Author + information
- Received April 3, 2012
- Revision received June 12, 2012
- Accepted June 26, 2012
- Published online October 23, 2012.
- Daryl R. Gress, MD⁎ ()
Reprint requests and correspondence:
Dr. Daryl R. Gress, Department of Neurology, University of Virginia, Box 800394, Charlottesville, Virginia 22908
Cerebral embolic events related to carotid and cardiac disease have been known for decades. Recently, cerebral embolic events have become a focus of clinical importance as complications of vascular procedures. Further, the development of new technologies and procedures has increased the overall clinical significance. Although the relative safety of these procedures is usually defined by acute stroke risk, it is also becoming clear that far more subclinical events are occurring. Recent reports provided substantial evidence of memory loss, cognitive decline, and dementia related to these so-called silent infarcts. Literature reports of magnetic resonance imaging events lead to an estimate of as many as 600,000 patients with new brain injury each year in the United States alone. Given the magnitude of the numbers involved, the impact of accelerated cognitive loss and premature senescence in a vulnerable at-risk population could well be significant.
Cerebral embolic events related to carotid and cardiac disease have been known for decades and have formed a central part of clinical stroke research and management. More recently, cerebral embolic events have become a focus of clinical importance as complications of vascular procedures. Surgical and endovascular procedures, both neurointerventional and cardiac, are associated with embolic risks, and the development of new technologies and procedures has increased the overall clinical significance. Although the relative safety of these procedures is usually defined by the acute stroke risk, it is also becoming clear that far more subclinical events are occurring. Although the fundamental issues of the nature of the embolic particles, precise mechanisms of cerebral injury, and effective prevention remain debated and unclear, recent reports have provided substantial evidence of memory loss, cognitive decline, and dementia related to these so-called silent infarcts.
The Question: Are These Events Really Asymptomatic?
In the world of stroke neurology, the early concept of multi-infarct dementia has rapidly evolved to one of vascular cognitive decline. It is clear that cerebral vascular disease and cognitive decline travel hand in hand. Vascular risk factors of hypertension, hyperlipidemia, and ischemic white matter disease favor the premature appearance of dementia. It may well be that the age at which noticeable cognitive loss develops depends on the aggregate accumulation of aging neurons and focal tissue injury. In a recent study, 717 individuals >65 years of age without dementia were enrolled in a study involving magnetic resonance imaging (MRI) and extensive neuropsychological testing (1). Not surprisingly, mild cognitive impairment was found commonly and associated with decreased hippocampal volume, presumably secondary to neuronal aging and atrophy. But the most notable finding was the association of cortical or subcortical infarctions with memory impairment. The study counted infarcts of ≥3 mm, most clinically silent, and demonstrated an independent association with global memory dysfunction. Recent reports based on neuropathological findings demonstrated that even microinfarctions are associated with lower cognition and memory, especially if multiple lesions are present (2,3).
The Problem: The Potential Problem Is Large
The annual number of patients in the United States who undergo surgical or endovascular procedures related to cerebral, carotid, or coronary disease is sizable, and the resulting number of patients at risk of cerebral infarcts is significant and troubling. Looking at the most common vascular procedures leads to an estimate of >2.5 million patients treated annually, many with multiple procedures. This number would be predicted to continue to grow, with expanding indications for newer procedures such as transaortic valve implantation and atrial fibrillation ablation. Reviewing literature reports of MRI events associated with various procedures leads to an estimate of as many as 600,000 patients with new brain injury each year in the United States alone (Table 1). This number is likely an underestimate of the true phenomenon. More sensitive imaging with high field strength, 3-T magnetic resonance scanners demonstrated ∼30% more diffusion-weighted imaging (DWI) lesions than the conventional 1.5-T units in a study of patients after carotid stenting and endarterectomy (4). The occurrence of procedure-related asymptomatic lesions likely rivals clinical stroke, estimated at ∼750,000 cases per year in the United States.
Routine MRI of patients before and after vascular procedures has provided insight into this issue and fueled concern for the problem. Ischemia rapidly leads to cellular events that restrict free movement of water molecules. These bright DWI lesions represent foci of restricted diffusion of water and are both quite sensitive and quite specific for acute ischemia. Although reversible ischemia, and therefore reversible diffusion restriction, without infarction is possible, it is rarely seen in clinical settings. In clinical applications, DWI lesions are most likely infarctions with permanent tissue loss. These silent DWI lesions typically are small (1 to 3 mm) but can be larger. Multiple lesions per procedure are commonly noted, with 1 to 5 commonly described.
Carotid stenting provides an illustrative example. Early reports describing MRI before and after carotid stenting demonstrated small lesions with DWI sequences. These DWI lesions were seen in patients both with and without clinical stroke symptoms. Although the clinical stroke rate may have been only a few percent, DWI lesions are seen in many more. A meta-analysis performed in 2008 reviewed studies totaling 1,363 stenting cases and a rate of new DWI lesions of 37%. The use of a distal protection device appeared to reduce the risk from 45% to 33% (5). A substudy of the International Carotid Stenting Study looked at 124 stent patients and found a rate of new DWI lesions of 50% at 1 day with 33% of those lesions remaining apparent on MRI at 1 month (4). Several studies of small numbers of patients failed to link DWI lesions and neurological deficits.
Cardiac procedures, including atrial fibrillation ablation, transaortic valve implantation, coronary artery bypass graft, and even coronary angiography procedures, have significant rates of new DWI lesions (Table 1). These rates are much higher than the procedural symptomatic stroke risk, and a degree of clinical concern seems warranted.
It has been known for many years that declines in neurological and cognitive function have followed coronary bypass graft surgery. It has been difficult to further define the basis of the “just not quite right” syndrome. Efforts to avoid bypass itself have not eliminated the subsequent cognitive and memory loss. In a 2006 review by Bendszus and Stoll (6), DWI lesions were reported to occur in 16% to 45% of patients. The clinical significance of the DWI lesions and subsequent neurological status in the post-bypass patients remains unclear.
The Challenge: How to Find the Answers
The current practice of vascular procedures and interventions provides important clinical benefit, with reasonable and demonstrated safety, across a vast section of predominantly older individuals. However, available data would suggest that new silent infarctions are much more frequent than one would have supposed. Although there is no current clinical proof of neurological sequelae, the data are accumulating to suggest that there may be a problem. Given the magnitude of the numbers of individuals involved, the impact of accelerated cognitive loss and premature senescence in a vulnerable at-risk population could well be significant. The eventual management of these risks will require multiple strategies, including improved pharmacological manipulation of clotting and platelet aggregation, safer device design and technique, and development of effective protection devices.
At this point, I would argue for 2 conclusions. 1) We must work to develop safer procedures with decreased risk of microinfarctions using DWI lesions as a marker. 2) We are obligated to take on the effort to study the long-term sequelae of these DWI lesions, recognizing that this is a monumental undertaking requiring extensive planning and expense.
The author notes the valuable assistance of Karen Davis in the preparation of this manuscript.
Dr. Gress is a member of the Scientific Advisory Boards of Keystone Heart and Ornim Medical and holds stock options in the companies, and is also a consultant to Medtronic.
- Abbreviations and Acronyms
- diffusion-weighted imaging
- magnetic resonance imaging
- Received April 3, 2012.
- Revision received June 12, 2012.
- Accepted June 26, 2012.
- American College of Cardiology Foundation
- Arvanitakis Z.,
- Leurgans S.E.,
- Barnes L.L.,
- Bennett D.A.,
- Schneider J.A.
- Schnaudigel S.,
- Groschel K.,
- Pilgram S.M.,
- Kastrup A.