CORONARY ARTERY BYPASS GRAFT SURGERY AND COGNITIVE DECLINE

Measurable cognitive dysfunction is a common complication of coronary artery bypass graft (CABG) surgery, with an incidence between 80% and 90% at hospital discharge. Substantial evidence has implicated procedural aspects of CABG surgery. Chief among these is the use of cardiopulmonary bypass procedures. Therefore, a study published in the March 20 JAMA undertook to determine whether CABG surgery without the use of cardiopulmonary bypass would reduce the associated cognitive decline.

Diederik Van Dijk, MD, and colleagues in the Octopus Study Group randomized 281 patients (mean age, 61) to CABG surgery with cardiopulmonary bypass (on-pump; n = 139) or without cardiopulmonary bypass (off-pump; n = 142). Psychologists determined cognitive outcomes at three and 12 months through the comparison of 10 neuropsychologic tests given before and after surgery. Results for 248 patients demonstrated that at three months, cognitive decline occurred in 21% of the off-pump group versus 29% of the on-pump group. At 12 months, decline was seen in 30.8% of the off-pump patients and in 33.6% of the on-pump patients. No statistical differences were found between the procedures in quality of life, stroke rate, or all-cause mortality.

The researchers concluded that off-pump CABG surgery improved cognitive outcome at three months, “but the effects were limited and became negligible at 12 months,” thus apparently contradicting the theory that avoiding cardiopulmonary bypass will substantially preserve cognitive function in CABG patients. However, in an accompanying editorial, Daniel B. Mark, MD, MPH, and Mark F. Newman, MD, of Duke University Medical Center, were not quite so pessimistic.

They praised the Van Dijk study as “a welcome addition to the knowledge base,” and expressed some skepticism about the definitive nature of the results, based on what they viewed as flaws in the study design. Patients in the trial “were at a substantially lower risk for complications and cognitive dysfunction than patients routinely undergoing off-pump cardiopulmonary bypass in the United States,” the authors noted. They “averaged five years younger, had less advanced coronary artery disease, and less extracoronary vascular disease.” If a more representative group had been studied, “the incidence of cognitive dysfunction would likely have been significantly higher than the 29% observed [in the on-pump group] at three months and the power of the study to detect a benefit of off-pump cardiopulmonary bypass would have been enhanced,” he added.

According to Drs. Mark and Newman, it is nonetheless likely, as Dr. Van Dijk and colleagues concluded, that “avoiding cardiopulmonary bypass may not be enough to have a brain-safe CABG surgery.” Notwithstanding, they purport that “combining off-pump cardiopulmonary bypass with the new generation of anastomotic devices that permit proximal aortic graft attachment rapidly and without the need for aortic clamping may provide an even more powerful test for the hypothesis that making CABG surgery less invasive will provide better patient outcomes.”

Suggested Reading
Van Dijk D, Jansen EWL, Hijman R, et al. Cognitive outcome after off-pump and on-pump coronary artery bypass graft surgery: a randomized trial. JAMA. 2002;287:1405-1412.
Mark DB, Newman MF. Protecting the brain in coronary artery bypass graft surgery. JAMA. 2002;287:1448-1450.

PUFF THE MAGIC DRAGON?

A true biologic protective effect of cigarette smoking against the development of Parkinson’s disease finds support in a recent study of male twins. And not only is there a correlation, it’s a dose-related relationship. Researchers examined smoking behaviors in twins discordant for Parkinson’s disease; twins were chosen as subjects to control the potentially confounding effects of genetic factors. Published in the February 26 issue of Neurology, the results maintain that when the actual cumulative amount of cigarettes smoked was measured (in pack-years), the twin with Parkinson’s disease smoked significantly less than did his unaffected twin brother.

More than half a dozen studies and several prospective investigations have shown an inverse association between cigarette smoking and Parkinson’s disease. These studies place the risk of Parkinson’s disease in smokers at about half that of nonsmokers. Despite these repeated findings, a biological basis has yet to be established or universally accepted.

The researchers compared detailed smoking histories in male twin pairs identified from the National Academy of Sciences–National Research Council World War II Veterans Twins Cohort. They found 113 twin pairs in which at least one twin had Parkinson’s disease; in 33 discordant monozygotic pairs and 39 discordant dizygotic pairs in which at least one brother smoked, the twins without Parkinsons’s disease smoked more than their brothers &overall, the twin without Parkinson’s disease had smoked an average of 9.7 more pack-years than his twin with the disease. This was more marked in the monozygotic pairs, despite a high correlation for smoking, and is unlikely to result from either genetic factors or environmental confounders because these twin pairs are genetically identical and behaviorally similar.

Care was taken to limit the weaknesses of the study, and this is the only study to exclude a confounding effect of nuclear-encoded genes. To control for bias, cumulative smoking dose until disease onset and also until 10 years and 20 years before disease onset was calculated, “arguing against any major effect of early disease on reducing smoking behavior.” The authors acknowledged that diagnostic misclassification may have occurred, but to an extent unlikely to have had a major statistical impact. Recall bias should not be a major factor in the study, as most likely a positive association with smoking would not have been drawn by the subjects and in concordant pairs both historians had the disease, they uphold.

By controlling for genetic variability between case and control subjects, the authors believe that the study “adds weight to an accumulating body of evidence consistent with a protective effect of smoking on the development of Parkinson’s disease.”

Suggested Reading
Tanner CM, Goldman SM, Aston DA, et al. Smoking and Parkinson’s disease in twins. Neurology. 2002;58:581-588.

OLD MICROBLEEDS PREDICT CEREBAL BLEEDING AFTER ISCHEMIC STROKE

Seeking to improve the risk-to-benefit ratio of thrombolytic treatments, researchers at the Hôpital Neurologique in Lyon, France, studied whether the presence of old microbleeds in the brain was predictive of cerebral bleeding after ischemic stroke.

The study, published in the March Stroke, involved 100 patients (mean age, 60) who had documented ischemic damage. They were subjected to a battery of imaging tests, including a T2-weighted gradient-echo MRI, all performed within 24 hours after symptom onset. Results indicated that the presence of microbleeds was significantly related to the risk of cerebral bleeding. Patients with microbleeds were seven times more likely to develop cerebral bleeding after stroke compared with those without microbleeds. The study also indicated that the T2-weighted gradient-echo MRI was superior to other types of imaging at detecting microbleeds and cerebral bleeding, offering a higher sensitivity than conventional MRIs.

According to the researchers, the presence of microbleeds suggests an increased vascular vulnerability that may be exacerbated by hypertension, diabetes, and the chronic use of drugs to prevent blood clots. A trial with a larger cohort is needed to clearly establish the relationship and to determine whether the benefits outweigh the risks of using antithrombotic therapies in a subgroup at risk for both thrombotic and hemorrhagic events. However, the researchers urged practitioners “to carefully manage patients with diabetes and hypertension because of the increased risk of microbleeds and cerebral bleeding.” For this purpose, “the use of MRI as baseline imaging modality is warranted,” he added.

Suggested Reading
Nighoghossian N, Hermier M, Adeleine P, et al. Old microbleeds are a potential risk factor for cerebral bleeding after ischemic stroke. Stroke. 2002;33:735-742.

THE PEN IS MIGHTIER ...

Drawings “have been used for decades by child psychiatrists and psychologists to analyze children’s subjective feelings,” noted Carl E. Stafstrom, MD, PhD. Now they may be used to help identify whether children are experiencing migraine.

Because “children, especially younger ones, may have difficulty explaining their symptoms,” Dr. Stafstrom and colleagues surmised that pediatricians might be able to mitigate the diagnostic challenges presented by children with headaches by employing drawings. “Children are often expressive artists, and they can sometimes communicate more effectively through pictures than verbally,” he said. The results of the study were published in the March Pediatrics.

Prior to the taking of any history, 226 children (ages 4 to 19; mean 11.4) who were consecutively evaluated for headache were asked to draw a picture representing how their headache felt. To minimize bias, no leading questions or additional instructions were given. These pictures were then scored as “migraine” or “nonmigraine” by pediatric neurologists blinded to the children’s clinical history. Scores were compared to clinical diagnoses. Drawings with features consistent with migraine (eg, pounding pain, nausea/vomiting, desire to lie down, periorbital pain, photophobia, visual scotoma) had a predictive value of 87.1% for migraine.

Dr. Stafstrom encouraged the use of drawings as an adjunct to the clinical history and physical examination of any child with headache. “There are no tests for headacheæit’s an historical and subjective diagnosis, and every little bit [of data] helps,” he observed. Drawings provide “an inexpensive and easy way to get some additional information in a clinical setting.”

NR