Early CT signs in patients with acute middle cerebral artery occlusion: incidence of contrast staining and haemorrhagic transformations after intra-arterial reperfusion therapy

doi:10.1016/j.crad.2005.08.016

Clinical Radiology

Volume 61, Issue 2, February 2006, Pages 156-162

https://doi.org/10.1016/j.crad.2005.08.016 Get rights and content

AIM

To investigate how often early computed tomography (CT) signs are associated with blood–brain barrier (BBB) disruption and result in haemorrhagic transformations.

MATERIALS AND METHODS

Serial CT findings were prospectively evaluated in 61 patients with acute middle cerebral artery (MCA) occlusion who underwent initial CT examination within 3 h of stroke onset and who were treated with intra-arterial reperfusion therapy within 6 h of stroke onset. Obscuration of the margin of the lentiform nucleus and loss of the insular ribbon were evaluated as early CT signs in the deep MCA territories. Cortical effacement was also evaluated. BBB disruption was defined as contrast medium staining in post-therapeutic CT just after reperfusion therapy. The relationship between pre-therapeutic early CT signs and post-therapeutic contrast staining or haemorrhagic transformations was investigated.

RESULTS

The frequency of early CT signs in the deep MCA territories was significantly higher than that of cortical effacement (68.9 versus 27.9%). There were significant correlations between pre-therapeutic early CT signs and post-therapeutic contrast staining in both the deep and superficial MCA territories. Compared with early CT signs in the deep MCA territories, cortical effacement had a significantly higher incidence of post-therapeutic contrast staining (54.8 versus 82.4%). Although not statistically significant, cortical effacement tended to develop into haemorrhagic transformations. There was no correlation between early CT signs in the deep MCA territories and haemorrhagic transformations.

CONCLUSION

Cortical effacement may be an advanced CT sign with BBB disruption and potential risk for haemorrhagic transformations. The presence of early CT signs in the deep MCA territories may not be a contraindication of reperfusion therapy.

Section snippets

Patient selection

Since 1993, we have performed reperfusion therapies in 140 patients with acute MCA occlusion. Sixty-nine of these 140 patients underwent an initial CT examination within 3 h after onset of symptoms, eight of them were treated with intravenous administration of native tissue plasminogen activator (t-PA, tisokinase) for M2 occlusion. The other 61 patients were treated with intra-arterial reperfusion therapies that were completed within 6 h after symptom onset and were selected for this study.

Results

The initial CT study was performed within 30 min to 3 h (103±47 min, mean±standard deviation) after symptom onset. An initial CT examination was performed during the first hour after onset in 18 patients (29.5%), during the second hour in 18 (29.5%) and during the third hour in 25 (41.0%). There were 34 men and 27 women, 47–87 years old, with a mean age of 70.2±9.8 years (mean±standard deviation). Pre-therapeutic early CT signs, post-therapeutic contrast staining, and haemorrhagic transformations

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After endovascular therapy (EVT) for ischemic stroke, post-EVT CT imaging often shows areas of contrast extravasation (CE) caused by blood brain barrier disruption (BBBD). Before EVT, CT-perfusion (CTP) can be used to estimate salvageable tissue (penumbra) and irrevocably damaged infarction (core). In this study, we aimed to correlate CTP deficits to CE, as a surrogate marker for BBBD, after EVT for ischemic stroke.
In this single center study, EVT patients between 2010 and 2020 in whom both CTP at baseline and DECT post-EVT was performed were included. The presence of core and penumbra on CTP was assessed per ASPECTS region, resulting in a CTP-ASPECTS_core and a CTP-ASPECTS_{core+penumbra}. Likewise, CE on DECT was scored per ASPECTS region, resulting in a CE-ASPECTS. Correlation was assessed using Kendall’s tau correlation and positive predictive values (PPV) were calculated per ASPECTS region. Bland-Altman plots were created to visualize the agreement between the two scores.
194 patients met our inclusion criteria. The median core and penumbra were 8 cc (IQR 1–25) and 103 cc (IQR 68–141), respectively. The median CTP-ASPECTS_core, CTP-ASPECTS_{core+penumbra}, and CE-ASPECTS were 7 (IQR 4–9), 3 (IQR 1–4), and 6 (IQR 4–9), respectively. The correlation between CTP-ASPECTS_core and CE-ASPECTS was τ = 0.21, P <.001, and τ = 0.13, P =.02 between CTP-ASPECTS_{core+penumbra} and CE-ASPECTS. Bland-Altman plots showed a mean difference (CTP-ASPECTS minus CE-ASPECTS) of 0.27 (95 %CI −6.7–7.2) for CTP-ASPECTS_core and −3.2 (95 %CI −9.7–3.2) for CTP-ASPECTS_{core+penumbra}. The PPVs of the CTP-ASPECTS_core and CTP-ASPECTS_{core+penumbra} were highest for the basal ganglia.
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Associations between early ischemic signs on non-contrast CT and time since acute ischemic stroke onset: A scoping review
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Citation Excerpt :
The prevalence varied between studies. On a short timescale, the prevalence increased in all studies (Fig. 6A) [17,18,22,48,92]. On a long timescale, the prevalence did not consistently increase or decrease (Fig. 6B) [20,58,76].
Onset to imaging (OTI) time is a crucial factor in determining treatment eligibility for acute ischemic stroke patients, since the treatments are time-dependent. Patients with an unknown OTI time are often excluded from treatment, or advanced imaging is needed, which is not widely and readily available. As non-contrast CT (NCCT) is part of the standard stroke protocol, estimating OTI time using only NCCT would be valuable for patients with an unknown OTI time. Early ischemic signs (EISs) visible on NCCT might be fit for this purpose if an association between these signs and OTI time exists. This scoping review aims to provide an overview of the literature that associated OTI time with qualitative or quantitative EISs, including the hyperdense artery sign (HAS), decrease in grey matter-white matter differentiation, hypodensity, and mass effect.
The prevalence of the EISs at specific OTI times is assessed, and previously presented associations between the EISs and OTI time are reported.
The EIS prevalence varied between the studies. The HAS prevalence decreased after 6 h since onset. The hypodensity prevalence increased with increasing OTI time. Studies quantifying the extent of hypodensity could distinguish patients within and beyond treatment time windows, indicating its potential to estimate OTI time. Finally, mass effect prevalence was seen more often at later OTI times.
It is concluded that, despite the high prevalence variability between studies, some associations between EISs and OTI time can be observed. These are potentially valuable in estimating OTI time and supporting treatment decisions.
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Areas of infarction will often enhance (contrast staining) due to associated breakdown of the blood–brain barrier and the relatively large volumes of cervical and intracranially injected IA contrast. One study found that 55% of pretreatment basal ganglia infarcts demonstrated contrast staining after IA intervention and approximately a third of these went on to hemorrhagic transformation, whereas none of the lesions without contrast staining evolved to hemorrhage.25 It is difficult to distinguish contrast staining from petechial hemorrhage on regular NCCT, as both tend to “paint in” an infarct with hyperdensity and without significant mass effect (Fig. 7).
Although the non-contrast computed tomography head continues as the sole mandatory imaging technique before intravenous thrombolysis, the increased availability of advanced infarct/penumbral imaging techniques and confidence in their use have led many to adopt them into routine practice—most particularly before intra-arterial interventions. Computed tomography versus magnetic resonance-based routes to imaging the cerebral vasculature, cell death, and parenchymal perfusion have differing advantages in terms of speed, availability, exposures to contrast and radiation, sensitivity, and resolution. Continued refinement and future developments, such as the ability to quantitate perfusion, promise to lead to tailored treatment protocols that respect the individual variations in anatomy, physiology, and pathology. This should lead both to an extension of treatment to patients currently excluded by rigid time windows and the avoidance of futile therapies and their associated morbidities.
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Likewise, a small percentage of vessels in our study (10%) exhibited edema of the tunica media (Fig. 7). Nakano et al. (2006) noted the passage of intravascular computed tomography contrast material across the blood-brain barrier in humans within 20 min after the onset of ischemic stroke, without observable hemorrhage. Thus vascular ischemia is associated with a limited leaky endothelium (Dauber et al. 1985, 1990; Menon et al. 2004).
Ultrasound is known to enhance recombinant tissue plasminogen activator (rt-PA) thrombolysis. In this study, occlusive porcine whole blood clots were placed in flowing plasma within living porcine carotid arteries. Ultrasonically induced stable cavitation was investigated as an adjuvant to rt-PA thrombolysis. Aged, retracted clots were exposed to plasma alone, plasma containing rt-PA (7.1 ± 3.8 μg/mL) or plasma with rt-PA and Definity^® ultrasound contrast agent (0.79 ± 0.47 μL/mL) with and without 120-kHz continuous wave ultrasound at a peak-to-peak pressure amplitude of 0.44 MPa. An insonation scheme was formulated to promote and maximize stable cavitation activity by incorporating ultrasound quiescent periods that allowed for the inflow of Definity^®-rich plasma. Cavitation was measured with a passive acoustic detector throughout thrombolytic treatment. Thrombolytic efficacy was measured by comparing clot mass before and after treatment. Average mass loss for clots exposed to rt-PA and Definity^® without ultrasound (n = 7) was 34%, and with ultrasound (n = 6) was 83%, which constituted a significant difference (p < 0.0001). Without Definity^® there was no thrombolytic enhancement by ultrasound exposure alone at this pressure amplitude (n = 5, p < 0.0001). In the low-oxygen environment of the ischemic artery, significant loss of endothelium occurred but no correlation was observed between arterial tissue damage and treatment type. Acoustic stable cavitation nucleated by an infusion of Definity^® enhances rt-PA thrombolysis without apparent treatment-related damage in this ex vivo porcine carotid artery model.
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Other early CT signs of acute cerebral ischemia include subtle parenchymal hypodensities involving gray matter structures, such as the basal ganglia (loss of margins of the lentiform nucleus), cerebral cortex with sulcal effacement resulting from cytotoxic edema, and the so-called “loss of the insular ribbon sign” [7]. The incidence of these early CT changes ranges from 53% to 92% within the first 3 hours after onset of stroke symptoms and up to 100% after 6 hours [7,8]. The size of the hypodensity correlates with mortality.

View all citing articles on Scopus

View full text

Early CT signs in patients with acute middle cerebral artery occlusion: incidence of contrast staining and haemorrhagic transformations after intra-arterial reperfusion therapy

AIM

MATERIALS AND METHODS

RESULTS

CONCLUSION

Section snippets

Patient selection

Results

Lancet

PROACT: a phase II trial of recombinant pro-urokinase by direct arterial delivery in acute middle cerebral artery stroke

Stroke

Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial

JAMA

Sensitivity and prognostic value of early CT in occlusion of the middle cerebral artery trunk

AJNR Am J Neuroradiol

Correlation of early CT signs in the deep middle cerebral artery territories with angiographically confirmed site of arterial occlusion

AJNR Am J Neuroradiol

Diagnosis of acute cerebral infarction: comparison of CT and MR imaging

AJNR Am J Neuroradiol

Early computed tomographic findings for thrombolytic therapy in patients with acute brain embolism

Stroke

Neuroradiologic evaluation of patients with acute stroke treated with recombinant tissue plasminogen activator

AJNR Am J Neuroradiol

Hemorrhagic transformation of brain infarct: predictability in the first 5 hours from stroke onset and influence on clinical outcome

Neurology

Prediction of hemorrhagic complications after thrombolytic therapy for middle cerebral artery occlusion: value of pre- and post-therapeutic computed tomographic findings and angiographic occlusive site

Neurosurgery

Hemorrhagic transformation in acute ischemic stroke: potential contributing factors in the European Cooperative Acute Stroke Study

Stroke