Asymptomatic Lacunar Infarcts Research Articles

Aberrant functional networks connectivity and structural atrophy in silent lacunar infarcts: relationship with cognitive impairments.

Silent or asymptomatic lacunar infarcts (LACI) are common in elderly individuals, but it remains largely unclear how these often neglected silent brain infarcts lead to multiple domain cognitive deficits and even Alzheimer's disease (AD). In this study, we investigated the difference between patients with silent LACI in basal ganglia region and healthy controls for the structural and functional changes in the aspects of alterations of gray matter (GM) volume and intra-/inter-default mode network (DMN) and salience network (SN) connectivity. Thirty patients with silent LACI in the basal ganglia region and thirty healthy controls participated in the study. Voxel-based morphometry analysis was employed to measure the GM volume. We further investigated the intra/inter-network connectivity of DMN and SN using resting-state functional magnetic resonance imaging. Compared with healthy controls, patients performed worse in cognitive function in the aspects of general mental status, attention, and memory. The LACIs showed more severe GM atrophy in insula, anterior cingulate cortex, caudate, and superior temporal pole than controls. The connectivity within and between two networks was also reduced in patients. Importantly, the disrupted connectivity correlated with the patients' cognitive performance. Our findings support the hypothesis that silent lacunar infarcts result in cognitive decline, GM, and functional connectivity loss.

Postprandial hypotension as a risk marker for asymptomatic lacunar infarction

Increasing blood pressure (BP) variability is reported to be a cardiovascular risk factor. However, the clinical implications of postprandial hypotension (PHYPO), a commonly observed BP variability in elderly persons, are poorly understood. Here, we investigated the possible associations between postprandial BP decline and asymptomatic cerebral damage in community residents. Study participants consisted of 1308 general community residents (65 ± 9 years old). Postprandial BP change was calculated from SBP measured just before and 30 min after lunch. PHYPO was defined as a decline in SBP of more than 20 mmHg. The presence of asymptomatic cerebrovascular damage was evaluated by brain MRI. Prevalence of lacunar infarction was significantly higher in participants with PHYPO (P = 0.004). A postprandial decline in SBP was linearly increased with the number of lacunar lesions (none, n = 1200, -3.4± 11.3 mmHg; one lesion, n = 82, -5.2 ± 11.8; two lesions, n = 18, -6.9 ± 11.5; three lesions, n = 7, -13.4 ± 11.3; and four lesions, n = 1, -27; P = 0.012). Although participants with PHYPO were older (P < 0.001) and had higher preprandial BP (P < 0.001) and faster pulse wave velocity (P = 0.001), multivariate analysis adjusted for these covariates indicated that postprandial BP decline was an independent determinant for the number of lacunar infarctions (P = 0.004). No significant associations were observed with grade of periventricular hyperintensity or frequency of microbleeds. These relationships were also found in an analysis based on central BP, whereas no superiority was seen in the analysis based on central BP. Postprandial BP decline is an overlooked risk marker for asymptomatic lacunar infarction in community residents.

Abstract T P360: Risk Factors Underlying Recurrent Subclinical Subcortical Cerebrovascular Lesions in Elderly Patients

Background and Purpose: Subclinical subcortical cerebrovascular lesions (SSCLs) are very common in elderly people. Accumulation of SSCLs may have additive or even synergic effects to the coexisting brain lesions such as Alzheimer’s pathology or symptomatic cerebrovascular lesions in elderly patients, but the mechanisms underlying the recurrence of SSCLs remains to be clarified. The present study was conducted to elucidate the contributing risk factors to the recurrent SSCLs. Subjects and Methods: The present study was based on 96 cases (55 men and 41women) with subcortical lesions, including 49 cases with symptomatic lacunar infarction, 36 cases with asymptomatic lacunar infarction, and 11 cases with symptomatic intracerebral hemorrhage. The mean age was 70.9 years. MRI studies were repeated with an average interval of 416 (248-822) days. Numbers of lacunar infarcts (LIs) and microbleeds (MBs) were counted in all MR slices, and the degree of white matter lesions (WMLs) was evaluated according the Fazekas’ categories, and those parameters were compared between the baseline and follow-up images. Laboratory studies included high sensitivity CRP (hsCRP), interleukin-6 (IL-6), serum lipid profile, glucose and brain natriuretic peptide (BNP). Results: The number of LIs increased in 16 cases whereas unchanged in 80 cases. The number of MBs increased in 16 cases, whereas unchanged in 80 cases. There was a deterioration in the degree of WMLs in 7 cases, whereas no change in 89 cases. Those with recurrent LIs had significantly greater number of LIs in the baseline MRI (p&lt;0.005), and those with recurrent MBs had greater numbers of LIs and MBs at baseline MRI (p&lt;0.005). Those who showed deterioration in WMLs had greater number of MBs and higher total cholesterol, LDL-cholesterol and lower HDL-cholesterol at baseline. Six cases showed combined recurrent vascular lesions, and had significantly elevated hsCRP and IL-6, and greater number of LIs and MB at baseline as compared with those with recurrence in single vascular lesions. Conclusion: The present result suggest that multiple subcortical vascular lesions are already a strong risk for the recurrence, and chronic inflammation may have additional risk for the combined vascular lesions.

Ambulatory Blood Pressure in Patients With Lacunar Stroke

Asymptomatic lacunar infarcts, white matter lesions, cerebral microbleeds, and enlarged perivascular spaces are MRI markers of cerebral small vessel disease (cSVD). Higher blood pressure (BP) levels are associated with the presence of these markers separately, but the association with the total burden of cSVD on brain MRI, expressed by the simultaneous presence of multiple markers of cSVD (a compound score), has not been investigated. We performed 24-hour ambulatory BP monitoring in 122 patients with first-ever lacunar stroke. On brain MRI, we scored the presence of each marker of cSVD. One point was awarded for the presence of each marker, producing a score between 0 and 4. Associations with BP levels were tested with ordinal regression analyses. Eighteen (15%) patients had no markers of cSVD, and 6 (5%) patients had 4 markers. Most patients (45; 37%) had 2 different markers. After correction for age and sex, higher 24-hour, day, and night systolic (24-hour odds ratio, 1.25; 95% confidence interval, 1.02-1.52 per 10 mm Hg) and diastolic (24-hour odds ratio, 1.32; 95% confidence interval, 1.12-1.56 per 5 mm Hg) BP were all significantly associated with an increasing total burden of cSVD. We found a positive association of ambulatory BP levels with total burden of cSVD on brain MRI. With increasing BP levels, there is a piling up of damage in the brain. We suggest that further cSVD studies also consider viewing the total burden in addition to each of the MRI markers separately.

Accumulation of MRI Markers of Cerebral Small Vessel Disease is Associated with Decreased Cognitive Function. A Study in First-Ever Lacunar Stroke and Hypertensive Patients

Background: White matter lesions (WMLs), asymptomatic lacunar infarcts, brain microbleeds (BMBs), and enlarged perivascular spaces (EPVS) have been identified as silent lesions due to cerebral small vessel disease (cSVD). All these markers have been individually linked to cognitive functioning, but are also strongly correlated with each other. The combined effect of these markers on cognitive function has never been studied and would possibly provide more useful information on the effect on cognitive function.Methods: Brain MRI and extensive neuropsychological assessment were performed in 189 patients at risk for cSVD (112 hypertensive patients and 77 first-ever lacunar stroke patients). We rated the presence of any asymptomatic lacunar infarct, extensive WMLs, any deep BMB, and moderate to extensive EPVS in the basal ganglia. The presence of each marker was summed to an ordinal score between 0 and 4. Associations with domains of cognitive function (memory, executive function, information processing speed, and overall cognition) were analyzed with correlation analyses.Results: Correlation analyses revealed significant associations between accumulating cSVD burden and decreased performance on all cognitive domains (all p ≤ 0.001). Results remained significant for information processing speed (r = −0.181, p = 0.013) and overall cognition (r = −0.178, p = 0.017), after correction for age and sex. Testing of trend using linear regression analyses revealed the same results.Discussion: We tested a new approach to capture total brain damage resulting from cSVD and found that accumulation of MRI burden of cSVD is associated with decreased performance on tests of information processing speed and overall cognition, implying that accumulating brain damage is accompanied by worse cognitive functioning.

Higher ambulatory blood pressure relates to enlarged Virchow-Robin spaces in first-ever lacunar stroke patients

Enlarged Virchow-Robin spaces (EVRS) are considered to be a sign of cerebral small vessel disease. Hypertension is an important risk factor for cerebral small vessel disease, whereas ambulatory blood pressure (BP) is the strongest predictor of hypertension-related brain damage. However, the association between ambulatory BP levels and EVRS has never been investigated. The aim of this study was to determine the association between ambulatory BP levels and EVRS. In 143 first-ever lacunar stroke patients, we performed 24-h ambulatory BP monitoring after the acute stroke phase. On brain MRI we counted EVRS in the basal ganglia and the centrum semiovale. We graded the number of EVRS at each level into a three-category severity scale. We assessed the association between BP levels and EVRS by ordinal regression analysis. After adjusting for age, sex, extensive white matter lesions, and asymptomatic lacunar infarcts, higher day systolic (OR 1.21; 95 % CI 1.00–1.46 per 10 mmHg), day diastolic (1.18; 95 % CI 1.02–1.37 per 5 mmHg) and 24-h diastolic (OR 1.18; 95 % CI 1.01–1.37 per 5 mmHg) ambulatory BP levels were associated with EVRS at the basal ganglia level. No relation was found between ambulatory BP levels and EVRS in the centrum semiovale. Higher day ambulatory BP levels are associated with EVRS in the basal ganglia. This association was independent of the presence of extensive white matter lesions and asymptomatic lacunar infarcts. Our results imply that basal ganglia EVRS should be regarded as a separate manifestation of BP-related brain damage.

Angiogenic T-Cells and Putative Endothelial Progenitor Cells in Hypertension-Related Cerebral Small Vessel Disease

Cerebral small vessel disease (CSVD) may be caused by endothelial dysfunction, whereas endothelial progenitor cells (EPC) may attenuate endothelial dysfunction. Their vitality is lower in CSVD. A subset of lymphocytes, angiogenic T-cells, is capable to stimulate EPC function. The purpose of our study was to explore the relation between CSVD manifestations, angiogenic T-cells, and EPC in hypertensive patients with CSVD. We compared 32 essential hypertensive patients with CSVD (white matter lesions, asymptomatic lacunar infarcts, or microbleeds on 1.5-Tesla MRI) to 29 age-matched and sex-matched hypertensive controls. We counted angiogenic T-cells (CD3(+)/CD31(+)/CD184(+)) and putative EPC (CD31(+)/CD34(+)/CD45(-)/KDR(+)) by flow cytometry and determined EPC vitality by in vitro cluster formation. Putative EPC numbers were lower in hypertensive individuals with CSVD than in those without (10±7(.)10(3)/mL versus 13±6(.)10(3)/mL [median±interquartile range]; P=0.011). Angiogenic T-cell numbers were also lower in hypertensive individuals with CSVD than in those without (0.56±0.25(.)10(9)/mL versus 0.78±0.50(.)10(9)/mL; P=0.008). Higher angiogenic T-cell numbers independently related to absence of CSVD (odds ratio, 0.088; 95% confidence interval, 0.012-0.627). Our data suggest that angiogenic T-cells and putative EPC independently relate to radiological CSVD manifestations in hypertensive patients.

Family History of Stroke Is an Independent Risk Factor for Lacunar Stroke Subtype With Asymptomatic Lacunar Infarcts at Younger Ages

Results from case-control and case-case studies indicate that a positive family history of stroke (FHstroke) is an independent risk factor for lacunar stroke. Different lacunar stroke phenotypes can be distinguished on the basis of the presence of asymptomatic lacunar infarcts (aLACs), ischemic white-matter lesions, or brain microbleeds. The aim of the present study was to determine whether familial aggregation of stroke was different for lacunar stroke phenotypes. In 157 patients with a first-ever lacunar stroke, a complete first-degree FHstroke was obtained by a standardized questionnaire and additional interview. Lacunar stroke patients were categorized successively into groups, depending on the presence of aLACs, ischemic white-matter lesions, and brain microbleeds on magnetic resonance imaging. Fifty-two percent of patients reported a positive FHstroke in at least one of their first-degree relatives. In younger (<65 years) probands, a high frequency of parental FHstroke (59% versus 20%, P<0.01) in those with aLACs compared with probands without aLACs was found. In multivariate analysis, the strongest associations were found for parental FHstroke (odds ratio=6.46; 95% CI=1.96 to 21.33), maternal FHstroke (odds ratio=4.00; 95% CI=1.18 to 13.56), and paternal FHstroke (odds ratio=5.40; 95% CI=1.14 to 25.61). A family history of stroke might be an independent risk factor for the lacunar stroke phenotype with aLACs at younger ages, suggesting a role for genetic factors in this phenotype caused by diffuse vasculopathy.

Endothelial Activation in Lacunar Stroke Subtypes

Lacunar stroke (LS) can be subtyped according to the absence (isolated lacunar infarct [ILA]) or presence of concomitant white matter lesions (WML) and/or asymptomatic lacunar infarcts. Endothelial activation is thought to play a pivotal role in the subtype with WML and/or asymptomatic lacunar infarcts. The aim of this study was to evaluate whether endothelial activation is associated with WML and/or asymptomatic lacunar infarcts in LS patients. Here, we determined levels of circulating blood markers of endothelial function in LS patients. In 149 patients, all of whom had brain-MRI, levels of tissue plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1), tPA-PAI-1 complex, von Willebrand factor, tissue factor, thrombomodulin, and coagulation factor VIII were determined. Levels of blood markers were related to subtypes of LS and adjusted for age, gender, and vascular risk factors. In subtypes of LS, tPA activity was increased in patients with WML (0.79 IU/mL vs 0.44 IU/mL for ILA; P=0.02) and PAI-1-antigen levels were lowest in patients with WML (27.5 ng/mL vs 44.0 ng/mL for ILA; P=0.02). The association between WML and PAI-1 remained significant after multivariable analysis (OR, 0.99; 95% CI, 0.98-1.00 per ng/mL change of PAI-1; P=0.04). We found further evidence for the hypothesis of endothelial activation in the subtype of LS caused by a diffuse small vessel vasculopathy, as we found higher levels of tPA in patients with concomitant extensive WML than in those with ILA. Second, low levels of PAI-1 were associated with WML. We postulate that differences in activity of components of the fibrinolytic system might contribute to WML development.

Brain Microbleeds Relate to Higher Ambulatory Blood Pressure Levels in First-Ever Lacunar Stroke Patients

Hypertension is an important risk factor for brain microbleeds (BMBs) in lacunar stroke patients. However, beyond the qualitative label "hypertension," little is known about the association with ambulatory blood pressure (BP) levels. In 123 first-ever lacunar stroke patients we performed 24-hour ambulatory BP monitoring after the acute stroke-phase. We counted BMBs on T2*-weighted gradient-echo MR images. Because a different etiology for BMBs according to location has been suggested, we distinguished between BMBs in deep and lobar location. BMBs were seen in 36 (29.3%) patients. After adjusting for age, sex, number of antihypertensive drugs, asymptomatic lacunar infarcts, and white matter lesions, we found 24-hour, day, and night systolic and diastolic BP levels to be significantly associated with the presence and number of BMBs (odds ratios 1.6 to 2.3 per standard deviation increase in BP). Distinguishing between different locations, various BP characteristics were significantly associated with the presence of deep (or combined deep and lobar) BMBs, but not with purely lobar BMBs. Our results underline the role of a high 24-hour BP load as an important risk factor for BMBs. The association of BP levels with deep but not purely lobar BMBs is in line with the idea that different vasculopathies might be involved. Deep BMBs may be a particular marker of BP-related small vessel disease, but longitudinal and larger studies are now warranted to substantiate these findings.

Cerebral small vessel disease and chronic kidney disease (CKD): Results of a cross-sectional study in community-based Japanese elderly

Chronic kidney disease (CKD) is known as a risk factor for cardiovascular disease. In recent years, several experimental and epidemiological studies have suggested that CKD is associated with endothelial dysfunction; thereby, a CKD state may initiate both large and small vessel damage. The association between renal dysfunction and asymptomatic lacunar infarction was reported in a hospital-based study, whereas the relationship between cerebral small vessel disease (SVD)-related lesions and CKD could not be clarified in a community-based study. We performed a cross-sectional study to determine the relationship between silent cerebral SVD-related lesions and CKD in a total of 625 community-based Japanese elderly. In this study, subjects with lower estimated glomerular filtration rate levels tended to have more lacunar infarcts and higher grades of white matter lesions (WMLs). In addition, the mean grades of WMLs or the mean numbers of lacunar infarction in the subjects with albuminuria were greater than those in subjects without albuminuria. In the logistic regression analysis, the association between the presence of CKD and lacunar infarction or moderate WMLs (Fazekas grades 2 and 3) was statistically significant (odds ratio [OR]: 1.86 and 1.50, respectively). Furthermore, as we performed additional analysis, excluding the subjects with stage 2 hypertension (those with casual blood pressure >or=160/100 mm Hg) or diabetes, CKD remained to be an independent risk for cerebral SVD-related lesions. This is the first study showing the relationship between silent SVD-related brain lesions and the presence of CKD, independently of conventional cardiovascular risk factors, in community-based elderly.

Virchow-Robin spaces relate to cerebral small vessel disease severity

Virchow-Robin spaces (VRs) are perivascular spaces surrounding the deep perforating brain arteries. VRs dilatation is pathologic, and it could be a manifestation of cerebral small vessel disease. In the present study we assessed the relation between VRs and silent ischemic lesions in a cohort of patients with cerebral small vessel disease. We divided dilated VRs on MRI (1.5 Tesla) into three semi-quantitative categories in 165 first ever lacunar stroke patients. We counted asymptomatic lacunar infarcts and graded white matter lesions, and compared the prevalence of vascular risk factors in different categories of VRs. We also determined independent predictors of silent ischemic lesions. VRs at basal ganglia level related to age, hypertension, asymptomatic lacunar infarcts, and white matter lesions. VRs at basal ganglia level predicted silent ischemic lesions (odds ratio 10.58 per higher VRs category; 95 %- confidence interval 3.40 - 32.92). Dilated VRs in the basal ganglia relate to the severity of cerebral small vessel disease and might be a manifestation of the same small vessel abnormality that causes silent ischemic lesions. This adds a role for VRs as a potential marker for small vessel disease.

Computer-Aided Diagnosis Scheme for Detection of Lacunar Infarcts on MR Images

The detection and management of asymptomatic lacunar infarcts on magnetic resonance (MR) images are important tasks for radiologists to ensure the prevention of severe cerebral infarctions. However, accurate identification of the lacunar infarcts on MR images is a difficult task for the radiologists. Therefore the purpose of this study was to develop a computer-aided diagnosis scheme for the detection of lacunar infarcts to assist radiologists' interpretation as a "second opinion." Our database comprised 1,143 T1- and 1,143 T2-weighted images obtained from 132 patients. The locations of the lacunar infarcts were determined by experienced neuroradiologists. We first segmented the cerebral region in a T1-weighted image by using a region growing technique for restricting the search area of lacunar infarcts. For identifying the initial lacunar infarcts candidates, a top-hat transform and multiple-phase binarization were then applied to the T2-weighted image within the segmented cerebral region. For eliminating the false positives (FPs), we determined 12 features--the locations x and y, signal intensity differences in the T1- and T2-weighted images, nodular components from a scale of 1 to 4, and nodular and linear components from a scale of 1 to 4. The nodular components and the linear components were obtained using a filter bank technique. The rule-based schemes and a support vector machine with 12 features were applied to the regions of the initial candidates for distinguishing between lacunar infarcts and FPs. Our computerized scheme was evaluated by using a holdout method. The sensitivity of the detection of lacunar infarcts was 96.8% (90/93) with 0.76 FP per image. Our computerized scheme would be useful in assisting radiologists for identifying lacunar infarcts in MR images.

Atherosclerotic changes in intracranial and extracranial large arteries in apparently healthy persons with asymptomatic lacunar infarction

To clarify the relationship between large-vessel disease and asymptomatic cerebral infarction (ACI), we evaluated atherosclerotic changes in intracranial and extracranial arteries in adults with and without ACI. Subjects were 142 apparently healthy persons with ACI on magnetic resonance imaging (MRI) (ACI group) and 605 age matched persons without cerebral infarction on MRI. The 605 age-matched persons were divided into 380 persons with cerebrovascular risk factors (RF group) and 225 persons without cerebrovascular risk factors (NC group). Intracranial arteries (internal carotid artery, main trunks of the middle cerebral artery, and basilar artery) were examined by magnetic resonance angiography (MRA), and extracranial carotid arteries were investigated using B-mode ultrasonography. Stenosis of 25% to 49% in intracranial arteries detected on MRA was significantly more frequent in the ACI group (16%) than in the RF group (8%) or NC group (4%) (P < .05 and P < .001, respectively). On B mode ultrasonography, the prevalences of <25% stenosis (29%) and 25% to 49% stenosis (7%) in extracranial carotid arteries in the ACI group were significantly greater than those in the NC group (16% and 2% respectively, P < .05), whereas >/=50% stenosis was significantly more frequent in the ACI group (6%) than in the RF group (2%; P < .05). There was no statistically significant difference in prevalence of stenosis in intracranial and extracranial large arteries between persons with ipsilateral stenosis and infarction and persons with contralateral stenosis and infarction. We conclude that potential major cerebral vessel disease frequently coexists in persons with asymptomatic lacunar infarction.

Commentary on Professor Hobson’s first-person account of a lateral medullary stroke (CVA): Affirmative action for the brainstem in consciousness studies?

Periodic limb movements (PLMs) can increase the risk of cardiovascular disease and mortality. Small vessel disease (SVD) has been considered a precursor to symptomatic stroke. We aimed to investigate the association between PLMs and cerebral SVD.We enrolled participants who visited our clinic for the evaluation of sleep disturbance and underwent overnight polysomnography and brain magnetic resonance imaging. The processing steps included rating and analyzing white matter hyperintensities (WMHs), cerebral microbleeds (CMBs), asymptomatic lacunar infarctions (ALIs), perivascular spaces (PVSs), and calculating the total SVD score. Logistic regression and correlation analyses were used to examine the association between PLMs during sleep (PLMS) and SVD.A total of 31 (19 men and 12 women) patients with PLMS index ≥ 15/h were enrolled. The mean age was 61.7 years and the median PLMS index was 46.5/h. A total of 29 controls (16 men and 13 women) with PLMS index < 5/h were also included. PLMS index was positively associated with an increase in WMHs, ALIs, and PVSs (odds ratio [OR] = 1.022, 95% confidence interval [CI] = 1.003–1.040, p = 0.008; OR = 1.024, 95% CI = 1.006–1.043, p = 0.010; OR = 1.029, 95% CI = 1.010–1.049, p = 0.003, respectively). Correlation analyses revealed that total SVD score was significantly correlated with PLMS index (r = 0.504, p < 0.001).An elevated PLMS index was associated with an increase in WMHs, ALIs, PVSs, and total SVD burden. Our study suggests that PLMS is a marker for SVD, which carries a potential risk for progression to overt stroke or cognitive impairment.

Two types of lacunar infarcts: further arguments from a study on prognosis.

Earlier, we found that lacunar stroke patients with > or =1 asymptomatic lacunar infarcts on CT had leukoaraiosis and hypertension significantly more often than patients without such lesions, and we hypothesized that 2 types of small-vessel disease could be distinguished during life: arteriolosclerosis and microatheromatosis, respectively. Differences in prognosis might sustain this hypothesis of 2 lacunar stroke entities. Therefore, we performed a follow-up in 333 patients with first lacunar stroke, distinguishing those with > or =1 asymptomatic lacunar lesions (LACI+) from those without such lesions (LACI-). Cross-sectional follow-up was performed after 785+/-479 days (mean+/-SD) in 104 LACI+ patients and 865+/-545 days in 229 LACI- patients. Mortality at the end of follow-up was 33% in LACI+ and 21% in LACI- patients [odds ratio (OR), 1.74; 95% confidence interval (CI), 1.01 to 3.01]. Stroke recurrence rate was 21% in LACI+ and 11% in LACI- (OR, 2.09; 95% CI, 1.08 to 4.06). Forty percent of LACI+ and 26% of LACI- patients had unfavorable outcome at the end of follow-up (OR, 1.95; 95% CI, 1.17 to 3.26). Kaplan-Meier curves showed less favorable survival in LACI+ (log-rank test, P=0.0218) and survival free of stroke (log-rank test, P=0.0121) than in LACI-. When we restricted the analysis to patients with both silent lesions and leukoaraiosis (n=63) compared with those without (n=196), differences were even more pronounced. Prognosis for mortality, recurrent stroke, and overall functional outcome in lacunar stroke patients with > or =1 silent lacunar lesions is more unfavorable than in patients without such lesions. These findings sustain the idea of 2 lacunar stroke entities.

Associations of plasma endothelin concentration with carotid atherosclerosis and asymptomatic cerebrovascular lesions in patients with essential hypertension.

We studied the association of endothelin (ET)-1 with carotid atherosclerosis and asymptomatic cerebrovascular lesions in patients with essential hypertension. Neurologically normal patients with essential hypertension (n=293; 138 male, 155 female; mean age, 65 years) and age-matched control subjects (n=242) were studied with B-mode ultrasonography of the common and internal carotid arteries and magnetic resonance imaging of the brain. Plasma ET-1 was measured by enzyme immunoassay. Hypertensive patients were divided into groups with carotid plaques and low ET-1 concentrations (< 0.75 pg/ml; PL group); carotid plaques and mid-range ET-1 (0.75 to 1.55 pg/ml; PM group); carotid plaques and high ET-1 (> or = 1.55 pg/ml; PH group); no plaques and low ET-1 (NPL); no plaques and mid-range ET-1 (NPM); and no plaques and high ET-1 (NPH). Overall, ET-1 concentrations were significantly higher in patients than in control subjects. Carotid plaque prevalence was significantly related to ET-1 in hypertensive patients. ET-1 showed a significant positive relationship with the number of asymptomatic lacunar infarcts of the brain in hypertensive patients with carotid plaques (rho=0.48, p<0.001). No significant relationship was seen between ET-1 and periventricular hyperintensity scores in patients with plaques. ET-1 did not show a relationship to either brain lesion type in patients without carotid plaques. Thus, ET-1 may foster asymptomatic lacunar cerebral infarcts by promoting carotid atherosclerosis in patients with essential hypertension.

Difference in Glucose Metabolism Between Persons with Asymptomatic Lacunar Infarction and Persons Demonstrating Incidental MRI Hyperintensities but not Infarction

Difference in Glucose Metabolism Between Persons with Asymptomatic Lacunar Infarction and Persons Demonstrating Incidental MRI Hyperintensities but not Infarction

American Heart Association Prevention Conference. IV. Prevention and Rehabilitation of Stroke. Etiology of stroke.

The diagnosis of arterial stroke differentiates ischemia from hemorrhage. The former may be due to arterial occlusion or stenosis, the latter to leakage or rupture of an artery. Computed tomography (CT) and magnetic resonance imaging (MRI) have shown that this basic differentiation cannot be reliably made from the history and clinical examination alone. Of the clinical stroke syndromes, only Wallenberg’s syndrome has not been reported to be due to hemorrhage. When CT or MRI is not available for diagnosis, spinal tap is reliably positive only when the aneurysm or arteriovenous malformation has ruptured into the subarachnoid space; the results are often normal when a small hemorrhage occurs in the parenchyma. For some therapies, notably neuroprotective agents, the potential benefits for ischemia do not seem to be offset by potential harm in the case of hemorrhage. However, because fibrinolytics, antithrombotic agents, or surgery are treatment options, diagnostic certainty is essential to avoid harming the patient. Most—but not all—strokes have a sudden or rapidly evolving onset. Differential diagnosis of sudden change in focal neurological status includes seizures or postepileptic paralysis, hemorrhage into a tumor (itself a form of stroke), and migraine. Neuroimaging helps to differentiate between these and the cause of short-lived symptoms (transient ischemic attack [TIA]) usually presumed due to ischemia but possibly due to new-onset infarction or hemorrhage. More precise classification of stroke into a pathogenic subtype (embolism, thrombosis, decreased perfusion or “lacunar” infarction, leakage, or rupture) evades the best clinical skills. The classification of stroke mechanism depends on the presence of risk factors for stroke (preexisting condition or circumstance epidemiologically related to stroke) and etiologies (disease directly causing the mechanism) that implicate the cause of stroke in a given patient. However, more than one risk factor and etiology are frequently present in the same patient and may be related …

Two clinically distinct lacunar infarct entities? A hypothesis.

We investigated the hypothesis that patients with one or more asymptomatic lacunar infarcts and those with only one symptomatic lacunar infarct represent two clinically distinct lacunar infarct entities. In a prospective series of 100 lacunar infarct patients, univariate and multivariate logistic regression analysis was performed on clinical features, vascular risk factors, and leukoaraiosis between patients with and without asymptomatic lacunar infarcts. Patients with asymptomatic lacunar infarcts had hypertension significantly more often (71% versus 43%; [crude] odds ratio, 3.31; 95% confidence intervals, 1.16-9.43; p < 0.05) and had leukoaraiosis significantly more often (71% versus 19%; [crude] odds ratio, 10.67; 95% confidence intervals, 3.81-32.10; p < 0.001) than those with only a symptomatic lacunar infarct. After multivariate logistic regression analysis, only leukoaraiosis was significantly associated with the presence of asymptomatic lacunar infarcts. The asymptomatic lacunar infarcts differed in location, involved vascular territory, and volume from the symptomatic infarcts. Two distinct lacunar infarct entities might be broadly distinguished during life: lacunar infarct patients with a single, symptomatic lacunar infarct, and patients with multiple lacunar infarcts and a high frequency of hypertension and leukoaraiosis, in which the underlying small-vessel vasculopathy might be different.