Clinical impact and predictors of carotid artery in-stent restenosis.

To assess the incidence and clinical significance as well as predictors of in-stent restenosis (ISR) after carotid artery stenting (CAS) diagnosed with serial duplex sonography investigations. We analyzed 215 CAS procedures that had clinical and serial carotid duplex ultrasound investigations. The incidence of in-stent restenosis (ISR) and periprocedural as well as long-term clinical complications were recorded. The influence of an ISR on clinical complication was analyzed using Kaplan-Meier curves and clinical risk factors for the development of an ISR with multivariate logistic regression. During a median follow-up time of 33.4 months (interquartile range 15.3-53.7) an ISR of ≥70% was detected in 12 (6.1%) of 215 arteries (mean age of 68.1 ± 9.8 years, 71.6% male). The combined stroke and death rate during long-term follow-up was significantly higher in the group with an ISR [odds ratio (OR): 3.59, 95% confidence interval (CI): 1.50-8.59, p = 0.004]. After applying multivariate logistic regression analysis contralateral carotid occlusion (OR 10.11, 95% CI 2.06-49.63, p = 0.004), carotid endarterectomy (CEA) restenosis (OR 8.87, 95% CI 1.68-46.84, p = 0.010) and postprocedural carotid duplex ultrasound with a PSV ≥120 cm/s (OR 6.33, 95% CI 1.27-31.44, p = 0.024) were independent predictors of ISR. ISR after CAS during long-term follow-up is associated with a higher proportion of clinical complications. A close follow-up is suggested especially in those patients with the aforementioned independent predictors of an ISR. Against the background of a lacking established treatment of ISR, these findings should be taken into account when offering CAS as a treatment alternative to CEA.

Growth-differentiation factor-15 and functional outcome after acute ischemic stroke.

Blood biomarkers may improve the performance in predicting early stroke outcome beyond well-established clinical factors. We investigated the value of growth-differentiation factor-15 (GDF-15) to predict functional outcome after 90 days in a prospectively collected patient cohort with symptoms of acute ischemic stroke. Two hundred eighty-one patients with symptoms of acute ischemic stroke were prospectively investigated. Serial blood samples for GDF-15 analysis were obtained after the admission of the patient, after 6 and 24 h. Primary outcome was the dichotomized modified ranking scale (MRS) 90 days after the initial clinical event. Within the final study population (264 patients, mean age 70.3 ± 12.7 years, 55.3% male), National Institutes of Health Stroke Scale (NIH-SS) [odds ratio (OR) 1.269, 95% confidence interval (CI) 1.141-1.412, p < 0.001] and initial GDF-15 levels (OR 1.029, 95% CI 1.007-1.053, p = 0.011) were independently associated with a MRS ≥ 2 after day 90 after multiple regression analysis. Growth-differentiation factor-15 levels increase with higher NIH-SS-tertiles (p = 0.005). Receiver-operator characteristic curves demonstrated a discriminatory accuracy to predict unfavourable stroke outcome of 0.629 (95% CI 0.558-0.699), 0.753 (95% CI 0.693-812) and 0.774 (95% CI 0.717-0.832) for GDF-15, NIH-SS and the combination of these variables. The additional use of GDF-15 to NIH-SS ameliorates the model with a net reclassification index of 0.044 (p = 0.541) and integrated discrimination improvement of 0.034 (p = 0.443). Growth-differentiation factor-15 as an acute stroke biomarker independently predicts unfavourable functional 90 day stroke outcome. Discriminatory value in addition to NIH-SS is only modestly distinct.

Inflammation and in-stent restenosis: the role of serum markers and stent characteristics in carotid artery stenting.

BACKGROUND: Carotid angioplasty and stenting (CAS) may currently be recommended especially in younger patients with a high-grade carotid artery stenosis. However, evidence is accumulating that in-stent restenosis (ISR) could be an important factor endangering the long-term efficacy of CAS. The aim of this study was to investigate the influence of inflammatory serum markers and procedure-related factors on ISR as diagnosed with duplex sonography. METHODS: We analyzed 210 CAS procedures in 194 patients which were done at a single university hospital between May 2003 and June 2010. Periprocedural C-reactive protein (CRP) and leukocyte count as well as stent design and geometry, and other periprocedural factors were analyzed with respect to the occurrence of an ISR as diagnosed with serial carotid duplex ultrasound investigations during clinical long-term follow-up. RESULTS: Over a median of 33.4 months follow-up (IQR: 14.9-53.7) of 210 procedures (mean age of 67.9±9.7 years, 71.9% male, 71.0% symptomatic) an ISR of ≥70% was detected in 5.7% after a median of 8.6 months (IQR: 3.4-17.3). After multiple regression analysis, leukocyte count after CAS-intervention (odds ratio (OR): 1.31, 95% confidence interval (CI): 1.02-1.69; p = 0.036), as well as stent length and width were associated with the development of an ISR during follow-up (OR: 1.25, 95% CI: 1.05-1.65, p = 0.022 and OR: 0.28, 95% CI: 0.09-0.84, p = 0.010). CONCLUSIONS: The majority of ISR during long-term follow-up after CAS occur within the first year. ISR is associated with periinterventional inflammation markers and influenced by certain stent characteristics such as stent length and width. Our findings support the assumption that stent geometry leading to vessel injury as well as periprocedural inflammation during CAS plays a pivotal role in the development of carotid artery ISR.

Factors associated with time delay to carotid stenting in patients with a symptomatic carotid artery stenosis.

Treatment of a symptomatic stenosis is known to be most beneficial within 14 days after the presenting event but this can frequently not be achieved in daily practice. The aim of this study was the assessment of factors responsible for this time delay to treatment. A retrospective analysis of a prospective two-center CAS database was carried out to investigate the potential factors that influence a delayed CAS treatment. Of 374 patients with a symptomatic carotid stenosis, 59.1% were treated beyond ≥14 days. A retinal TIA event (OR = 3.59, 95% CI 1.47-8.74, p < 0.01) was found to be a predictor for a delayed treatment, whereas the year of the intervention (OR = 0.32, 95% CI 0.20-0.50, p < 0.01) and a contralateral carotid occlusion (OR = 0.42, 95% CI 0.21-0.86, p = 0.02) were predictive of an early treatment. Similarly, within the subgroup of patients with transient symptoms, the year of the intervention (OR = 0.28, 95% CI 0.14-0.59, p < 0.01) was associated with an early treatment, whereas a retinal TIA as the qualifying event (OR = 6.96, 95% CI 2.37-20.47, p < 0.01) was associated with a delayed treatment. Treatment delay was most pronounced in patients with an amaurosis fugax, whereas a contralateral carotid occlusion led to an early intervention. Although CAS is increasingly performed faster in the last years, there is still scope for an even more accelerated treatment strategy, which might prevent future recurrent strokes prior to treatment.

New brain lesions after carotid revascularization are not associated with cognitive performance.

PURPOSE: Carotid angioplasty and stenting (CAS) is increasingly being used as a treatment alternative to endarterectomy (CEA) for patients with significant carotid stenosis. However, diffusion-weighted imaging (DWI) has indicated that CAS is associated with a significantly higher burden of microemboli. This study evaluated the potential effect on intellectual functions of new DWI lesions after CEA or CAS. METHODS: This prospective study analyzed the neuropsychologic outcomes after revascularization in 24 CAS and 31 CEA patients with severe carotid stenosis compared with a control group of 27 healthy individuals. All patients underwent clinical examinations, magnetic resonance imaging scans, and a neuropsychologic test battery that assessed six major cognitive domains performed immediately before CEA or CAS, ≤ 72 hours after, and at 3 months. RESULTS: New DWI lesions were detected among 15 of 21 (71%) of the CAS patients immediately after treatment but in only 1 of the 28 CEA patients (4%; P < .01). As a group, patients with new DWI lesions showed a decline in their performance in the cognitive domains, attention, and visuoconstructive functions within 72 hours of carotid revascularization. Individually, however, in none of the cognitive domains did the decreases reach a clinically relevant threshold of z < -1.5. Moreover, the cognitive performance was not significantly different between patients with and without new DWI lesions 3 months after treatment. The cognitive performance was similar between CEA and CAS patients at all points. CONCLUSIONS: The findings support the assumption that new brain lesions, as detected with DWI after CAS or CEA, do not affect cognitive performance in a manner that is long-lasting or clinically relevant. Despite the higher embolic load detected by DWI, CAS is not associated with a greater cognitive decline than CEA.

The role of the unaffected hemisphere in motor recovery after stroke.

The contribution of the ipsilateral (nonaffected) hemisphere to recovery of motor function after stroke is controversial. Under the assumption that functionally relevant areas within the ipsilateral motor system should be tightly coupled to the demand we used fMRI and acoustically paced movements of the right index finger at six different frequencies to define the role of these regions for recovery after stroke. Eight well-recovered patients with a chronic striatocapsular infarction of the left hemisphere were compared with eight age-matched participants. As expected the hemodynamic response increased linearly with the frequency of the finger movements at the level of the left supplementary motor cortex (SMA) and the left primary sensorimotor cortex (SMC) in both groups. In contrast, a linear increase of the hemodynamic response with higher tapping frequencies in the right premotor cortex (PMC) and the right SMC was only seen in the patient group. These results support the model of an enhanced bihemispheric recruitment of preexisting motor representations in patients after subcortical stroke. Since all patients had excellent motor recovery contralesional SMC activation appears to be efficient and resembles the widespread, bilateral activation observed in healthy participants performing complex movements, instead of reflecting maladaptive plasticity.

Positional brain deformation visualized with magnetic resonance morphometry.

OBJECTIVE: To assess and visualize gravitational effects on brain morphology and the position of the brain within the skull by magnetic resonance (MR) morphometry in order to identify confounding effects and possible sources of error for accurate planning of neurosurgical interventions. METHODS: Three-dimensional MR imaging data sets of 13 healthy adults were acquired in different positions in the scanner. With a morphometric approach, data sets were evaluated by deformation field analysis and the brain boundary shift integral. Distortions of the brain were assessed comparing right versus left and prone versus supine positioning, respectively. RESULTS: Two effects could be differentiated: 1) greatest brain deformation of up to 1.7 mm predominantly located around central brain structures in the lateral direction and a less pronounced change after position changes in posterior-anterior direction, and 2) the brain boundary shift integral depicted position-dependent brain shift relative to the inner skull. CONCLUSION: Position-dependent effects on brain structure may undermine the accuracy of neuronavigational and other neurosurgical procedures. Furthermore, in longitudinal MR volumetric studies, gravitational effects should be kept in mind and the scanning position should be rigidly controlled for.

Noninvasive assessment of cerebral perfusion and oxygenation in acute ischemic stroke by near-infrared spectroscopy.

BACKGROUND: In acute stroke patients, there is a need for noninvasive measurement to monitor blood flow-based therapies. We investigated the utility of near-infrared spectroscopy (NIRS) to determine cerebral perfusion in these patients. METHODS: Eleven patients were investigated within 1.4 +/- 2.2 days after onset of an ischemic middle cerebral artery infarction by monitoring the kinetics of an intravenous bolus of indocyanine green (ICG). For ICG kinetics, bolus peak time, time to peak (TTP = time between 0 and 100% ICG maximum), maximum ICG concentration, rise time (time between 10 and 90% ICG maximum), slope (maximum ICG/TTP), and blood flow index (BFI = maximum ICG/rise time) were obtained. Perfusion-weighted MRI (PWI) and NIRS measurements were performed within 24 h, and the interhemispherical differences of TTP values were compared. RESULTS: Stroke patients showed an increased bolus peak time (p < 0.02), TTP (p < 0.01), and rise time (p < 0.01), whereas slope (p < 0.01) and BFI (p < 0.01) were diminished at the site of infarction as compared to the unaffected hemisphere. The interhemispherical differences of TTP as measured by PWI and NIRS were closely correlated (r = 0.86). CONCLUSIONS: Noninvasive measurements of cerebral ICG kinetics by NIRS provide a useful means of detecting cerebral perfusion deficits in patients with acute stroke, which correlate well with those obtained by PWI.

A systematic review on outcome after stenting for intracranial atherosclerosis.

BACKGROUND AND PURPOSE: Angioplasty and stenting is increasingly being used for the treatment of intracranial stenoses. Based on a literature search (01/1998 to 04/2008) we sought to determine the immediate and long-term outcomes, as well as the durability of this procedure. SUMMARY OF REVIEW: We identified 31 studies dealing with 1177 procedures, which had mainly been performed in patients with a symptomatic (98%) intracranial high-grade stenosis (mean: 78+/-7%) at high technical success rates (median: 96%; interquartile range [IQR]: 90% to 100%). The periprocedural minor or major stroke and death rates ranged from 0% to 50% with a median of 7.7% (IQR: 4.4% to 14.3%). Periprocedural complications were significantly higher in the posterior versus the anterior circulation (12.1%, versus 6.6%, P<0.01, odds ratio [OR]: 1.94, 95% confidence interval [CI]: 1.21 to 3.10), but did not differ between patients treated with a balloon-mounted (n=906) versus those who had been treated with a self-expandable stent (n=271; 9.5% versus 7.7%, P=0.47, OR: 1.15, CI:0.76 to 2.05). Restenosis >50% occurred more frequently after the use of a self-expandable stent (16/92; 17.4%, mean follow-up time: 5.4 months) than a balloon-mounted stent (61/443; 13.8%, mean follow-up time: 8.7 months; P<0.001, log-rank test). CONCLUSIONS: Although intracranial stenting appears to be feasible, adverse events vary widely. Against the background of the results of this review yielding a high rate of restenoses and no clear impact of new stent devices on outcome, the widespread application of intracranial stenting outside the setting of randomized trials and in inexperienced centers currently does not seem to be justified.

Carotid artery disease: stenting versus endarterectomy.

Atherosclerotic carotid artery stenosis is a major cause of disabling stroke or death. Although carotid endarterectomy (CEA) is currently considered to be the standard of care for patients with a severe symptomatic stenosis and selected patients with an asymptomatic carotid stenosis, carotid angioplasty and stenting (CAS) is increasingly being used as an alternative treatment modality. This article briefly summarizes the current trial data on CEA and CAS. More importantly, potential risk factors for CEA and CAS are reviewed and the complementary role of these techniques in the management of the individual patient is discussed.

A risk score to predict ischemic lesions after protected carotid artery stenting.

BACKGROUND AND PURPOSE: While carotid artery stenting can be performed safely in many patients, some have a higher risk for periprocedural complications. The detection of embolic lesions after CAS with DWI could become a useful means to identify these patients. The aim of this study was to determine risk factors for new DWI lesions after CAS. METHODS: One hundred seventy-six patients who had undergone protected CAS with pre- and postprocedural DWI between November 2000 and December 2006 were included in this retrospective investigation. The association of potential angiographic and clinical risk factors with the incidence of any new ipsilateral DWI lesion after CAS was analyzed with logistic regression analysis. Subsequently, a simple risk score was developed using area under the curve (ROC) statistics. RESULTS: The proportion of patients with any new ipsilateral DWI lesion was 51%. Advanced age (odds ratio (OR) 1.06; 95% confidence interval (CI) 1.01-1.11, p=0.008), the presence of an ulcerated stenosis (OR 2.28: 95% CI 1.10-4.75; p=0.027) or a lesion length>1 cm (OR 2.65; 95% CI 1.33-5.28, p=0.006) were independent risk factors for new ipsilateral DWI lesions. A 4 point score ranging from 0 to 4 (age> or =70 years=1 point, age> or =80 years=2 points, lesion length>1 cm=1 point, and presence of an ulcerated stenosis=1 point) reliably predicted the incidence of this outcome parameter (ROC=0.70, p<0.001). CONCLUSIONS: A simple risk score can be used to identify patients at a high risk for new DWI lesions as a possible surrogate of embolic complications after CAS.

Behavioral correlates of negative BOLD signal changes in the primary somatosensory cortex.

Functional magnetic resonance imaging (fMRI) hypothesis testing based on the blood oxygenation level dependent (BOLD) contrast mechanism typically involves a search for a positive effect during a specific task relative to a control state. However, aside from positive BOLD signal changes there is converging evidence that neuronal responses within various cortical areas also induce negative BOLD signals. Although it is commonly believed that these negative BOLD signal changes reflect suppression of neuronal activity direct evidence for this assumption is sparse. Since the somatosensory system offers the opportunity to quantitatively test sensory function during concomitant activation and has been well-characterized with fMRI in the past, the aim of this study was to determine the functional significance of ipsilateral negative BOLD signal changes during unilateral sensory stimulation. For this, we measured BOLD responses in the somatosensory system during unilateral electric stimulation of the right median nerve and additionally determined the current perception threshold of the left index finger during right-sided electrical median nerve stimulation as a quantitative measure of sensory function. As expected, positive BOLD signal changes were observed in the contralateral primary and bilateral secondary somatosensory areas, whereas a decreased BOLD signal was observed in the ipsilateral primary somatosensory cortex (SI). The negative BOLD signal changes were much more spatially extensive than the representation of the hand area within the ipsilateral SI. The negative BOLD signal changes in the area of the index finger highly correlated with an increase in current perception thresholds of the contralateral, unstimulated finger, thus supporting the notion that the ipsilateral negative BOLD response reflects a functionally effective inhibition in the somatosensory system.

New brain lesions after carotid stenting versus carotid endarterectomy: a systematic review of the literature.

BACKGROUND AND PURPOSE: Against the background of a relatively low rate of clinical events during carotid angioplasty and stenting (CAS) or carotid endarterectomy (CEA), diffusion-weighted imaging (DWI) is increasingly being used to compare the incidence of new ischemic lesions after both procedures. In addition, DWI may also provide a means of defining the role of different CAS techniques on this adverse outcome. Therefore, we performed a PubMed search and systematically analyzed all peer-reviewed studies published between January 1990 and June 2007 reporting on the occurrence of new DWI lesions after CAS or CEA. Summary of Review- In 32 studies comprising 1363 CAS and 754 CEA procedures, the incidence of any new DWI lesion was significantly higher after CAS (37%) than after CEA (10%) (P<0.01). Similar results were obtained in a meta-analysis focusing on those studies directly comparing the incidence of new DWI lesions after either CEA or CAS (OR, 6.1; 95% CI, 4.19 to 8.87; P<0.01). The use of cerebral protection devices (33% vs 45% without; P<0.01) and closed-cell designed stents during CAS (31% vs 51% with open-cell stents; P<0.01), as well as selective versus routine shunt usage during CEA (6% vs 16%; P<0.01) significantly reduced the incidence of new ipsilateral DWI lesions. CONCLUSIONS: New DWI lesions occur more frequently after CAS than after CEA. However, technical advances mainly in the field of endovascular therapy potentially reduce the incidence of these adverse ischemic events. In this scenario, DWI appears to be an ideal tool to compare and further improve both techniques.

Target lesion ulceration and arch calcification are associated with increased incidence of carotid stenting-associated ischemic lesions in octogenarians.

PURPOSE: Although evidence is accumulating that advanced age is a risk factor for carotid angioplasty and stenting (CAS), the reason for this finding is incompletely understood. The aims of this study were to compare the prevalence of anatomic risk factors in patients <80 years with those in patients > or =80 years and to determine the effect of these risk factors on the incidence of new lesions seen on diffusion-weighted imaging (DWI) after protected CAS as surrogate markers for stroke. METHODS: Various potential anatomic risk factors for CAS were analyzed in 62 symptomatic patients (49 aged <80 years; 13 aged > or =80 years) by using preprocedural digital subtraction angiograms and extracranial contrast-enhanced magnetic resonance angiographies. DWI was performed immediately before and or =80 years) were not significant, the proportion of patients with any new ipsilateral DWI lesions, as well as the total number of these lesions, was higher in octogenarians than in patients aged <80 years (85% vs 47%, P < .05), with a median of 2 (interquartile range [IQR], 1 to 5) vs 0 (IQR, 0 to 3; P = .07). Similarly, the proportion of patients with any new DWI lesions outside the vascular territory of the target vessel as well as the total number of these lesions was significantly higher in octogenarians compared with patients aged <80 years (54% vs 10%, P < .01), with a median of 1.5 (IQR, 0.25 to 10.75) vs 0 (IQR, 0 to 1; P < .05). The presence of an ulcerated lesion was an independent predictor of any new ipsilateral DWI lesion (odds ratio [OR], 4.3; 95% confidence interval [CI], 1.06 to 17.1; P < .05), whereas a severe aortic arch calcification tended to be a predictor of new DWI lesions outside the territory of the treated artery (OR, 1.8; 95% CI, 0.99 to 3335; P = .05). CONCLUSIONS: Increased prevalences of severe aortic arch calcifications and target lesion ulceration are associated with an increased risk for magnetic resonance DWI-detected embolic events during CAS. Because in our study arch calcification and target lesion ulceration were more prevalent in octogenarians, this association may explain the increased risk of CAS in the elderly.