Following carotid intervention, the number of detectable diffusion-weight magnetic resonance imaging (DWMRI) lesions is an order of magnitude greater than adverse clinical event (stroke/death). This lends credence to the use of DWMRI as a surrogate endpoint allowing comparisons of interventional strategies in studies with reduced sample size.
The International Carotid Stenting Study (ICSS) sub-study comparing DWMRI lesions in patients undergoing largely filter-protected carotid stenting and carotid endarterectomy demonstrated significantly fewer DWMRI lesions after carotid endarterectomy, implying superior of control of procedural microemboli. Sixty-two of 124 (50%) patients undergoing distal filter-protected transfemoral carotid artery stenting and 18 of 107 patients undergoing carotid endarterectomy (17%) had new DWMRI lesions (p<0.0001). Individual lesions were smaller in the carotid artery stenting group than in the carotid endarterectomy group (p<0.0001). Of the DWMRI positive scans following carotid artery stenting, 25 (34%) resulted from unprotected carotid artery stenting and 37 (75%) resulted from filter-protected carotid artery stenting (p<0.019). Total lesion volume per patient did not differ significantly between patients undergoing carotid artery stenting and those undergoing carotid endarterectomy.
Two small randomised trials compared proximal embolic protection (Medtronic MoMa) with distal filters during carotid artery stenting. There were substantial or significant reductions in DWMRI lesions for the MoMa compared with filter protection.
There were significantly fewer DWMRI lesions in the MoMa group ipsilateral to the carotid lesion (p<0.0002) but no difference in the DWMRI lesions in the contralateral hemisphere, implying the embolic penalty associated with catheterisation of the arch/great vessel origins for transfemoral carotid artery stenting. There was also a significant difference in favour of the MoMa system for lesion volume 0 [0 to 0.84] vs. 0.47 [0 to 2.4cm3] (p<0.0001).
The PROOF first-in-man analysis of high flow rate flow reversal via direct common carotid artery access (MICHI System) evaluated 65 patients, 48 of who had pre- and post-carotid artery stenting DWMRI read by two independent US neuroradiologists. Eight of 48 patients had new DWMRI lesions (16.7%).
Another study examined patients undergoing transcervical carotid artery stenting with flow reversal or distal filter-protected transfemoral carotid artery stenting. DWMRI lesions were found in four of 64 transcervical (12.9%) and in 11 transfemoral (33.3%) patients (p=0.03). In multivariate analysis, age (relative risk, 1.022; p<.001), symptomatic status (relative risk, 4.109; p<.001), and open-cell vs. closed-cell stent design (relative risk, 2.01; p<.001) were associated with a higher risk of lesions in the transfemoral group but not in the transcervical group.
The low rates of DWMRI lesions in studies of carotid artery stenting with flow reversal via direct carotid access are commensurate with carotid endarterectomy, presumably resulting from more effective embolic control and avoidance of catheterisation of the arch.
A prospective study of 110 patients undergoing filter-protected transfemoral carotid artery stenting investigated the fate of silent DWMRI lesions. Twelve of 30 DWI lesions persisted, resulting in a lesion reversibility rate of 60%. Seventy-five per cent (12/16) of the cortical lesions disappeared while only 30% (3/10) of subcortical lesions disappeared. Eighty-three per cent (14/17) of lesions measuring 0–5mm disappeared while only 31% (4/13) of lesions measuring >5mm disappeared. It was concluded that a large number of silent ischaemic lesions visualised on the DWI images post-carotid artery stenting disappear within months and therefore the extent of permanent carotid artery stenting-related cerebral damage may be overestimated.
The most recent analyses of the ICSS sub study data set revealed that patients in the carotid artery stenting group had more acute (relative risk 8.8, 95% CI 4.4-17.5, p<0.001) and persisting lesions (relative risk 4.2, 1.6-11.1; p=0.005) than patients in the carotid endarterectomy group. However, the rate of conversion from acute to persisting lesions was lower in the carotid artery stenting group than in the carotid endarterectomy group (RR 0.4, 0.2-0.8; p=0.007).
Systematic reviews have failed to provide consistent data across included studies comparing cognitive outcomes following carotid artery stenting and carotid endarterectomy.
Of 1,713 patients included in the ICSS, 140 of 177 patients enrolled in two Dutch centres had neuropsychometric testing at baseline and 120 at follow-up. Ten domains were examined, including executive function. There were no significant difference in overall cognition between patients undergoing carotid artery stenting and carotid endarterectomy despite the impressive difference in DWMRI lesions counts between carotid artery stenting and carotid endarterectomy.
“Standard” filter-protected transfemoral carotid artery stenting generates more DWMRI lesions than carotid endarterectomy but technical modifications (proximal embolic protection, direct carotid access) allow carotid artery stenting to more effectively compete where microemboli are concerned. Clinical correlation, with regards cognitive function is poor, implying either that a large number of DWI lesions are clinically irrelevant or that neuropsychometry is a blunt tool. DWMRI is a reasonable secondary endpoint for carotid interventions, but without watertight clinical inference, the use of DWMRI as a primary endpoint remains an unproven convenience.
Sumaira Macdonald is an interventional radiologist at Freeman Hospital, Newcastle, UK