Coiling of the Internal Carotid Artery is Associated with Hypertension in Patients Suspected of Stroke

PURPOSE: The etiology of coiling (i.e. severe elongation) of the extracranial part of the internal carotid artery (ICA) is poorly understood with the proposed etiology being congenital, atherosclerotic or hypertension. The objective was to investigate the association of coiling with hypertension, carotid artery atherosclerosis and other cardiovascular risk factors. METHODS: A case control study was performed in patients suspected of stroke, with (cases) or without (controls) coiling of the ICA determined on compute tomography angiography (CTA). Baseline characteristics included age, gender, hypertension, diabetes, smoking and hypercholesterolemia. Coiling of the ICA and atherosclerotic plaque at the carotid bifurcation were assessed on CTA. Logistic regression analyses were conducted. RESULTS: Coiling was identified in 108 patients with a median age of 71 years. Cases were compared with 256 controls with a median age of 69 years. Hypertension was present in 63% of the patients with coiling compared to 51% in the control group. Univariable analysis showed that hypertension was significantly associated with coiling, with an odds ratio of 1.65 (95% confidence interval (CI) 1.04-2.61, p = 0.034). Multivariable analysis corrected for age and sex resulted in an odds ratio of 1.71 (95% CI 1.05-2.80, p = 0.032), while correcting for atherosclerotic plaque at the bifurcation yielded an odds ratio of 1.63 (95% CI 1.00-2.66, p = 0.049). Age and atherosclerotic plaque were not significantly associated with coiling. CONCLUSION: The main finding of this study was the significant association of hypertension with coiling of the ICA and the absence of an association with age, plaques and atherosclerotic risk factors other than hypertension

Effect of intravenous thrombolysis in stroke depends on pattern of intracranial internal carotid artery calcification

BACKGROUND AND AIMS: The pattern of intracranial internal carotid artery calcification (ICAC) has been identified as an effect modifier of endovascular treatment in patients with acute ischemic stroke, but it is unclear whether it modifies the effect of intravenous thrombolysis. The purpose of this study was to evaluate the association between intravenous thrombolysis and 90-day clinical outcome, follow-up infarct volume, intracranial hemorrhage and recanalization across different patterns of ICAC. METHODS: Patients with acute ischemic stroke were selected from the Dutch acute stroke study, a prospective multicenter observational cohort study. ICAC pattern was determined on admission thin-slice non-contrast CT and categorized as absent, intimal, medial or indistinguishable. The primary outcome was the ordinal 90-day modified Rankin Scale. Other outcomes included follow-up infarct volume, intracranial hemorrhage, recanalization and collateral status. Associations were quantified with regression analyses and stratified by ICAC pattern. RESULTS: Of 982 patients, 609 (62%) received intravenous thrombolysis and 381 (39%) had a 90-day modified Rankin Scale of 3-6. Intravenous thrombolysis was associated with a lower 90-day modified Rankin Scale in the group without ICAC (adjusted OR 0.3; 95%-CI 0.1-0.9) and in the group with a medial ICAC pattern (adjusted OR 0.5; 95%-CI 0.3-0.8), but not in the groups with intimal (adjusted OR 0.9; 95%-CI 0.5-1.5) or indistinguishable patterns (adjusted OR 0.6; 95%-CI 0.2-1.8). The associations between intravenous thrombolysis and follow-up infarct volume and intracranial hemorrhage were not significant for any of the ICAC pattern groups. Intravenous thrombolysis was only associated with recanalization in the group with a medial ICAC pattern (adjusted OR 3.5; 95%-CI 1.2-11.0). Compared to an intimal ICAC pattern, a medial ICAC pattern was associated with good collateral status (adjusted OR 2.6; 95%-CI 1.1-6.0). CONCLUSIONS: Intravenous thrombolysis was significantly associated with favorable clinical outcome and successful recanalization in the group with a medial ICAC pattern, but not in the group with an intimal ICAC pattern

Prediction of long-term recurrent ischemic stroke: the added value of non-contrast CT, CT perfusion, and CT angiography

PURPOSE: The aim of this study was to evaluate whether the addition of brain CT imaging data to a model incorporating clinical risk factors improves prediction of ischemic stroke recurrence over 5 years of follow-up. METHODS: A total of 638 patients with ischemic stroke from three centers were selected from the Dutch acute stroke study (DUST). CT-derived candidate predictors included findings on non-contrast CT, CT perfusion, and CT angiography. Five-year follow-up data were extracted from medical records. We developed a multivariable Cox regression model containing clinical predictors and an extended model including CT-derived predictors by applying backward elimination. We calculated net reclassification improvement and integrated discrimination improvement indices. Discrimination was evaluated with the optimism-corrected c-statistic and calibration with a calibration plot. RESULTS: During 5 years of follow-up, 56 patients (9%) had a recurrence. The c-statistic of the clinical model, which contained male sex, history of hyperlipidemia, and history of stroke or transient ischemic attack, was 0.61. Compared with the clinical model, the extended model, which contained previous cerebral infarcts on non-contrast CT and Alberta Stroke Program Early CT score greater than 7 on mean transit time maps derived from CT perfusion, had higher discriminative performance (c-statistic 0.65, P = 0.01). Inclusion of these CT variables led to a significant improvement in reclassification measures, by using the net reclassification improvement and integrated discrimination improvement indices. CONCLUSION: Data from CT imaging significantly improved the discriminatory performance and reclassification in predicting ischemic stroke recurrence beyond a model incorporating clinical risk factors only

Variation in arterial input function in a large multicenter computed tomography perfusion study

Objectives: To report the variation in computed tomography perfusion (CTP) arterial input function (AIF) in a multicenter stroke study and to assess the impact this has on CTP results. Methods: CTP datasets from 14 different centers were included from the DUtch acute STroke (DUST) study. The AIF was taken as a direct measure to characterize contrast bolus injection. Statistical analysis was applied to evaluate differences in amplitude, area under the curve (AUC), bolus arrival time (BAT), and time to peak (TTP). To assess the clinical relevance of differences in AIF, CTP acquisitions were simulated with a realistic anthropomorphic digital phantom. Perfusion parameters were extracted by CTP analysis using commercial software (IntelliSpace Portal (ISP), version 10.1) as well as an in-house method based on block-circulant singular value decomposition (bSVD). Results: A total of 1422 CTP datasets were included, ranging from 6 to 322 included patients per center. The measured values of the parameters used to characterize the AIF differed significantly with approximate interquartile ranges of 200–750 HU for the amplitude, 2500–10,000 HU·s for the AUC, 0–17 s for the BAT, and 10–26 s for the TTP. Mean infarct volumes of the phantom were significantly different between centers for both methods of perfusion analysis. Conclusions: Although guidelines for the acquisition protocol are often provided for centers participating in a multicenter study, contrast medium injection protocols still vary. The resulting volumetric differences in infarct core and penumbra may impact clinical decision making in stroke diagnosis. Key Points: • The contrast medium injection protocol may be different between stroke centers participating in a harmonized multicenter study. • The contrast medium injection protocol influences the results of X-ray computed tomography perfusion imaging. • The contrast medium injection protocol can impact stroke diagnosis and patient selection for treatment

Spatial CT perfusion data helpful in automatically locating vessel occlusions for acute ischemic stroke patients

Introduction: Locating a vessel occlusion is important for clinical decision support in stroke healthcare. The advent of endovascular thrombectomy beyond proximal large vessel occlusions spurs alternative approaches to locate vessel occlusions. We explore whether CT perfusion (CTP) data can help to automatically locate vessel occlusions. Methods: We composed an atlas with the downstream regions of particular vessel segments. Occlusion of these segments should result in the hypoperfusion of the corresponding downstream region. We differentiated between seven-vessel occlusion locations (ICA, proximal M1, distal M1, M2, M3, ACA, and posterior circulation). We included 596 patients from the DUtch acute STroke (DUST) multicenter study. Each patient CTP data set was processed with perfusion software to determine the hypoperfused region. The downstream region with the highest overlap with the hypoperfused region was considered to indicate the vessel occlusion location. We assessed the indications from CTP against expert annotations from CTA. Results: Our atlas-based model had a mean accuracy of 86% and could achieve substantial agreement with the annotations from CTA according to Cohen's kappa coefficient (up to 0.68). In particular, anterior large vessel occlusions and occlusions in the posterior circulation could be located with an accuracy of 80 and 92%, respectively. Conclusion: The spatial layout of the hypoperfused region can help to automatically indicate the vessel occlusion location for acute ischemic stroke patients. However, variations in vessel architecture between patients seemed to limit the capacity of CTP data to distinguish between vessel occlusion locations more accurately

Standardizing the estimation of ischemic regions can harmonize CT perfusion stroke imaging

OBJECTIVES: We aimed to evaluate the real-world variation in CT perfusion (CTP) imaging protocols among stroke centers and to explore the potential for standardizing vendor software to harmonize CTP images. METHODS: Stroke centers participating in a nationwide multicenter healthcare evaluation were requested to share their CTP scan and processing protocol. The impact of these protocols on CTP imaging was assessed by analyzing data from an anthropomorphic phantom with center-specific vendor software with default settings from one of three vendors (A-C): IntelliSpace Portal, syngoVIA, and Vitrea. Additionally, standardized infarct maps were obtained using a logistic model. RESULTS: Eighteen scan protocols were studied, all varying in acquisition settings. Of these protocols, seven, eight, and three were analyzed with center-specific vendor software A, B, and C respectively. The perfusion maps were visually dissimilar between the vendor software but were relatively unaffected by the acquisition settings. The median error [interquartile range] of the infarct core volumes (mL) estimated by the vendor software was - 2.5 [6.5] (A)/ - 18.2 [1.2] (B)/ - 8.0 [1.4] (C) when compared to the ground truth of the phantom (where a positive error indicates overestimation). Taken together, the median error [interquartile range] of the infarct core volumes (mL) was - 8.2 [14.6] before standardization and - 3.1 [2.5] after standardization. CONCLUSIONS: CTP imaging protocols varied substantially across different stroke centers, with the perfusion software being the primary source of differences in CTP images. Standardizing the estimation of ischemic regions harmonized these CTP images to a degree. CLINICAL RELEVANCE STATEMENT: The center that a stroke patient is admitted to can influence the patient's diagnosis extensively. Standardizing vendor software for CT perfusion imaging can improve the consistency and accuracy of results, enabling a more reliable diagnosis and treatment decision. KEY POINTS: • CT perfusion imaging is widely used for stroke evaluation, but variation in the acquisition and processing protocols between centers could cause varying patient diagnoses. • Variation in CT perfusion imaging mainly arises from differences in vendor software rather than acquisition settings, but these differences can be reconciled by standardizing the estimation of ischemic regions. • Standardizing the estimation of ischemic regions can improve CT perfusion imaging for stroke evaluation by facilitating reliable evaluations independent of the admission center

Intracranial Cerebrospinal Fluid Volume as a Predictor of Malignant Middle Cerebral Artery Infarction

Background and Purpose— Predicting malignant middle cerebral artery (MCA) infarction can help to identify patients who may benefit from preventive decompressive surgery. We aimed to investigate the association between the ratio of intracranial cerebrospinal fluid (CSF) volume to intracranial volume (ICV) and malignant MCA infarction. Methods— Patients with an occlusion proximal to the M3 segment of the MCA were selected from the DUST (Dutch Acute Stroke Study). Admission imaging included noncontrast computed tomography (CT), CT perfusion, and CT angiography. Patient characteristics and CT findings were collected. The ratio of intracranial CSF volume to ICV (CSF/ICV) was quantified on admission thin-slice noncontrast CT. Malignant MCA infarction was defined as a midline shift of >5 mm on follow-up noncontrast CT, which was performed 3 days after the stroke or in case of clinical deterioration. To test the association between CSF/ICV and malignant MCA infarction, odds ratios and 95% CIs were calculated for 3 multivariable models by using binary logistic regression. Model performances were compared by using the likelihood ratio test. Results— Of the 286 included patients, 35 (12%) developed malignant MCA infarction. CSF/ICV was independently associated with malignant MCA infarction in 3 multivariable models: (1) with age and admission National Institutes of Health Stroke Scale (odds ratio, 3.3; 95% CI, 1.1–11.1), (2) with admission National Institutes of Health Stroke Scale and poor collateral score (odds ratio, 7.0; 95% CI, 2.6–21.3), and (3) with terminal internal carotid artery or proximal M1 occlusion and poor collateral score (odds ratio, 7.7; 95% CI, 2.8–23.9). The performance of model 1 (areas under the receiver operating characteristic curves, 0.795 versus 0.824; P=0.033), model 2 (areas under the receiver operating characteristic curves, 0.813 versus 0.850; P<0.001), and model 3 (areas under the receiver operating characteristic curves, 0.811 versus 0.856; P<0.001) improved significantly after adding CSF/ICV. Conclusions— The CSF/ICV ratio is associated with malignant MCA infarction and has added value to clinical and imaging prediction models in limited numbers of patients

Prevalence and vascular risk factors of basal ganglia calcifications in patients at risk for cerebrovascular disease

Background and purpose: Risk factors for and meaning of basal ganglia calcifications outside Fahr syndrome are poorly understood. We aimed to assess the prevalence of basal ganglia calcifications and the association with vascular risk factors. Materials and methods: 1133 patients suspected of acute ischemic stroke from the Dutch acute stroke (DUST)study who underwent thin-slice unenhanced brain CT were analyzed. Basal ganglia calcifications were scored bilaterally as absent, mild (dot), moderate (multiple dots or single artery)and severe (confluent). Uni- and multivariable logistic regression analysis was used to determine possible risk factors (age, gender, history of stroke, smoking, hypertension, diabetes mellitus, hyperlipidemia, body mass index (BMI), renal function and family history of cardiovascular disease under 60 years)for presence of basal ganglia calcifications and ordinal regression analysis for severity of basal ganglia calcifications. Results: Mean age was 67.4 years (SD: 13.8), 56.8% were male. 337 (29.7%)patients had basal ganglia calcifications, of which 196 (58%)were mild, 103 (31%)moderate, 38 (11%)severe. In multivariable logistic regression analysis, age (OR: 1.02, 95% CI 1.01–1.03, P < 0.01)and BMI (OR: 0.95, 95% CI 0.91–0.98, p 0.01)were significantly associated with the presence of basal ganglia calcifications. Ordinal regression analysis gave comparable results. Age (OR: 1.02, 95% CI 1.01–1.03, P < 0.01)and BMI (OR: 0.95, 95% CI 0.92–0.99, P 0.01)were significantly associated with severity of basal ganglia calcifications. Conclusions: In this study with patients suspected of acute ischemic stroke, basal ganglia calcifications were common and significantly associated with older age and lower BMI

No Relation between Body Temperature and Arterial Recanalization at Three Days in Patients with Acute Ischaemic Stroke

Background Recanalization of an occluded intracranial artery is influenced by temperature-dependent enzymes, including alteplase. We assessed the relation between body temperature on admission and recanalization. Methods We included 278 patients with acute ischaemic stroke within nine hours after symptom onset, who had an intracranial arterial occlusion on admission CT angiography, in 13 participating centres. We calculated the relation per every 0.1 degrees Celsius increase in admission body temperature and recanalization at three days. Results Recanalization occurred in 80% of occluded arteries. There was no relation between body temperature and recanalization at three days after adjustments for age, NIHSS score on admission and treatment with alteplase (adjusted odds ratio per 0.1 degrees Celsius, 0.99; 95% confidence interval, 0.94-1.05; p = 0.70). Results for patients treated or not treated with alteplase were essentially the same. Conclusions Our findings suggest that in patients with acute ischaemic stroke there is no relation between body temperature on admission and recanalization of an occluded intracranial artery three days later, irrespective of treatment with alteplase

No Relation between Body Temperature and Arterial Recanalization at Three Days in Patients with Acute Ischaemic Stroke

Background Recanalization of an occluded intracranial artery is influenced by temperature-dependent enzymes, including alteplase. We assessed the relation between body temperature on admission and recanalization. Methods We included 278 patients with acute ischaemic stroke within nine hours after symptom onset, who had an intracranial arterial occlusion on admission CT angiography, in 13 participating centres. We calculated the relation per every 0.1 degrees Celsius increase in admission body temperature and recanalization at three days. Results Recanalization occurred in 80% of occluded arteries. There was no relation between body temperature and recanalization at three days after adjustments for age, NIHSS score on admission and treatment with alteplase (adjusted odds ratio per 0.1 degrees Celsius, 0.99; 95% confidence interval, 0.94-1.05; p = 0.70). Results for patients treated or not treated with alteplase were essentially the same. Conclusions Our findings suggest that in patients with acute ischaemic stroke there is no relation between body temperature on admission and recanalization of an occluded intracranial artery three days later, irrespective of treatment with alteplase