Irene C. van der Schaaf

Perfusion-CT Assessment of Infarct Core and Penumbra: Receiver Operating Characteristic Curve Analysis in 130 Patients Suspected of Acute Hemispheric Stroke

Background and Purpose— Different definitions have been proposed to define the ischemic penumbra from perfusion-CT (PCT) data, based on parameters and thresholds tested only in small pilot studies. The purpose of this study was to perform a systematic evaluation of all PCT parameters (cerebral blood flow, volume [CBV], mean transit time [MTT], time-to-peak) in a large series of acute stroke patients, to determine which (combination of) parameters most accurately predicts infarct and penumbra. Methods— One hundred and thirty patients with symptoms suggesting hemispheric stroke ≤12 hours from onset were enrolled in a prospective multicenter trial. They all underwent admission PCT and follow-up diffusion-weighted imaging/fluid-attenuated inversion recovery (DWI/FLAIR); 25 patients also underwent admission DWI/FLAIR. PCT maps were assessed for absolute and relative reduced CBV, reduced cerebral blood flow, increased MTT, and increased time-to-peak. Receiver-operating characteristic curve analysis was performed to determine the most accurate PCT parameter, and the optimal threshold for each parameter, using DWI/FLAIR as the gold standard. Results— The PCT parameter that most accurately describes the tissue at risk of infarction in case of persistent arterial occlusion is the relative MTT (area under the curve=0.962), with an optimal threshold of 145%. The PCT parameter that most accurately describes the infarct core on admission is the absolute CBV (area under the curve=0.927), with an optimal threshold at 2.0 ml×100 g−1. Conclusion— In a large series of 130 patients, the optimal approach to define the infarct and the penumbra is a combined approach using 2 PCT parameters: relative MTT and absolute CBV, with dedicated thresholds.

Risk of Rupture of Unruptured Intracranial Aneurysms in Relation to Patient and Aneurysm Characteristics An Updated Meta-Analysis

Background and Purpose— We updated our previous review from 1996 on the risk of rupture of unruptured intracranial aneurysms, aiming to include the newly published articles. Methods— We reviewed all studies from our former meta-analysis and performed a Medline search for new studies published after 1996. We calculated overall risks of rupture for studies with a mean follow-up time of <5, 5 to 10, and >10 years. Relative risks (RR) were calculated by comparing the risk of rupture in patients with and without potential risk factors. We aimed to perform multivariable analyses of the different risk factors with meta-regression analysis. Results— We included 19 studies (10 new) with 4705 patients and 6556 unruptured aneurysms (follow-up 26 122 patient-years). The overall rupture risks were 1.2% (follow-up <5 years), 0.6% (follow-up 5 to 10 years), and 1.3% (follow-up >10 years). In the univariable analysis, statistically significant risk factors for rupture were age >60 years (RR 2.0; 95% confidence interval [CI], 1.1 to 3.7), female gender (RR 1.6; 95% CI, 1.1 to 2.4), Japanese or Finnish descent (RR 3.4; 95% CI, 2.6 to 4.4), size >5 mm (RR 2.3; 95% CI, 1.0 to 5.2), posterior circulation aneurysm (RR 2.5; 95% CI, 1.6 to 4.1), and symptomatic aneurysm (RR 4.4; 95% CI, 2.8 to 6.8). Meta-regression analysis yielded implausible results. Conclusions— Age, gender, population, size, site, and type of aneurysm should be considered in the decision whether to treat an unruptured aneurysm. Pooled multivariable analyses of individual data are needed to identify independent risk factors and to provide more reliable risk estimates for individual patients.

Effect of different components of triple-H therapy on cerebral perfusion in patients with aneurysmal subarachnoid haemorrhage: a systematic review.

IntroductionTriple-H therapy and its separate components (hypervolemia, hemodilution, and hypertension) aim to increase cerebral perfusion in subarachnoid haemorrhage (SAH) patients with delayed cerebral ischemia. We systematically reviewed the literature on the effect of triple-H components on cerebral perfusion in SAH patients.MethodsWe searched medical databases to identify all articles until October 2009 (except case reports) on treatment with triple-H components in SAH patients with evaluation of the treatment using cerebral blood flow (CBF in ml/100 g/min) measurement. We summarized study design, patient and intervention characteristics, and calculated differences in mean CBF before and after intervention.ResultsEleven studies (4 to 51 patients per study) were included (one randomized trial). Hemodilution did not change CBF. One of seven studies on hypervolemia showed statistically significant CBF increase compared to baseline; there was no comparable control group. Two of four studies applying hypertension and one of two applying triple-H showed significant CBF increase, none used a control group. The large heterogeneity in interventions and study populations prohibited meta-analyses.ConclusionsThere is no good evidence from controlled studies for a positive effect of triple-H or its separate components on CBF in SAH patients. In uncontrolled studies, hypertension seems to be more effective in increasing CBF than hemodilution or hypervolemia.

Venous Drainage in Perimesencephalic Hemorrhage

Background and Purpose— In perimesencephalic nonaneurysmal hemorrhage (PMH), subarachnoid blood accumulates around the midbrain. Clinical and radiological characteristics suggest a venous origin of PMH. We compared the venous drainage of the midbrain between patients with PMH and aneurysmal subarachnoid hemorrhage (aSAH) by means of computed tomography angiography (CTA). Methods— CTAs of 55 PMH patients and 42 aSAH patients with a posterior circulation aneurysm were reviewed. Venous drainage was classified into: (1) normal continuous: the basal vein of Rosenthal is continuous with the deep middle cerebral vein and drains mainly to the vein of Galen (VG); (2) normal discontinuous: drainage anterior to uncal veins and posterior to VG; and (3) primitive variant: drainage to other veins than VG. Additionally, we compared in PMH patients the side of the primitive variant and side of the bleeding. Results— A primitive variant was present on one or both hemispheres in 53% of PMH patients with PMH (95% CI, 40% to 65%) and in 19% of aSAH patients (95% CI, 10% to 33%). In all 16 PMH patients with a unilateral primitive drainage, blood was seen on the side of the primitive drainage (100%; 95% CI, 81% to 100%); blood was never found mainly on the side with normal drainage. Conclusions— Patients with PMH have a primitive venous drainage directly into dural sinuses instead of via the vein of Galen more often than do controls. Moreover, the side of the perimesencephalic hemorrhage relates to the side of the primitive drainage. These results further support a venous origin of PMH.

The spectrum of presentations of venous infarction caused by deep cerebral vein thrombosis.

The classic features of thrombosis of the deep cerebral venous system are severe dysfunction of the diencephalon, reflected by coma and disturbances of eye movements and pupillary reflexes, resulting in poor outcome. However, partial syndromes without a decrease in the level of consciousness or brainstem signs exist, which may lead to initial misdiagnoses. The spectrum of clinical symptoms reflects the degree of venous congestion, which depends not only on the extent of thrombosis in the deep veins but also on the territory of the involved vessels and the establishment of venous collaterals. For example, thrombosis of the internal cerebral veins with (partially) patent basal veins and sufficient collaterals may result in relatively mild symptoms. Deep cerebral venous system thrombosis is an underdiagnosed condition when symptoms are mild, even in the presence of a venous hemorrhagic congestion. Identification of venous obstruction has important therapeutic implications. The diagnosis should be strongly suspected if the patient is a young woman, if the lesion is within the basal ganglia or thalamus, and especially if it is bilateral.

Diagnosing Delayed Cerebral Ischemia With Different CT Modalities in Patients With Subarachnoid Hemorrhage With Clinical Deterioration

Background and Purpose— Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage worsens the prognosis and is difficult to diagnose. We investigated the diagnostic value of noncontrast CT (NCT), CT perfusion (CTP), and CT angiography (CTA) for DCI after clinical deterioration in patients with subarachnoid hemorrhage. Methods— We prospectively enrolled 42 patients with subarachnoid hemorrhage with clinical deterioration suspect for DCI (new focal deficit or Glasgow Coma Scale decrease ≥2 points) within 21 days after hemorrhage. All patients underwent NCT, CTP, and CTA scans on admission and directly after clinical deterioration. The gold standard was the clinical diagnosis DCI made retrospectively by 2 neurologists who interpreted all clinical data, except CTP and CTA, to rule out other causes for the deterioration. Radiologists interpreted NCT and CTP images for signs of ischemia (NCT) or hypoperfusion (CTP) not localized in the neurosurgical trajectory or around intracerebral hematomas, and CTA images for presence of vasospasm. Diagnostic values for DCI of NCT, CTP, and CTA were assessed by calculating sensitivities, specificities, positive predictive values, and negative predictive values with 95% CIs. Results— In 3 patients with clinical deterioration, imaging failed due to motion artifacts. Of the remaining 39 patients, 25 had DCI and 14 did not. NCT had a sensitivity of 0.56 (95% CI, 0.37 to 0.73), specificity=0.71 (0.57 to 0.77), positive predictive value=0.78 (0.55 to 0.91), negative predictive value=0.48 (0.28 to 0.68); CTP: sensitivity=0.84 (0.65 to 0.94), specificity=0.79 (0.52 to 0.92), positive predictive value=0.88 (0.69 to 0.96), negative predictive value=0.73 (0.48 to 0.89); CTA: sensitivity=0.64 (0.45 to 0.80), specificity=0.50 (0.27 to 0.73), positive predictive value=0.70 (0.49 to 0.84), negative predictive value=0.44 (0.23 to 0.67). Conclusion— As a diagnostic tool for DCI, qualitative assessment of CTP is overall superior to NCT and CTA and could be useful for fast decision-making and guiding treatment.

Difference in Aneurysm Characteristics Between Ruptured and Unruptured Aneurysms in Patients With Multiple Intracranial Aneurysms

Background and Purpose— Prediction of the risk of rupture of unruptured intracranial aneurysms is mainly based on aneurysm size and location. Previous studies identified features of aneurysm shape and flow angles as additional risk factors for aneurysm rupture, but these studies were at risk for confounding by patient-specific risk factors such as hypertension and age. In this study, we avoided this risk by comparing characteristics of ruptured and unruptured aneurysms in patients with both aneurysmal subarachnoid hemorrhage and multiple intracranial aneurysms. Methods— We included patients with aneurysmal subarachnoid hemorrhage and multiple aneurysms who presented to our hospital between 2003 and 2013. We identified the ruptured aneurysm based on bleeding pattern on head computed tomography or surgical findings. Aneurysm characteristics (size, location, shape, aspect ratio [neck-to-dome length / neck-width], flow angles, sidewall or bifurcation type, and contact with bone) were evaluated on computed tomographic angiograms. We calculated odds ratios with 95% confidence intervals with conditional univariable logistic regression analysis. Analyses were repeated after adjustment for aneurysm size and location. Results— The largest aneurysm had not ruptured in 36 (29%) of the 124 included patients with 302 aneurysms. Odds ratios for aspect ratio ≥1.3 was 3.3 (95% confidence intervals [1.3–8.4]) and odds ratios for irregular shape was 3.0 (95% confidence intervals [1.0–8.8]), both after adjustment for aneurysm size and location. Conclusions— Aspect ratio ≥1.3 and irregular shape are associated with aneurysm rupture independent of aneurysm size and location, and independent of patient characteristics. Additional studies need to assess to what extent these factors increase the risks of rupture of small aneurysms in absolute terms.

Diagnostic Threshold Values of Cerebral Perfusion Measured With Computed Tomography for Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage

Background and Purpose— Early diagnosis of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage is critical but difficult. We analyzed diagnostic threshold values of CT perfusion for use in detection of DCI in patients with subarachnoid hemorrhage. Methods— We prospectively enrolled patients with subarachnoid hemorrhage with CT perfusion on admission and at time of clinical deterioration or after 1 week if no deterioration occurred. The gold standard was the clinical diagnosis of DCI based on all clinical, laboratory, and imaging data except CT perfusion. Patients with failed imaging (n=6) and other causes of deterioration (n=45) were excluded for the current study. We measured CT perfusion values, including cerebral blood volume, blood flow, mean transit time (MTT), and time to peak in predefined regions of interest and then compared absolute perfusion and perfusion asymmetry for patients with and without DCI. Diagnostic threshold values for DCI were evaluated and sensitivity and specificity calculated for optimal thresholds. Results— Of 85 eligible patients with subarachnoid hemorrhage, 50 had DCI; 35 patients with no clinical deterioration comprised the reference group. Cerebral blood flow was significantly lower, MTT higher, and perfusion asymmetry larger in patients with DCI. We found that largest absolute MTT and the MTT difference between hemispheres were good diagnostic tests. Diagnostic threshold values with optimal sensitivity and specificity were an MTT of 5.9 seconds and an MTT difference of 1.1 second. Conclusion— Thresholds for absolute MTT values and between-hemisphere MTT differences on CT perfusion can distinguish between patients with delayed cerebral ischemia and clinically stable patients.

Histopathologic Composition of Cerebral Thrombi of Acute Stroke Patients Is Correlated with Stroke Subtype and Thrombus Attenuation

Introduction We related composition of cerebral thrombi to stroke subtype and attenuation on non-contrast CT (NCCT) to gain more insight in etiopathogenesis and to validate thrombus attenuation as a new imaging biomarker for acute stroke. Methods We histopathologically investigated 22 thrombi retrieved after mechanical thrombectomy in acute stroke patients. First, thrombi were classified as fresh, lytic or organized. Second, percentages of red blood cells (RBCs), platelets and fibrin and number of red, white (respectively RBCs or platelets outnumbering other components with ≥15%) or mixed thrombi were compared between large artery atherosclerosis (LAA), cardioembolism, dissection and unknown subtype. Third, correlation between attenuation and RBCs, platelets and fibrin was calculated using Pearsons correlation coefficients (r). Results Thrombi were fresh in 73% (n = 16), lytic in 18% (n = 4) and organized in 9% (n = 2). The stroke cause was LAA in eight (36%), cardioembolism in six (27%), dissection in three (14%), and unknown in five (23%) patients. LAA thrombi showed the highest percentage RBCs (median 50 (range 35–90)), followed by dissection (35 (20–40), p = 0.05), cardioembolism (35 (5–45), p = 0.013) and unknown subtype (25 (2–40), p = 0.006). No differences in platelets (p = 0.16) and fibrin (p = 0.52) between subtypes were found. LAA thrombi were classified as red or mixed (both n = 4), cardioembolisms as mixed (n = 5) or white (n = 1) and dissection as mixed (n = 3). There was a moderate positive correlation between attenuation and RBCs (r = 0.401, p = 0.049), and weak negative correlations with platelets (r = −0.368, p = 0.09) and fibrin (r = −0.073, p = 0.75). Conclusions The majority of cerebral thrombi is fresh. There are no differences in age of thrombi between subtypes. LAA thrombi have highest percentages RBCs, cardioembolism and unknown subtype lowest. No relationship exists between subtype and platelets or fibrin percentages. We found a correlation between the RBC-component and thrombus attenuation, which improves validation of thrombus attenuation on NCCT as an imaging biomarker for stroke management.

Yield of Short-Term Follow-up CT/MR Angiography for Small Aneurysms Detected at Screening

BACKGROUND AND PURPOSE Patients with a history of subarachnoid hemorrhage (SAH) or familial intracranial aneurysms (FIA) are at increased risk for aneurysm formation and rupture. Small aneurysms detected at screening may be left untreated and followed over time. The yield of follow-up CT/MR angiography (CTA/MRA) 1 or 2 years after detection to evaluate growth of these aneurysms is unknown. METHODS We prospectively followed patients with small aneurysms detected at screening at a 1-year interval using CTA or MRA. We assessed size, site, and number of the aneurysms and risk factors such as smoking, alcohol use, and hypertension. We evaluated the short-term growth and rupture rate and possible risk factors for growth and rupture. RESULTS Ninety-three patients (67 with a history of SAH, 16 with FIA, and 10 with a history of both SAH and FIA) with 125 aneurysms underwent CTA/MRA follow-up. Sixty-five patients were followed up once, and 28 patients were followed up twice (median follow-up time, 1.3 years). In 3 of the 93 patients (3.2%), an aneurysm enlarged slightly (0.5 to 1.5 mm). Two patients (2.2%) had a SAH: 1 from an aneurysm at the clip-site from a previous operation that ruptured without enlargement and the other from a newly developed dissecting aneurysm. The only statistically significant risk factor for growth and rupture was a history of both SAH and FIA (relative risk, 10.1; 95% CI, 1.3 to 81.9). CONCLUSIONS The yield of early follow-up of small aneurysms in patients with a history of SAH or FIA is small and does not eliminate the risk of rupture. Whether follow-up at intervals >1 year is useful requires further study.