 disease. 3-6 0 1 2 *Data are given as number of patients with occlusive lesions on the 6-12 0 2 3 relevant/nonrelevant site. The nonrelevant site is the contralateral side or a Stroke syndrome different territory compared with the symptomatic lesion on Lacunar syndrome 1 3 2 diffusion-weighted imaging. Non–lacunar syndrome 0 2 10 Site of recurrent stroke† Same territory 1 5 11 Different territory 0 0 2 than in the LAD group (36 patients, 51%), whereas a ste- Long-term outcome notic lesion of the ipsilateral internal carotid artery (either Poor prognosis‡ 0 5 (16) 20 (28) extracranial or intracranial) or vertebral artery was more BI score, mean ± SD§ 98.4 ± 3.6 85.8 ± 26.9 71.8 ± 37.8 frequent in the LAD group (35 patients, 49%) than in the Deaths, No. (%) 0 2 (6) 7 (10) PAD group (4 patients, 13%). In the PAD group, the preva- Abbreviations: BI, Barthel Index; LAD, large artery disease; PAD, parent lence of stenotic lesions of the large intracranial artery (MCA arterial disease; SAD, small artery disease. or BA) was significantly higher at relevant sites than at non- *P = .001 by Fisher exact test. relevant sites (PϽ.001). †Compared with the site of index stroke. ‡Barthel Index score less than 60 or modified Rankin scale score greater than 3; P = .002 by Fisher exact test. HOSPITAL COURSE §BI score at 1-year follow-up, LAD vs PAD vs SAD group, PϽ.001 by analysis of variance. Unstable clinical courses (fluctuating or worsening) during the first 7 days of admission were significantly more common in the LAD group (22 patients, 31%) than in the other groups (P=.001). However, the frequency of such an unstable temporal profile was similar in the For patients with lacunar stroke (the SAD and PAD PAD (4 patients, 13%) and SAD (5 patients, 7%) groups groups), a multivariate logistic regression analysis of fac- (Table 3). tors obtained on hospital admission was performed, and the results showed that the presence of stenosis of the rel- RECURRENT STROKES evant artery was the only independent predictor of stroke recurrence in patients with LS and SDIs (odds ratio, 13.8; Figure 2 presents the Kaplan-Meier estimates of recur- 95% confidence interval, 1.5-123.9; P=.02). Other clini- rent stroke or death (Figure 2A) and recurrent stroke (Fig- cal and radiologic results, including epidemiologic data and ure 2B) for the different groups. During follow-up, 18 risk factors, the severity of neurologic deficits, the pres- patients (10%) had at least 1 recurrent stroke (Table 3); ence of stenosis of nonrelevant vessels, and the vascular recurrent strokes were hemorrhagic in 1 patient and is- territory involved, were not associated with an increased chemic in 17. The recurrence rate differed among the sub- risk of stroke recurrence (PϾ.05). types (P=.01). The recurrence rate in the PAD group (16%) was higher than that in the SAD group (1%; P=.01) PROGNOSIS 1 YEAR AFTER THE INDEX STROKE and similar to that in the LAD group (17%; P=.87). The type and site of recurrent stroke were correlated with those During the study, there were 9 deaths (5%): 3 were due of the index stroke. Five of the 32 patients in the PAD to different medical complications, such as upper gas- group had recurrent stroke: 3 of these 5 patients had an trointestinal tract bleeding or infection (2 in the LAD LS as their index stroke, and the recurrent stroke was in group and 1 in the PAD group); 1 patient each in the the same territory as the index stroke in all these pa- LAD and PAD groups had a myocardial infarction; and tients. These findings were similar to those for the LAD 4 patients in the LAD group had massive brain swelling. group: 12 recurrent strokes occurred in 71 patients in At the end of 1-year follow-up, the PAD group had the LAD group, most (10 patients, 83%) were non-LS in- more disable states than the SAD group (P=.002). None dex strokes, and new lesions were located in the same of the patients in the SAD group had a poor prognosis, vascular distribution as the index stroke in all but 1 pa- that is, Barthel Index scores less than 60 or modified tient. In the SAD group, 1 patient had recurrence of pure Rankin Scale scores greater than 3, compared with the motor hemiparesis in the same territory. LAD (20 patients, 28%) and PAD (5 patients, 16%) groups.

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©2004 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 ease in the pathogenesis of lacunar stroke is still contro- A 5,11,28-33 1.0 versial. Therefore, the presence of a cardiac or carotid embolic source and intracranial stenosis of the relevant artery in patients with lacunar stroke was thought to represent opportunistic disease or to be a marker of 0.8 diffuse atherosclerosis.28 Recently, no difference was found in the prevalence of ipsilateral and contralateral MCA disease in patients with LS or SDIs.28 However, our data

0.6 showed that a stenotic lesion of a large intracranial artery was more prevalent on the ipsilateral side than on the contralateral side in the PAD group, indicating a role

Survival of these stenotic lesions of large intracranial vessels in 0.4 the development of LS and SDIs on DWI. Such a difference might arise from the fact that intracranial atherosclerosis is more common in Asians than in Westerners, SAD Group 0.2 and it plays an important role in developing LS in Asians. PAD Group We found a high prevalence of intracranial stenosis of LAD Group the relevant artery in patients with lacunar stroke: 29 (28%) of 102 patients had stenosis of the relevant intra- 0.0 28 0 10 20 30 40 50 cranial artery, which is higher than in Westerners and 11,34 Weeks After Index Stroke similar to the rate in Chinese patients. Moreover, our 34 B findings, in agreement with published data, suggest that 1.0 parent arterial stenosis located adjacent to the orifice of perforators produces a small, deep, lacunalike infarct rather than a nonlacunar-type infarct; angiographic stenosis of the relevant intracranial large artery was more 0.8 prevalent in the PAD group, and extracranial large artery stenosis was more prevalent in the LAD group. Several studies1,6,7 have conducted long-term fol- 0.6 low-up of lacunar strokes and report mean annual stroke rates ranging from 4% to 7%. However, these studies did not use the same inclusion criteria, and stenosis of a large Survival intracranial artery was not considered in most of the stud- 0.4 ies. In the present study, the risk of stroke recurrence after lacunar stroke was 6% (6 of 102 patients with either PAD or SAD) during the first year after the index stroke, SAD Group 0.2 which was similar to that reported previously. Although PAD Group LAD Group stroke syndrome, SDIs on DWI, and a stable hospital course suggested lacunar stroke of benign course, our data showed a high frequency of recurrent stroke in patients with ste- 0.0 0 10 20 30 40 50 nosis of a large intracranial artery. These results, which Weeks After Index Stroke analyzed independent predictors of stroke recurrence after an index lacunar stroke, confirm this hypothesis. Ear- Figure 2. Kaplan-Meier curves showing survival without recurrent stroke or lier studies of serial angiography showed that lesion pro- death (A) and recurrent stroke (B). SAD indicates small artery disease; PAD, parent arterial disease; LAD, large artery disease. gression occurs frequently in patients with intracranial atherosclerosis (approximately 60%), particularly in me- dium-sized arteries (MCA or BA),35 and that the risk of COMMENT stroke is high if associated intracranial stenosis is present.10 Therefore, the detection of such occlusive lesions This study compared the recurrence and prognosis of in patients with lacunar strokes is of great importance in stroke patients with classic LS and the presence of SDIs clinical practice. Combined with the fact that patients with and an occlusive lesion of the relevant intracranial ar- LS and SDIs frequently had an associated occlusive lesion tery with those of SAD and LAD. To our knowledge, this of a large intracranial artery, and these patients had a higher is the first prospective study of a series of patients with rate of recurrence and poorer outcome, diagnostic and classic LS and the presence of an occlusive lesion of therapeutic approaches different from those for SAD, which the relevant large intracranial artery, evaluated accord- has a good prognosis, are needed. ing to a protocol that included DWI, echocardiog- Moreover, the high frequency of intracranial steno- raphy, and vascular studies, in which information sis in patients with LS and SDIs on DWI may also ex- on stroke recurrence and the prognosis at 1-year plain the difference in the type and location of recurrent follow-up were available. stroke observed in this study: the higher frequency of re- The role of potential cardioembolic sources, ca- current stroke with non-LS compared with others,4,5,7 oc- rotid artery disease, and intracranial atherosclerotic dis- curring more frequently in the same vascular distribu-

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©2004 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 tion of the index stroke compared with others,5,7 and being thy in patients with lacunar infarction: a prospective study. Stroke. 1988;19: associated with significantly increased disability com- 1093-1096. 7 9. Adams HP Jr, Bendixen BH, Kappelle LJ, et al. Classification of subtype of acute pared with others. In patients with SAD, the most im- ischemic stroke: definitions for use in a multicenter clinical trial: TOAST: Trial of portant vascular pathogenic mechanism seems to be wide- ORG 10172 in Acute Stroke Treatment. Stroke. 1993;24:35-41. spread intracranial SAD due to prolonged hypertension, 10. Bogousslavsky J, Barnett HJM, Fox AJ, Hachinski VC, Taylor W. Atherosclerotic whereas the propagation of thrombi at a preexisting in- disease of the middle cerebral artery. Stroke. 1986;17:1112-1120. tracranial stenosis may play an important role in recur- 11. Thajeb P. Large vessel disease in Chinese patients with capsular infarcts and prior ipsilateral transient ischemia. Neuroradiology. 1993;35:190-195. rent stroke in the PAD group. 12. Madden KP, Karanjia PN, Adams HP Jr, Carke WR, TOAST Investigators. Accu- In conclusion, although LS on examination, the pres- racy of initial stroke subtype diagnosis in the TOAST study. Neurology. 1995; ence of SDIs on neuroimaging, and a stable hospital course 45:1975-1979. suggest lacunar stroke of benign course, our follow-up 13. Bang OY, Heo JH, Kim JY, Park JH, Huh K. Middle cerebral artery stenosis is a data indicate that patients with PAD have an intracra- major clinical determinant in striatocapsular small, deep infarction. Arch Neu- rol. 2002;59:259-263. nial type of LAD. Owing to the high recurrence rate, phy- 14. Lyrer PA, Engelter S, Radu EW, Steck AJ. Cerebral infarcts related to isolated sicians dealing with patients with LS should be alert for middle cerebral artery stenosis. Stroke. 1997;28:1022-1027. large intracranial stenosis, especially in populations with 15. Wong KS, Huang YN, Gao S, Lam WW, Chan YL, Kay R. Intracranial stenosis in a higher frequency of intracranial stenosis. Further stud- Chinese patients with acute stroke. Neurology. 1998;50:812-813. ies with more patients and longer follow-up are needed. 16. Lyden P, Brott T, Tilley B, et al. Improved reliability of the NIH Stroke Scale using video training: the NINDS TPA Stroke Study Group. Stroke. 1994;25:2220- 2226. Accepted for publication November 19, 2003. 17. Bang OY, Lee PH, Joo SY, Lee JS, Joo IS, Huh K. Frequency and mechanisms of Author contributions: Study concept and design (Drs stroke recurrence after cryptogenic stroke. Ann Neurol. 2003;54:227-234. Bang, S. Y. Joo, and Huh); acquisition of data (Drs Bang, 18. van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJA, van Gijn J. Interob- S. Y. Joo, U. S. Joo, J. H. Lee, and I. S. Joo); analysis and server agreement for the assessment of handicap in stroke patients. Stroke. 1988; 19:604-607. interpretation of data (Drs Bang, S. Y. Joo, and P. H. Lee); 19. Mahoney FI, Barthel DW. Functional evaluation: the Barthel Index. Md State Med drafting of the manuscript (Drs Bang, S. Y. Joo, P. H. Lee, J. 1965;14:61-65. U. S. Joo, J. H. Lee, and I. S. Joo); critical revision of the 20. Kittner SJ, Sharkness CM, Price TR, et al. Infarcts with a cardiac source of em- manuscript for important intellectual content (Drs Bang and bolism in the NINCDS Stroke Data Bank: historical features. Neurology. 1990; Huh); statistical expertise (Drs Bang, P. H. Lee, and J. H. 40:281-284. 21. Fisher CM. Lacunar strokes and infarcts: a review. Neurology. 1982;32:871- Lee); administrative, technical, and material support (Drs 876. Bang, P. H. Lee, I. S. Joo, and Huh); study supervision (Drs 22. Fisher CM. Lacunar infarcts: a review. Cerebrovasc Dis. 1991;1:311-320. Bang and Huh). 23. 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