SAN DIEGO—Although a large percentage of patients with carotid stenotic disease experience cognitive dysfunction following carotid endarterectomy or stenting, many patients show improvement in cognitive function in the months following these procedures, reported E. Sander Connolly Jr., MD, Associate Professor of Neurological Surgery and Director of the Cerebrovascular Research Laboratory at the Columbia University Neurological Institute in New York City.
“There has been some debate about the incidence of cognitive changes following carotid revascularization and whether or not they exist at all,” said Dr. Connolly at the 2009 International Stroke Conference. “In terms of neuropsychologic or cognitive function after carotid procedures, most of the debate circles around what tests you’re doing, how the test is administered, and at what time points the test is being administered.”
Measuring Changes in Cognitive Functioning
According to Dr. Connolly, cognitive function can be easily assessed with strong interobserver reliability using the following battery of tests: Boston naming, Controlled Oral Word Association, Halstead-Reitan Trails A and B, and Rey Complex Figure. “It’s very important to figure out what a true and meaningful change in these tests is from pre- to postoperative,” he commented. The best way to do that, he said, is to calculate standard deviation of change scores for control groups.
Using this method, Dr. Connolly, in collaboration with Eric Heyer, MD, and colleagues, has demonstrated in a range of studies that the incidence of cognitive dysfunction following carotid endarterectomy or stenting is approximately 25%. In addition, they found that cognitive dysfunction in patients with carotid stenotic disease is associated with elevated serum S100B levels, a marker of glial injury. “So we were fairly confident that this injury in the patients that we were calling injured was real,” said Dr. Connolly.
Further analyses accounting for regional versus general anesthetic and different backgrounds of surgeons (eg, vascular surgeons vs neurosurgeons) also demonstrated a 25% incidence of cognitive dysfunction in these patients.
But does improvement in cognitive dysfunction also occur in patients who are undergoing carotid endarterectomy or stenting? “The answer to this,” said Dr. Connolly, “is definitely ‘yes.’” With respect to patients undergoing endarterectomy, “it appears that patients who have a preoperative blood flow perfusion deficit related to the vessel of interest that is being revascularized actually tend to improve in cognitive function at 24 hours compared to those [who] don’t,” he said.
In addition, a recent study showed that as many as 45% of 71 patients improved on two tests when assessed six months post–carotid stenting. “What was interesting was that it really correlated with the degree of angiographic evidence of flow abnormalities,” said Dr. Connolly. The incidence of cognitive improvement was high in patients who did not have an A1 filling. After stenting, the A1 filled and improved blood flow in that hemisphere, he explained.
“I think the take-home message is that while injury is common, improvements are also common after these procedures,” Dr. Connolly commented.
Mechanisms of Cognitive Injury Following Revascularization
Two possible mechanisms for cognitive injury after revascularization that have been proposed include a regional hypo- or hyperperfusion or microembolization. For patients undergoing carotid endarterectomy, the former may be a better explanation, whereas for patients undergoing stenting, microemboli may play a role.
Evidence suggests that among patients who have had an endarterectomy, cognitive dysfunction is diffusion-weighted imaging (DWI)-independent. In one study involving patients undergoing endarterectomy, Dr. Connolly and colleagues noted little correlation between those patients who had cognitive injury and small DWI hits.
“You had patients with small hits who had no cognitive injury, and you had people with no hits and cognitive injury,” he said. “So we felt that it’s probably not related to a large degree of microembolization.” Dr. Connolly also found that among patients who had both transcranial Doppler ultrasound monitoring and compressed spectral array EEG during their procedures, “if the cross clamp showed a good cortical EEG but poor blood flow in the M1 segment, that those patients had a much higher rate of cognitive dysfunction, leading us to believe that regional hyperperfusion may be playing a role.”
In MR profusion studies with both pre- and postendarterectomy data, Dr. Connolly and colleagues found a marked correlation between cerebral blood flow imbalance and cognitive dysfunction, “which also led us to believe that there is probably a blood flow issue rather than a microembolization issue at work here.”
In addition, two recent Japanese studies involving 158 patients who underwent endarterectomy demonstrated a marked correlation between clinical hyperperfusion syndrome and cognitive dysfunction. Furthermore, hyperperfusion was associated with reduced benzodiazepine receptor binding potential, indicating neuronal loss.