BACKGROUND AND PURPOSE—Intracranial thrombi can be characterized according to their permeability as measured by contrast agent penetration. Thrombus composition and its associated pathogenesis are ...important factors affecting treatment and secondary prevention. We aimed to explore the histopathologic factors explaining the heterogeneity of thrombus permeability measures and evaluated potential correlations with stroke pathogenesis.
METHODS—Thrombus densities were measured in thin-slice noncontrast computed tomography and automatically aligned computed tomographic angiography images of 133 patients with large-vessel occlusions of the middle cerebral artery. Change in thrombus attenuation (Δt) and corrected void fraction (ε; attenuation increase corrected for contralateral artery densities) were calculated. First, these thrombus perviousness measures were correlated with histological thrombus components (especially fractions of fibrin-platelet accumulation and red blood cells) and stroke pathogenesis (n=32). For validation, an association between perviousness and pathogenesis was assessed in a second, independent cohort (n=101).
RESULTS—Thrombus perviousness estimates were correlated with both fibrin/platelets fractions (Δtr=0.43, P=0.016/εr=0.45, P=0.01) and inversely with red blood cells counts (Δtr=−0.46, P=0.01/εr=−0.49, P=0.006). In the first cohort, Δt was substantially higher in samples from patients with cardioembolic stroke pathogenesis as compared with noncardioembolic-derived thrombi (P=0.026). In the validation cohort, thrombus perviousness measures differed significantly between cardioembolic (Δtmedian interquartile range=12.53 8.70–17.90; εmedian interquartile range=0.054 0.036–0.082) and noncardioembolic thrombi (Δtmedian interquartile range=3.2 2.17–6.44, P<0.001; εmedian interquartile range=0.020 0.011–0.027, P<0.001) and were associated with pathogenesis (Δtβ=0.45, P=0.016/εβ=83.6, P=0.013) in a binary logistic regression model.
CONCLUSIONS—Permeable thrombi showed a strong correlation with lower fractions of red blood cells counts and more fibrin/platelets conglomerations, concurrent with an association with cardioembolic origin. This novel information about thrombus perviousness may be valuable as a new and simple to acquire imaging marker for identifying stroke pathogenesis using early and readily available imaging.
Premature-born infants have aberrant gyrification, but whether these changes persist into adulthood is unclear. Hedderich et al. reveal lasting changes in gyrification in adults who were born ...prematurely and link these structural changes to impaired cognitive performance.
Abstract
Gyrification is a hallmark of human brain development, starting in the second half of gestation in primary cortices, followed by unimodal and then transmodal associative cortices. Alterations in gyrification have been noted in premature-born newborns and children, suggesting abnormal cortical folding to be a permanent feature of prematurity. Furthermore, both gyrification and prematurity are tightly linked with cognitive performance, indicating a link between prematurity, gyrification, and cognitive performance. To investigate this triangular relation, we tested the following two hypotheses: (i) gyrification is aberrant in premature-born adults; and (ii) aberrant gyrification contributes to the impact of prematurity on adult cognitive performance. One hundred and one very premature-born adults (i.e. adults born before 32 weeks of gestation, and/or with birth weight <1500 g) and 111 mature-born adults were assessed by structural MRI and cognitive testing at 27 years of age. Gyrification was measured by local cortical absolute mean curvature (AMC), evaluated through structural MRI. Cognitive performance was assessed by the Wechsler Adult Intelligence Scale, full-scale IQ test. Two-sample t-tests, regression and mediation analyses were used to assess AMC group differences and the relation between AMC, birth-related variables, and full-scale IQ. Three key findings were identified. First, local AMC was widely increased in fronto-temporo-parietal primary and associative cortices of very premature-born adults. Increase of AMC was inversely associated with gestational age and birth weight and positively associated with medical complications at birth, respectively. Second, increased AMC of temporal associative cortices specifically contributed to the association between prematurity and reduced adult IQ (two-path mediation), indicating that aberrant gyrification of temporal associative cortices is critical for impaired cognitive performance after premature birth. Finally, further investigation of the relationship of gyrification between the early folding postcentral cortices and associative temporal cortices, folding later during neurodevelopment, revealed that the effect of gyrification abnormalities in associative temporal cortices on adult IQ is influenced itself by gyrification abnormalities occurring in the early folding postcentral cortices (three-path mediation). These results indicate that gyrification development across cortical areas in the brain conveys prematurity effects on adult IQ. Overall, these results provide evidence that premature birth leads to permanently aberrant gyrification patterns suggesting an altered neurodevelopmental trajectory. Statistical mediation modelling suggests that both aberrant gyrification itself as well as its propagation across the cortex express aspects of impaired neurodevelopment after premature birth and lead to reduced cognitive performance in adulthood. Thus, markers of gyrification appear as potential candidates for prognosis and treatment of prematurity effects.
Arterial spin labeling (ASL) is a non-invasive magnetic resonance imaging (MRI) method for the assessment of cerebral blood flow (CBF). This review summarizes recent ASL-based investigations in adult ...and pediatric patients with migraine with aura, migraine without aura, and chronic migraine. A systematic search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted within PubMed and reference sections of articles identified from April 2014 to November 2022. Out of 236 initial articles, 20 remained after filtering, encompassing data from 1155 subjects in total. Cross-sectional studies in adults showed inconsistent results, while longitudinal studies demonstrated that cerebral perfusion changes over the migraine cycle can be tracked using ASL. The most consistent findings were observed in ictal states among pediatric migraine patients, where studies showed hypoperfusion matching aura symptoms during early imaging followed by hyperperfusion. Overall, ASL is a useful but currently underutilized modality for evaluating cerebral perfusion in patients with migraine. The generalizability of results is currently limited by heterogeneities regarding study design and documentation of clinical variables (e.g., relation of attacks to scanning timepoint, migraine subtypes). Future MRI studies should consider augmenting imaging protocols with ASL to further elucidate perfusion dynamics in migraine.
Objectives
During mechanical recanalization of large vessel occlusions (LVO), the use of proximal flow arrest with balloon guide catheters (BGC) was shown to be associated with better angiographic ...and even clinical outcome. The aim of the study was to analyze the impact of BGC use on microstructural alterations in the salvaged penumbra.
Methods
All patients who underwent mechanical recanalization of LVO of the anterior circulation were reviewed within a prospective stroke registry of a single comprehensive stroke center. Fifty-two patients received an admission CT perfusion together with post-interventional diffusion tensor imaging. Technical details such as BGC usage were correlated with microstructural integrity changes of the salvaged gray matter through the mean diffusivity (MD) index. Moderation analysis was performed to test the interaction of BGC on the correlation between angiographic and clinical outcomes.
Results
For all patients with complete reperfusion, microstructural integrity changes with lowered MD index were found within the salvaged penumbra for cases of non-BGC usage (mean − 0.02) compared to cases with BGC usage (0.01,
p
= 0.04). The importance of complete reperfusion for good clinical outcome is predominantly based on patients treated with BGC (effect 2.78,
p
= 0.01 vs. for non-BGC: 0.3,
p
= 0.71).
Conclusions
The lowered MD index early after mechanical recanalization without BGC usage can be interpreted as microstructural ischemic damage of the salvaged penumbra. It was shown that achieving complete reperfusion in a setting of BGC usage with proximal flow arrest minimizes penumbral damage and improves long-term outcomes.
Key Points
• Microstructural ischemic damage can be reduced by using proximal flow arrest during endovascular treatment with balloon guide catheter
.
• Complete reperfusion in a setting of balloon guide catheter minimizes penumbral damage and improves long-term outcome
.
BackgroundEndovascular therapy for acute ischemic stroke has been shown to be highly effective in selected patients. However, the ideal criteria for patient selection are still debated. It is well ...known that collateral flow is an important factor, but the assessment is often subjective and time-consuming. Relative cerebral blood volume (rCBV) is a putative indicator of collateral capacity and can be quickly and easily determined by automated quantitative analysis. We investigated the relationship between rCBV of the affected region and clinical outcome in patients with acute ischemic stroke after endovascular therapy.MethodsWe conducted a retrospective study on consecutive patients between January 2017 and May 2019. Patients with acute ischemic stroke of the anterior circulation who underwent imaging including computed tomography perfusion and were treated with mechanical thrombectomy (MT) were eligible for inclusion. rCBV was calculated automatically with RAPID software by dividing the average cerebral blood volume (CBV) of the affected region (time-to-maximum (Tmax) > 6 s) by the CBV of the unaffected contralateral side. The primary outcome was determined by the modified Rankin Scale (mRS) after 90 days. Good clinical outcome was defined as mRS ≤ 2. We compared means, performed mono- and multivariate logistical regression and calculated a receiver operating characteristic (ROC)-analysis to determine the ideal cutoff value to predict clinical outcomes.Results155 patients were enrolled in this study. 66 patients (42.58%) had good clinical outcomes. Higher rCBV was associated with good clinical outcome (p < 0.001), even after adjustment for the patients’ status according to mRS and National Institute of Health Stroke Scale (NIHSS) age and Alberta stroke program early computed tomography score (ASPECTS) at baseline (p = 0.006). ROC-analysis revealed 0.650 (confidence interval: 0.616–0.778) as the optimal cutoff value.ConclusionHigher rCBV at baseline is associated with good clinical long-term outcomes in patients with acute ischemic stroke treated by MT. In this study we provide the biggest collective so far that gives evidence that rCBV can be a valuable tool to identify patients who might benefit from MT and are able give a threshold to help to offer patients MT in borderline cases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BACKGROUND AND PURPOSE—Recent studies show that mechanical thrombectomy of acute basilar artery occlusions (BAO) results in high rates of successful recanalization and good outcomes, but predictors ...are not completely established yet. Varying occlusion types may benefit differently, and especially, an underlying basilar stenosis (BS) seems to have an impact. Aim of this study was to investigate angiographic and clinical differences in BAO subtypes and to test the potential of perviousness measures for a preinterventional identification of clinically relevant different occlusion types.
METHODS—All consecutive patients with acute BAO, endovascular treated at a single comprehensive stroke center, were included. Different occlusion patterns, especially underlying BS, were identified and analyzed in respect of angiographic and clinical (National Institutes of Health Stroke Scale/modified Rankin Scale) outcome parameters (N=115). Thrombus perviousness measures (change in thrombus attenuation Δt and corrected void fraction ε) were assessed in admission computed tomography imaging and correlated to different etiological subgroups.
RESULTS—Despite comparable rates of successful recanalization (87% for BAO with BS versus 95% without BS), the BS group showed worse clinical outcome with higher National Institutes of Health Stroke Scale/modified Rankin Scale values (P=0.002/0.003). The group of BS turned out to have lower thrombus density values in unenhanced scans (mean, 42.0 Hounsfield units) and higher perviousness measures Δt (mean, 34.6 Hounsfield units) and ε (mean, 0.23) than thrombi without an underlying BS (mean, 53.6 Hounsfield units/13.1 Hounsfield units/0.08, P=0.01/ 0.004/ 0.001).
CONCLUSIONS—In agreement with previous studies, outcome of mechanical thrombectomy of BAO seems to depend on pathogenesis with less clinical benefit for underlying BS, raising the question of early identification of this subgroup. Perviousness showed a high potential to differentiate acute BAO with and without BS, possibly usable as an admission imaging marker for BS.
Although a pathophysiological impact remains difficult to prove in individual patient care, a patent foramen ovale (PFO) is currently considered of high relevance for secondary prophylaxis in ...selected patients with cryptogenic ischemic stroke. By quantification of histological clot composition, we aimed to enhance pathophysiological understanding of PFO attributable ischemic strokes. Retrospectively, we evaluated all cerebral clots retrieved by mechanical thrombectomy for acute ischemic stroke treatment between 2011 and 2021 at our comprehensive stroke care center. Inclusion criteria applied were cryptogenic stroke, age (≤60 years), and PFO status according to transesophageal echocardiography, resulting in a study population of 58 patients. Relative clot composition was calculated using orbit image analysis to define the ratio of main histologic components (fibrin/platelets (F/P), red blood cell count (RBC), leukocytes). Cryptogenic stroke patients with PFO (PFO+, n = 20) displayed a significantly higher percentage of RBC (0.57 ± 0.17; p = 0.002) and lower percentage of F/P (0.38 ± 0.15; p = 0.003) compared to patients without PFO (PFO–, n = 38) (RBC: 0.41 ± 0.21; F/P: 0.52 ± 0.20). In conclusion, histologic clot composition in cryptogenic stroke varies depending on the presence of a PFO. Our findings histologically support the concept that a PFO may be of pathophysiological relevance in cryptogenic ischemic stroke.
Abstract
Several observations suggest an impact of prematurity on the claustrum. First, the claustrum’s development appears to depend on transient subplate neurons of intra-uterine brain development, ...which are affected by prematurity. Second, the claustrum is the most densely connected region of the mammalian forebrain relative to its volume; due to its effect on pre-oligodendrocytes, prematurity impacts white matter connections and thereby the development of sources and targets of such connections, potentially including the claustrum. Third, due to its high connection degree, the claustrum contributes to general cognitive functioning (e.g., selective attention and task switching/maintaining); general cognitive functioning, however, is at risk in prematurity. Thus, we hypothesized altered claustrum structure after premature birth, with these alterations being associated with impaired general cognitive performance in premature born persons.
Using T1-weighted and diffusion-weighted magnetic resonance imaging in 70 very preterm/very low-birth-weight (VP/VLBW) born adults and 87 term-born adults, we found specifically increased mean diffusivity in the claustrum of VP/VLBW adults, associated both with low birth weight and at-trend with reduced IQ.
This result demonstrates altered claustrum microstructure after premature birth. Data suggest aberrant claustrum development, which is potentially related with aberrant subplate neuron and forebrain connection development of prematurity.
Premature birth is associated with alterations in brain structure, particularly in white matter. Among white matter, alterations in cortico-thalamic connections are present in premature-born infants, ...and they have been suggested both to last until adulthood and to contribute to impaired cognitive functions. To test these hypotheses, 70 very premature-born adults and 67 full-term controls underwent cognitive testing and diffusion-weighted imaging. Each cortical hemisphere was parcellated into six lobes, from which probabilistic tractography was performed to the thalamus. Connection probability was chosen as metric of structural connectivity. We found increased cortico-thalamic connection probability between left prefrontal cortices and left medio-dorsal thalamus and reduced connection probability between bilateral temporal cortices and bilateral anterior thalami in very premature-born adults. Aberrant prefronto- and temporo-thalamic connection probabilities were correlated with birth weight and days on ventilation, respectively, supporting the suggestion that these connectivity changes relate with the degree of prematurity. Moreover, an increase in left prefronto-thalamic connection probability also correlated with lower verbal comprehension index indicating its relevance for verbal cognition. Together, our results demonstrate that cortico-thalamic structural connectivity is aberrant in premature-born adults, with these changes being linked with impairments in verbal cognitive abilities. Due to corresponding findings in infants, data suggest aberrant development of cortico-thalamic connectivity after premature birth with lasting effects into adulthood.
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