Changes in intra- and extracranial carotid plaque calcification: a 2-year follow-up study.

Extra- and intracranial carotid plaque calcification might have plaque-stabilizing effects, yet information on changes in plaque calcification remains scarce. We evaluated changes in carotid plaque calcification over 2 years follow-up in patients with symptomatic carotid artery disease. This study is based on the PARISK-study, a multicenter cohort study, with TIA/minor stroke patients with ipsilateral mild-to-moderate carotid artery stenosis (< 70%). We included 79 patients (25% female, mean age 66 years) who underwent CTA imaging with 2 year interval. We assessed the volume of extra- and intracranial carotid artery calcification (ECAC and ICAC) and calculated the difference between baseline and follow-up ECAC and ICAC volume. We performed multivariable regression analyses to investigate the association between change of ECAC or ICAC with cardiovascular determinants. ECAC. We found increase (46.2%) and decrease (34%) in ECAC volume during 2 year follow-up, both significantly correlation with baseline ECAC volume (OR = 0.72, 95% CI 0.58-0.90 respectively OR = 2.24, 95% CI 1.60-3.13).We found significant correlation for change in ECAC volume with diabetes (ß = 0.46, 95% CI 0.03-0.89) and baseline ECAC volume (ß = 0.81, 95% CI 0.73-0.88). ICAC. We found increase (45.0%) and decrease (25.0%) in ICAC volume. The ICAC decrease was significantly correlated with baseline ICAC volume (OR = 2.17, 95% CI 1.48-3.16), age (OR = 2.00, 95% CI 1.19-3.38) and use of antihypertensive drugs (OR = 3.79, 95% CI 1.20-11.96]).The overall change of ICAC volume was also significantly correlated with diabetes (ß = 0.92, 95% CI 1.59-7.02), use of oral hypoglycemic drugs (ß = 0.86, 95% CI 0.12-1.59) and baseline ICAC volume (ß = 0.71, 95% CI 0.55-0.87). We provide novel insights into the dynamics of carotid plaque calcification in symptomatic stroke patients.

The course of post-stroke apathy in relation to cognitive functioning: a prospective longitudinal cohort study.

Apathy is common after stroke and has been associated with cognitive impairment. However, causality between post-stroke apathy and cognitive impairment remains unclear. We assessed the course of apathy in relation to changes in cognitive functioning in stroke survivors. Using the Apathy Scale (AS) and cognitive tests on memory, processing speed and executive functioning at six- and 15 months post-stroke we tested for associations between (1) AS-scores and (change in) cognitive scores; (2) apathy course (persistent/incident/resolved) and cognitive change scores. Of 117 included participants, 29% had persistent apathy, 13% apathy resolving over time and 10% apathy emerging between 6-15 months post-stroke. Higher AS-scores were cross-sectionally and longitudinally associated with lower cognitive scores. Relations between apathy and cognitive change scores were ambiguous. These inconsistent relations between apathy and changes in cognition over time suggest that post-stroke apathy does not directly impact cognitive performance. Both these sequelae of stroke require separate attention.

Proximal Region of Carotid Atherosclerotic Plaque Shows More Intraplaque Hemorrhage: The Plaque at Risk Study.

BACKGROUND AND PURPOSE: Intraplaque hemorrhage contributes to lipid core enlargement and plaque progression, leading to plaque destabilization and stroke. The mechanisms that contribute to the development of intraplaque hemorrhage are not completely understood. A higher incidence of intraplaque hemorrhage and thin/ruptured fibrous cap (upstream of the maximum stenosis in patients with severe [≥70%] carotid stenosis) has been reported. We aimed to noninvasively study the distribution of intraplaque hemorrhage and a thin/ruptured fibrous cap in patients with mild-to-moderate carotid stenosis. MATERIALS AND METHODS: Eighty-eight symptomatic patients with stroke (<70% carotid stenosis included in the Plaque at Risk study) demonstrated intraplaque hemorrhage on MR imaging in the carotid artery plaque ipsilateral to the side of TIA/stroke. The intraplaque hemorrhage area percentage was calculated. A thin/ruptured fibrous cap was scored by comparing pre- and postcontrast black-blood TSE images. Differences in mean intraplaque hemorrhage percentages between the proximal and distal regions were compared using a paired-samples t test. The McNemar test was used to reveal differences in proportions of a thin/ruptured fibrous cap. RESULTS: We found significantly larger areas of intraplaque hemorrhage in the proximal part of the plaque at 2, 4, and 6 mm from the maximal luminal narrowing, respectively: 14.4% versus 9.6% (P = .04), 14.7% versus 5.4% (P < .001), and 11.1% versus 2.2% (P = .001). Additionally, we found an increased proximal prevalence of a thin/ruptured fibrous cap on MR imaging at 2, 4, 6, and 8 mm from the MR imaging section with the maximal luminal narrowing, respectively: 33.7% versus 18.1%, P = .007; 36.1% versus 7.2%, P < .001; 33.7% versus 2.4%, P = .001; and 30.1% versus 3.6%, P = .022. CONCLUSIONS: We demonstrated that intraplaque hemorrhage and a thin/ruptured fibrous cap are more prevalent on the proximal side of the plaque compared with the distal side in patients with mild-to-moderate carotid stenosis.

Presentation outside office hours does not negatively influence treatment times for reperfusion therapy for acute ischemic stroke.

BACKGROUND: Treatment outside office hours has been associated with increased workflow times for intravenous thrombolysis (IVT) in acute ischemic stroke (AIS). Limited data suggest that this "off-hours effect" also exists for endovascular treatment (EVT). We investigated this phenomenon in a well-organized acute stroke care region in the Netherlands. METHODS: Retrospective, observational cohort study of consecutive patients with AIS who received reperfusion therapy in the Greater Amsterdam Area, consisting of 14 primary stroke centers and 1 comprehensive stroke center (IVT: 2009-2015, EVT: 2014-2017). Office hours were defined as presentation during weekdays between 8 AM and 5 PM, excluding National Festive days. Primary outcome was door-to-treatment time (door-to-needle [DNT] for IVT, door-to-groin [DGT] for EVT). For DGT, we used the door time of the first hospital. Other outcomes were in-hospital mortality, modified Rankin Scale (mRS) score at 90 days and symptomatic intracranial hemorrhage (sICH). We performed multivariable linear and logistic regression analyses and used multiple imputation to account for missing values. RESULTS: In total, 59% (2450/4161) and 61% (239/395) of patients treated with IVT and EVT, respectively, presented outside office hours. Median DNT was minimally longer outside office hours (32 vs. 30 min, p = 0.024, adjusted difference 2.5 min, 95% CI 0.7-4.2). Presentation outside office hours was not associated with a longer DGT (median 130 min for both groups, adjusted difference 7.0 min, 95% CI - 4.2 to 18.1). Clinical outcome and sICH rate also did not differ. CONCLUSION: Presentation outside office hours did not lead to clinically relevant treatment delays for reperfusion therapy in patients with AIS.

Plaque Composition as a Predictor of Plaque Ulceration in Carotid Artery Atherosclerosis: The Plaque At RISK Study.

BACKGROUND AND PURPOSE: Plaque ulceration is a marker of previous plaque rupture. We studied the association between atherosclerotic plaque composition at baseline and plaque ulceration at baseline and follow-up. MATERIALS AND METHODS: We included symptomatic patients with a carotid stenosis of <70% who underwent MDCTA and MR imaging at baseline (n = 180). MDCTA was repeated at 2 years (n = 73). We assessed the presence of ulceration using MDCTA. Baseline MR imaging was used to assess the vessel wall volume and the presence and volume of plaque components (intraplaque hemorrhage, lipid-rich necrotic core, and calcifications) and the fibrous cap status. Associations at baseline were evaluated with binary logistic regression and reported with an OR and its 95% CI. Simple statistical testing was performed in the follow-up analysis. RESULTS: At baseline, the prevalence of plaque ulceration was 27% (49/180). Increased wall volume (OR = 12.1; 95% CI, 3.5-42.0), higher relative lipid-rich necrotic core (OR = 1.7; 95% CI, 1.3-2.2), higher relative intraplaque hemorrhage volume (OR = 1.7; 95% CI, 1.3-2.2), and a thin-or-ruptured fibrous cap (OR = 3.4; 95% CI, 1.7-6.7) were associated with the presence of ulcerations at baseline. In 8% (6/73) of the patients, a new ulcer developed. Plaques with a new ulceration at follow-up had at baseline a larger wall volume (1.04 cm3 [IQR, 0.97-1.16 cm3] versus 0.86 cm3 [IQR, 0.73-1.00 cm3]; P = .029), a larger relative lipid-rich necrotic core volume (23% [IQR, 13-31%] versus 2% [IQR, 0-14%]; P = .002), and a larger relative intraplaque hemorrhage volume (14% [IQR, 8-24%] versus 0% [IQR, 0-5%]; P < .001). CONCLUSIONS: Large atherosclerotic plaques and plaques with intraplaque hemorrhage and lipid-rich necrotic cores were associated with plaque ulcerations at baseline and follow-up.

Correction to: Carotid endarterectomy in patients with recurrent symptoms associated with an ipsilateral carotid artery near occlusion with full collapse.

The original version of this article unfortunately contained a mistake.

Carotid endarterectomy in patients with recurrent symptoms associated with an ipsilateral carotid artery near occlusion with full collapse.

OBJECTIVE: Near occlusion (NO) of the internal carotid artery (ICA) with full collapse (NOFC) is a rare condition, with a prevalence of around 1%. Guidelines on carotid stenosis recommend a conservative treatment in patients with a single-event ipsilateral to a NOFC, but the optimal treatment for patients with recurrent symptoms associated with NOFC remains uncertain. We describe a consecutive series of patients with recurrent symptoms associated with NOFC (RSNOFC) who underwent carotid endarterectomy (CEA). METHODS: From 2008 to 2017, 17 consecutive patients with RSNOFC were treated according to our standardized multidisciplinary work-up and protocol and included for this single-center cohort study. NO was defined according to the angiographic North American Symptomatic Carotid Endarterectomy Trial criteria. Only patients with NOFC were included in this study. RESULTS: Standard longitudinal CEA was performed in 15 patients, whereas in 2 patients the ICA was ligated with concomitant endarterectomy of the ECA. Within 30 postoperative days, one patient died from a hemorrhagic infarction. During follow-up (median 23 months) one patient died of unknown cause 90 days after CEA. No TIA, stroke, myocardial infarction or re-stenosis occurred in the remaining patients. CONCLUSION: In patients with RSNOFC, CEA may be considered a potential treatment option. Although procedural risks in this small subgroup may be higher as compared to patients with low-to-moderate risk anatomy, this risk may outbalance the natural course.

Definition of common carotid wall thickness affects risk classification in relation to degree of internal carotid artery stenosis: the Plaque At RISK (PARISK) study.

BACKGROUND: Mean or maximal intima-media thickness (IMT) is commonly used as surrogate endpoint in intervention studies. However, the effect of normalization by surrounding or median IMT or by diameter is unknown. In addition, it is unclear whether IMT inhomogeneity is a useful predictor beyond common wall parameters like maximal wall thickness, either absolute or normalized to IMT or lumen size. We investigated the interrelationship of common carotid artery (CCA) thickness parameters and their association with the ipsilateral internal carotid artery (ICA) stenosis degree. METHODS: CCA thickness parameters were extracted by edge detection applied to ultrasound B-mode recordings of 240 patients. Degree of ICA stenosis was determined from CT angiography. RESULTS: Normalization of maximal CCA wall thickness to median IMT leads to large variations. Higher CCA thickness parameter values are associated with a higher degree of ipsilateral ICA stenosis (p < 0.001), though IMT inhomogeneity does not provide extra information. When the ratio of wall thickness and diameter instead of absolute maximal wall thickness is used as risk marker for having moderate ipsilateral ICA stenosis (>50%), 55 arteries (15%) are reclassified to another risk category. CONCLUSIONS: It is more reasonable to normalize maximal wall thickness to end-diastolic diameter rather than to IMT, affecting risk classification and suggesting modification of the Mannheim criteria. TRIAL REGISTRATION: Clinical trials.gov NCT01208025 .

Prognostic significance of proteinuria in stroke patients treated with intravenous thrombolysis.

BACKGROUND AND PURPOSE: Proteinuria and estimated glomerular filtration rate (eGFR) are indicators of renal function. Whether proteinuria better predicts outcome than eGFR in stroke patients treated with intravenous thrombolysis (IVT) remains to be determined. METHODS: In this explorative multicenter IVT register based study, the presence of urine dipstick proteinuria (yes/no), reduced eGFR (<60 ml/min/1.73 m2 ) and the coexistence of both with regard to (i) poor 3-month outcome (modified Rankin Scale score 3-6), (ii) death within 3 months and (iii) symptomatic intracranial hemorrhage (ECASS-II criteria) were compared. Unadjusted and adjusted odds ratios (ORs) with 95% confidence intervals were calculated. RESULTS: Amongst 3398 patients, 881 (26.1%) had proteinuria and 623 (18.3%) reduced eGFR. Proteinuria [ORadjusted 1.65 (1.37-2.00) and ORadjusted 1.52 (1.24-1.88)] and reduced eGFR [ORadjusted 1.26 (1.01-1.57) and ORadjusted 1.34 (1.06-1.69)] were independently associated with poor functional outcome and death, respectively. After adding both renal markers to the models, proteinuria [ORadjusted+eGFR 1.59 (1.31-1.93)] still predicted poor outcome whilst reduced eGFR [ORadjusted+proteinuria 1.20 (0.96-1.50)] did not. Proteinuria was associated with symptomatic intracranial hemorrhage [ORadjusted 1.54 (1.09-2.17)] but not reduced eGFR [ORadjusted 0.96 (0.63-1.62)]. In 234 (6.9%) patients, proteinuria and reduced eGFR were coexistent. Such patients were at the highest risk of poor outcome [ORadjusted 2.16 (1.54-3.03)] and death [ORadjusted 2.55 (1.69-3.84)]. CONCLUSION: Proteinuria and reduced eGFR were each independently associated with poor outcome and death but the statistically strongest association appeared for proteinuria. Patients with coexistent proteinuria and reduced eGFR were at the highest risk of poor outcome and death.

Help seeking behavior and onset-to-alarm time in patients with acute stroke: sub-study of the preventive antibiotics in stroke study.

BACKGROUND: Patients with acute stroke often do not seek immediate medical help, which is assumed to be driven by lack of knowledge of stroke symptoms. We explored the process of help seeking behavior in patients with acute stroke, evaluating knowledge about stroke symptoms, socio-demographic and clinical characteristics, and onset-to-alarm time (OAT). METHODS: In a sub-study of the Preventive Antibiotics in Stroke Study (PASS), 161 acute stroke patients were prospectively included in 3 Dutch hospitals. A semi-structured questionnaire was used to assess knowledge, recognition and interpretation of stroke symptoms. With in-depth interviews, response actions and reasons were explored. OAT was recorded and associations with socio-demographic, clinical parameters were assessed. RESULTS: Knowledge about stroke symptoms does not always result in correct recognition of own stroke symptoms, neither into correct interpretation of the situation and subsequent action. In our study population of 161 patients with acute stroke, median OAT was 30 min (interquartile range [IQR] 10-150 min). Recognition of one-sided weakness and/or sensory loss (p = 0.046) and adequate interpretation of the stroke situation (p = 0.003), stroke at daytime (p = 0.002), severe stroke (p = 0.003), calling the emergency telephone number (p = 0.004), and transport by ambulance (p = 0.040) were associated with shorter OAT. CONCLUSION: Help seeking behavior after acute stroke is a complex process. A shorter OAT after stroke is associated with correct recognition of one-sided weakness and/or sensory loss, adequate interpretation of the stroke situation by the patient and stroke characteristics and logistics of stroke care, but not by knowledge of stroke symptoms.

The ThRombolysis in UnconTrolled Hypertension (TRUTH) protocol: an observational study on treatment strategy of elevated blood pressure in stroke patients eligible for IVT.

BACKGROUND: Intravenous thrombolysis (IVT) with (recombinant) tissue plasminogen activator is an effective treatment in acute ischemic stroke. However, IVT is contraindicated when blood pressure is above 185/110 mmHg, because of an increased risk on symptomatic intracranial hemorrhage. In current Dutch clinical practice, two distinct strategies are used in this situation. The active strategy comprises lowering blood pressure with antihypertensive agents below these thresholds to allow start of IVT. In the conservative strategy, IVT is administered only when blood pressure drops spontaneously below protocolled thresholds. A retrospective analysis in two recent stroke trials showed a non-significant signal towards better functional outcome in the active group; robust evidence for either strategy, however, is lacking. We hypothesize that (I) the active strategy leads to a better functional outcome three months after acute ischemic stroke. Secondary hypotheses are that this effect occurs despite (II) increasing the number of symptomatic intracranial hemorrhages, and could be attributable to (III) a higher rate of IVT treatments and (IV) a shorter door-to-needle time. METHODS AND DESIGN: The TRUTH is a prospective, observational, cluster-based, parallel group follow-up study; in which participating centers continue their current local treatment guidelines. Outcomes of patients admitted to centers with an active will be compared to those admitted to centers with a conservative strategy. The primary outcome is functional outcome on the modified Rankin Scale at three months. Secondary outcomes are symptomatic intracranial hemorrhage, IVT treatment and door-to-needle time. We based our sample size estimate on an ordinal analysis of the mRS with the "proportional odds" model. With the aforementioned signal observed in a recent retrospective study in these patients as an estimate of the effect size and with alpha 0 · 05, this analysis would have an 80 % power with a total number of 600 patients. Corrections for expected imbalance in group size and clustering effects resulted in a sample size of 1235 patients. DISCUSSION: The TRUTH is the first large prospective study specifically studying IVT-candidates with elevated blood pressure, and has the potential to change clinical practice and optimize acute stroke care in these patients.

Diagnostic Accuracy of 4 Commercially Available Semiautomatic Packages for Carotid Artery Stenosis Measurement on CTA.

BACKGROUND AND PURPOSE: Semiautomatic measurement of ICA stenosis potentially increases observer reproducibility. In this study, we assessed the diagnostic accuracy and interobserver reproducibility of a commercially available semiautomatic ICA stenosis measurement on CTA and estimated the agreement among different software packages. MATERIALS AND METHODS: We analyzed 141 arteries from 90 patients with TIA or ischemic stroke. Manual stenosis measurements were performed by 2 neuroradiologists. Semiautomatic measurements by using 4 methods (3mensio and comparable software from Philips, TeraRecon, and Siemens) were performed by 2 observers. Diagnostic accuracy was estimated by comparing semiautomatic with manual measurements. Interobserver reproducibility and agreement between different packages was assessed by calculation of the intraclass correlation coefficient and Bland-Altman 95% limits of agreement. False-negative classifications were retrospectively inspected by a neuroradiologist. RESULTS: There was no significant difference in the diagnostic performance of the 4 semiautomatic methods. The sensitivity for detecting ≥50% and ≥70% degree of stenosis was between 76% and 82% and 46% and 62%, respectively. Specificity and overall diagnostic accuracy were between 92% and 97% and 85% and 90%, respectively. The interobserver intraclass correlation coefficient was between 0.83 and 0.96 for semiautomatic measurements and 0.81 for manual measurement. The limits of agreement between each pair of semiautomatic packages ranged from -18%-24% to -33%-31%. False-negative classifications were caused by ulcerative plaques and observer variation in stenosis and reference measurements. CONCLUSIONS: Semiautomatic methods have a low-to-good sensitivity and a good specificity and overall diagnostic accuracy. The high interobserver reproducibility makes semiautomatic stenosis measurement valuable for clinical practice, but semiautomatic measurements should be checked by an experienced radiologist.

Intraplaque Hemorrhage and the Plaque Surface in Carotid Atherosclerosis: The Plaque At RISK Study (PARISK).

BACKGROUND AND PURPOSE: An important characteristic of vulnerable plaque, intraplaque hemorrhage, may predict plaque rupture. Plaque rupture can be visible on noninvasive imaging as a disruption of the plaque surface. We investigated the association between intraplaque hemorrhage and disruption of the plaque surface. MATERIALS AND METHODS: We selected the first 100 patients of the Plaque At RISK study, an ongoing prospective noninvasive plaque imaging study in patients with mild-to-moderate atherosclerotic lesions in the carotid artery. In carotid artery plaques, disruption of the plaque surface (defined as ulcerated plaques and/or fissured fibrous cap) and intraplaque hemorrhage were assessed by using MDCTA and 3T MR imaging, respectively. We used a χ(2) test and multivariable logistic regression to assess the association between intraplaque hemorrhage and disrupted plaque surface. RESULTS: One hundred forty-nine carotid arteries in 78 patients could be used for the current analyses. Intraplaque hemorrhage and plaque ulcerations were more prevalent in symptomatic compared with contralateral vessels (hemorrhage, 38% versus 11%; P < .001; and ulcerations, 27% versus 7%; P = .001). Fissured fibrous cap was more prevalent in symptomatic compared with contralateral vessels (13% versus 4%; P = .06). After adjustment for age, sex, diabetes mellitus, and degree of stenosis, intraplaque hemorrhage was associated with disrupted plaque surface (OR, 3.13; 95% CI, 1.25-7.84) in all vessels. CONCLUSIONS: Intraplaque hemorrhage is associated with disruption of the plaque surface in patients with a carotid artery stenosis of <70%. Serial studies are needed to investigate whether intraplaque hemorrhage indeed increases the risk of plaque rupture and subsequent ischemic stroke during follow-up.

[Downbeat nystagmus - a rare side-effect of lithium carbonate]. / Downbeatnystagmus als zeldzame bijwerking van lithiumcarbonaat.

A 52-year-old woman who had been treated with lithium carbonate for 10 years developed a downbeat nystagmus. The literature describes downbeat nystagmus as a rare side-effect of lithium carbonate. In this patient other causes of downbeat nystagmus were ruled out. In most cases stopping lithium carbonate does not alleviate the symptoms, which are often debilitating. At the moment there is no adequate treatment for the condition. In some cases, however, the symptoms subside after the patient stops taking lithium. Therefore, we consider that early recognition of downbeat nystagmus in patients being treated with lithium carbonate is vitally important.

Echographic risk index and cerebral ischemic brain lesions in patients randomized to stenting versus endarterectomy for symptomatic carotid artery stenosis.

PURPOSE: It remains to be determined whether the impact of plaque characteristics on procedural risks differs between carotid artery stenting (CAS) and endarterectomy (CEA). We studied whether quantitative assessment of carotid plaque echolucency on ultrasound predicts the risk of embolism during CAS or CEA. MATERIALS AND METHODS: In 50 consecutive patients with symptomatic carotid stenosis randomized to CAS (n = 26) or CEA (n = 24) in the International Carotid Stenting Study (ICSS), semi-automated grayscale measurement of carotid plaques on baseline ultrasound was performed. We determined the grayscale median (GSM), percentage of echolucent plaque area, and a previously defined echographic risk index (ERI) calculated with the echolucent area and degree of stenosis. Brain MRI including diffusion-weighted imaging (DWI) was performed within 7 days before and 3 days after treatment. The primary outcome was the presence of at least 1 new hyperintense DWI lesion (DWI+) after treatment. RESULTS: In the CAS group, DWI+ patients (n = 18) had a significantly higher ERI at baseline (mean 0.11 ±â€Š0.12) than patients without new lesions (n = 8; mean 0.03 ±â€Š0.01; p = 0.012). GSM (mean 26.7 ±â€Š18.7 versus 34.3 ±â€Š8.0, p = 0.16) and echolucent plaque area (mean 42.8 ±â€Š21.1 versus 31.2 ±â€Š8.2, p = 0.054) did not differ significantly. In the CEA group, there were no differences in plaque echogenity measurements between patients with (n = 2) and without DWI lesions (n = 22). CONCLUSION: Patients with echolucent plaques causing severe narrowing are at increased risk for cerebral embolism during CAS. Quantitative ultrasound plaque analysis, with ERI in particular, may add to clinical variables in identifying patients at risk for procedural stroke with CAS, but larger studies with clinical endpoints are needed.

Plaque At RISK (PARISK): prospective multicenter study to improve diagnosis of high-risk carotid plaques.

BACKGROUND: Patients with symptomatic carotid artery stenosis are at high risk for recurrent stroke. To date, the decision to perform carotid endarterectomy in patients with a recent cerebrovascular event is mainly based on degree of stenosis of the ipsilateral carotid artery. However, additional atherosclerotic plaque characteristics might be better predictors of stroke, allowing for more precise selection of patients for carotid endarterectomy. AIMS AND HYPOTHESIS: We investigate the hypothesis that the assessment of carotid plaque characteristics with magnetic resonance imaging, multidetector-row computed tomography angiography, ultrasonography, and transcranial Doppler, either alone or in combination, may improve identification of a subgroup of patients with < 70% carotid artery stenosis with an increased risk of recurrent stroke. METHODS: The Plaque At RISK (PARISK) study is a prospective multicenter cohort study of patients with recent (<3 months) neurological symptoms due to ischemia in the territory of the carotid artery and < 70% ipsilateral carotid artery stenosis who are not scheduled for carotid endarterectomy or stenting. At baseline, 300 patients will undergo magnetic resonance imaging, multidetector-row computed tomography angiography, and ultrasonography examination of the carotid arteries. In addition, magnetic resonance imaging of the brain, ambulatory transcranial Doppler recording of the middle cerebral artery and blood withdrawal will be performed. After two-years, imaging will be repeated in 150 patients. All patients undergo a follow-up brain magnetic resonance imaging, and there will be regular clinical follow-up until the end of the study. STUDY OUTCOMES: The combined primary end-point contains ipsilateral recurrent ischemic stroke or transient ischemic attack or new ipsilateral ischemic brain lesions on follow-up brain magnetic resonance imaging.

Interprocedural comparison of changes in natural flow velocity patterns in the internal carotid artery following CAS or CEA.

BACKGROUND AND PURPOSE: Different flow velocities have been reported after carotid angioplasty with stenting (CAS) than after carotid endarterectomy (CEA). We compared blood flow velocities following CAS and CEA in the International Carotid Stenting Study (ICSS; ISRCTN25337470). MATERIALS AND METHODS: In total, 254 patients (70% male; 129 CAS and 125 CEA) were included. Mean peak systolic velocities (PSVICA) were assessed at baseline, 30 days, 1 and 2 years. Following both treatments, restenosis ≥ 50% was defined as PSVmean >125 cm s(-1). RESULTS: CAS and CEA resulted in a similar reduction in PSVICA 1 month after treatment. Post-intervention analysis for each treatment separately revealed that PSVICA following CAS increased significantly during follow-up (30 days to 2 years; 22.4 cm s(-1); 95% confidence interval (CI), 14.3 to 30.5). On the contrary, PSVICA following CEA remained relatively stable during follow-up (4.7 cm s(-1); 95% CI, -6.5 to 15.9). When we analysed the increase in PSVICA between both treatments after 2 years of follow-up, no significant interprocedural difference was observed. The internal carotid artery/common carotid artery (ICA/CCA) PSV ratio increased after CAS but not after CEA: 1.2 vs. 1.1 (0.04, 95% CI; -0.16 to 0.25) at 30 days; 1.5 vs. 1.1 (0.39, 95% CI; 0.13 to 0.65) at 1 year; and 1.5 vs. 1.1 (0.36; 95% CI, 0.08 to 0.63) at 2 years. The rate of apparent ipsilateral ICA restenosis >50% was higher following CAS (hazard ratio 2.35; 95% CI, 1.35 to 4.09). CONCLUSION: Two years after carotid revascularisation, no significant interprocedural difference was observed in the increase of PSVICA between CAS and CEA. However, the ICA/CCA ratio increased more following CAS resulting in an apparent higher rate of restenosis following CAS.

Cerebral small-vessel disease and progression of brain atrophy: the SMART-MR study.

OBJECTIVES: To investigate whether severity and progression of periventricular and deep white matter lesions (WML) and lacunar infarcts were associated with progression of brain atrophy. METHODS: Within the SMART-MR study, a prospective cohort on MRI changes in patients with symptomatic atherosclerotic disease, 565 patients (57 ± 9 years) without large infarcts had vascular screening and 1.5 T MRI at baseline and after a mean follow-up of 3.9 years. With automated brain segmentation, total brain, cortical gray matter, ventricular, and WML volumes were estimated and expressed relative to intracranial volume (%). Lacunar infarcts were rated manually. RESULTS: Using linear regression analyses adjusted for demographics and vascular risk factors, periventricular WML volume at baseline was associated with greater decrease in cortical gray matter volume (B = -1.73%, 95% confidence interval [CI] -3.15% to -0.30%, per 1% WML volume increase) and greater increase in ventricular volume (B = 0.12%, 95% CI 0.04% to 0.20%). Progression of periventricular WML volume corresponded with a greater decrease in cortical gray matter volume (B = -0.45%, 95% CI -0.9% to 0%) and greater increase in ventricular volume (B = 0.15%, 95% CI 0.1% to 0.2%). Presence of lacunar infarcts was associated with greater decline in total brain volume (B = -0.25%, 95% CI -0.49% to -0.01%) and progression of lacunar infarcts with a greater decrease of total brain (B = -0.30%, 95% CI -0.59% to 0.01%) and cortical gray matter volume (B = -0.81%, 95% CI -1.43% to -0.20%). CONCLUSIONS: In patients with symptomatic atherosclerotic disease, presence and progression of periventricular WML and lacunar infarcts is associated with greater progression of brain atrophy independent of vascular risk factors.