Computed Tomography Perfusion-based decision making for acute ischemic stroke: mismatch is the key
Submitted by: Dr Stefania Nannoni, Stroke Center, Department of Clinical Neurosciences, Lausanne University Hospital, Lausanne (Switzerland).
A 70-year-old woman with a past medical history significant for essential hypertension, and hyperlipidemia, was admitted to our institution for evaluation of left hemiparesis and dysarthria. Seven hours prior to hospital arrival, she suddenly fell while walking from her bedroom into the kitchen. She was unable to get up and contact the emergency service before her husband arrived. On admission, the neurological examination showed left facio-brachio-crural hemiparesis, dysarthria and left multimodal hemineglect (NIHSS = 11). She was normoglycemic and normotensive.
Cerebral computed tomography (CT) showed no intracranial hemorrhage and an ASPECTS of 9 in the right middle cerebral artery (MCA) territory. CT-angiography (CTA) revealed right proximal M1 occlusion. CT-perfusion (CTP) maps showed a small core volume (5 mL) and a large ischemic penumbra (100 mL), according to the published thresholds1 (Figure 1).
Given the patient’s time of onset of symptoms, no systemic thrombolysis was administered. In presence of both a purely radiological and clinico-radiological mismatch, the patient received an endovascular treatment, with an onset-to-groin puncture time of eight hours. Two passes of stent-retriever led to a complete recanalization of the first MCA segment.
During hospitalization, the patient experienced rapid improvement of her neurological deficits. A CT scan at 24 hours showed a small infarction in the right deep MCA territory. The stroke etiology was attributed to large-vessel disease. At 3 months follow-up visit she reported increased tiredness but was able to return to usual daily activities (modified Rankin Scale 1).
CTP imaging has a growing role in evaluating stroke. Its main clinical utility in the AIS setting is the identification and quantification the tissue viability at the time of patient presentation2. Through the differentiation of salvageable ischemic penumbra from core infarct, it may help identify patients most likely to benefit from acute revascularization therapies.
Appropriate imaging selection was proved useful in clinical decision making in patients with AIS, especially in the extended time window. Efficacy of late endovascular treatment, i.e. after 6 hours from symptoms onset, has recently been demonstrated in two RCTs (DAWN and DEFUSE-3) based on radiological selection of AIS patients with proximal anterior large vessel occlusion and with large mismatch between ischemic penumbra and the infarct core3-4. In light of these results, the new AHA/ASA stroke guidelines recommend thrombectomy in eligible patients 6 to 16 hours after a stroke (level 1A recommendation). On the basis of the DAWN results, the procedure is “reasonable” in patients 16 to 24 hours after a stroke (level IIa-B-R)5.
There are several possible definitions of “mismatch” that can be used in clinical practice. The DAWN trial enrolled patients having salvageable brain tissue on the basis of “clinical-core mismatch”, that is, patients who have a small core volume and a large clinical deficit (NIHSS ³10). This high NIHSS is associated to an extensive brain area that is clinically not functional, but still potentially salvageable. In the DEFUSE-3 trial, a pure radiological mismatch definition was used: patients underwent imaging with CTP or MRI diffusion/perfusion and an automated software program (RAPID©) was used to determine whether patients fulfilled the requirements for “target mismatch”. The trial required a mismatch ratio (the ratio of the volume of ischemic tissue on perfusion imaging to infarct volume) of at least 1.8 and a relatively small volume of core (in this case less than 70 mL).
These types of mismatch allow the quantification of the proportion of salvageable brain tissue and have to be distinguished from another type of mismatch, recently proven useful in the setting of unknown time of onset stroke. This is the MRI-based DWI/FLAIR mismatch, defined as an ischemic lesion visible on DWI without no parenchymal hyperintensity on FLAIR sequences. This finding indicated that the stroke had occurred approximately within the previous 4.5 hours and has been used for patients’ selection to systemic thrombolysis in the positive WAKE-UP trial6.
Although several issues regarding the first choice of acute neuroimaging remain unclear, the use of multimodal brain imaging in the acute phase of stroke should be encouraged in order to replace time clock with biological criteria.
- Wintermark M, Flanders AE, Velthuis B, et al. Perfusion-CT assessment of infarct core and penumbra: receiver operating characteristic curve analysis in 130 patients suspected of acute hemispheric stroke. Stroke. 2006;37(4):979-85.
- Donahuea J, Wintermark M. Perfusion CT and acute stroke imaging: Foundations, applications, and literature review. J Neurorad 2015;42:21—29.
- Nogueira RG, Jadhav AP, Haussen DC, et al. Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct. N Engl J Med 2018; 378(1): 11-21.
- Albers GW, Marks MP, Kemp S, et al. Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging. N Engl J Med 2018; 378(8): 708-718.
- Powers WJ, Rabinstein AA, Ackerson T, et al. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2018;49(3):e46-e110.
- Götz T, Simonsen CZ, Boutitie F, et al. for the WAKE-UP Investigators. MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset. N Engl J Med 2018; DOI: 10.1056/NEJMoa1804355.