By Firas Al-Ali
The PROACT II trial had 42% good clinical outcome (mRS 0–2) following pharmacological intervention only and established two key criteria for good outcome: arterial recanalisation and time from ictus. Since then, several mechanical devices have been invented and tried alone or in association with thrombolysis after the three-hour time frame showing significant improvement in speed and percentage of revascularisation (up to 90%), but the clinical improvement rate has remained almost unchanged at less than 50%, what we call “the 50% barrier.”
Obviously, a change in the way we treat and select these patients is in order. Multiple existing parameters are now being used to select patients for treatment, each with its own limitations. Time from symptom onset is an arbitrary criterion for patient selection because, depending on the collateral blood supply, the residual cerebral blood flow varies from patient to patient, and, therefore, time between occlusion and irreversible tissue damage is different for each patient. NIHSS is a clinical test and provides information about tissue function rather than structure; it reflects the percentage of tissue that is hypoperfused (i.e., clinically symptomatic, below the ischaemic threshold: 20–23ml/100g/min) but cannot differentiate reversibly from irreversibly damaged cerebral tissue. To date, no clear threshold has yet been determined to use NIHSS in patient selection for treatment.
Some studies have shown that ASPECTS on pre-intervention CT-scan correlated with clinical outcome, but others have shown no correlation. Since time is needed for irreversibly damaged tissue to be apparent on CT-scan, we expect to see some patients with poor outcome despite a favourable ASPECTS (≥7) on initial CT-scan. Ischaemic penumbra, as seen on MRI or CT perfusion images, has not yet been proven useful in any clinical trials.
To improve patient selection, we devised the Capillary Index Score (CIS), which reflects the percentage of viable tissue in the ischaemic area by demonstrating a fine and homogenous capillary blush on pre-intervention catheter cerebral angiography. To calculate the CIS, the ischaemic area is divided into three equal parts and each part is given a score of one if normal capillary blush is present or zero if no capillary blush appears. The scores for each of the three parts are then summed to determine the CIS for the ischaemic area. Zero or one is considered poor and two or three is considered favourable. In the Borgess acute ischaemic stroke registry, no patients who presented with poor CIS had good clinical outcome while 55% of all patients presenting with favourable CIS had good clinical outcome. In patients with favourable CIS and TIMI 3 revascularisation, the rate of good clinical outcome reached 83%. Interestingly, time from ictus in our series was not, in itself, a determining factor. Good outcome was found even when recanalisation occurred six to nine hours post-ictus in patients with favourable CIS, while patients with poor CIS had poor clinical outcome despite achieving a timely revascularisation within the six-hour window.
A change in the ischaemic stroke treatment algorithm is needed in order to break the 50% barrier. Although intravenous ischaemic stroke treatment has never been shown to exceed 35% good outcome and its recanalisation rate has never been higher than 45%, it is still standard practice. Its reliance on an arbitrary time window, without regard for the potential collateral blood supply of each individual patient, and its low recanalisation rate explain its lower success rate. On the other hand, the intra-arterial approach has a much higher recanalisation rate and allows us to calculate the CIS for each patient just before treatment, enabling us to use more accurate and rational patient selection criteria. Furthermore, if we offer intra-arterial treatment sooner, before the arbitrary three-hour window, we expect to find more patients with favourable CIS, before the cerebral tissue becomes irreversibly damaged. This should translate to better rates of good clinical outcome.
We believe that the time has come to change the acute ischaemic stroke treatment algorithm. Adding CIS to NIHSS and ASPECTS may improve patient selection, and by offering intra-arterial ischaemic stroke treatment as early as possible to patients with favourable CIS (even before the standard three-hour window), we may be able to break the 50% barrier. A large, prospective, multicentre study is in order.
Firas Al-Ali is director of Neurointerventional Surgery and Diagnostic Services, Borgess Medical Center, Kalamazoo, USA