TWO PERSPECTIVES OF MS DISABILITY

Multiple sclerosis (MS) patients’ perception of change in disability differs not only quantitatively but also qualitatively from that of a physician, according to a longitudinal study published in the April Journal of Neurology, Neurosurgery and Psychiatry. Investigators aimed to characterize the relationship between one-year changes in neurologist ratings of exam abnormalities, measured by the Expanded Disability Status Scale (EDSS), and changes in the patient’s perceived disability, measured by the Guy’s Neurological Disability Scale (GNDS).

Researchers recruited 250 patients with MS from an outpatient clinic. The patients’ disability was determined at baseline and after one year using the EDSS and the GNDS. The investigators determined the cross-sectional correlation between EDSS and GNDS sum score at baseline and follow-up, and studied the longitudinal correlations between the change in EDSS and GNDS sum scores, the change in functional systems, and the change in GNDS subcategories. They also noted the number of patients showing a clinically significant change on the EDSS and GNDS, in addition to the mean change in GNDS for patients with a change on the EDSS.

Investigators found that the correlation between one-year changes in EDSS versus GNDS was significantly lower than cross-sectional correlations between the two scales at baseline and at follow-up. Interestingly, they found opposite changes in EDSS scores and GNDS scores in 8% of patients. In addition, the researchers also reported that “dependent on the criterion applied for significant change in the GNDS, 10% to 22% of the patients who have a significant worsening on the EDSS show a significant improvement in perceived disability.” Three reasons given for the discrepancies in the change in scores were “differences in the change perceived by the patient and that measured by the physician, changes in many disability subcategories not leading to changes in EDSS, and the GNDS incorporating aspects of disability (for example, fatigue) that are not at all considered by the EDSS.”

Suggested Reading
Hoogervorst ELJ, Eikelenboom MJ, Uitdehaag BMJ, Polman CH. One year changes in disability in multiple sclerosis: neurological examination compared with patient self-report. J Neurol Neurosurg Psychiatry. 2003;74:439-442.

INVASIVE ASSESSMENT OF HEART VALVE STENOSIS INCREASES RISK OF EMBOLISM

Undergoing retrograde catheterization of the aortic valve to assess the severity of valvular aortic stenosis increases the risk of cerebral embolism, according to a study in the April 12 Lancet. While the severity of valvular aortic stenosis can be accurately assessed noninvasively by echocardiography, retrograde catheterization of the aortic valve is often undertaken, especially for patients awaiting valve replacement. Researchers sought to determine the frequency of “clinically apparent and silent cerebral embolism after this procedure.”

The investigators randomized 152 patients with valvular aortic stenosis; 101 received cardiac catheterization with passage through the aortic valve, and 51 received aortic catheterization without passage through the valve. Thirty-two individuals without valvular aortic stenosis who underwent coronary angiography served as the control group for the study. All participants underwent cranial MRI one day prior to and within two days after the procedure to assess cerebral embolism, and had a neurologic assessment before and one day after catheterization.

After the procedure, 22% of patients who underwent retrograde catheterization of the aortic valve had indications of cerebral blood clots from MRI scans; three of these had impaired neurologic function. Researchers observed a total of 30 acute cerebral diffusion abnormalities, and four patients had more than one embolic lesion. By contrast, none of the patients who did not undergo catheterization through the aortic valve, or any of the controls, had evidence of cerebral blood clots. The investigators believe that patients should be informed “about these procedure-related risks, and retrograde catheterization of the stenotic aortic valve should only be undertaken when patients’ echocardiographic findings are unclear and additional information is essential for clinical management.”

Suggested Reading
Omran H, Schmidt H, Hackenbroch M, et al. Silent and apparent cerebral embolism after retrograde catheterisation of the aortic valve in valvular stenosis: a prospective, randomised study. Lancet. 2003;361:1241-1246.

EPSTEIN-BARR ANTIBODIES ELEVATED PRIOR TO MS ONSET

There is a relationship between Epstein-Barr virus and the development of multiple sclerosis (MS), suggests a study in the March 26 JAMA. While previous research has associated the virus with an increased risk of MS, the temporal relationship between the two has remained unclear. The investigators sought to determine whether antibodies to Epstein-Barr virus are elevated prior to the onset of MS.

Researchers assessed the blood samples of more than three million military personnel whose blood was collected upon entry into the military and every two years thereafter since 1988. Cases were identified by searching databases for any personnel granted disability due to MS. For each of the 83 cases, the investigators identified the earliest available serum sample, plus two samples collected before MS onset and the first sample collected after onset. Each case was matched to two controls with the same sex and ethnicity, and similar ages and dates of blood collection. The blood samples were analyzed for various Epstein-Barr virus antibodies.

All of the cases and 96% of the controls showed evidence of Epstein-Barr virus infection at baseline, and the mean time between initial blood collection and the MS onset was four years. The researchers found that “the baseline mean serum antibody titers to Epstein-Barr virus were consistently higher among individuals who later developed MS than among their matched controls.” They noted that the lack of variation in antibody concentrations between blood samples collected six to 11 years prior to onset and those taken later suggests that “the increased antibody response to Epstein-Barr virus occurs early in relation to the pathological process that leads to demyelination and clinical disease.”

Suggested Reading
Levin LI, Munger KL, Rubertone MV, et al. Multiple sclerosis and Epstein-Barr virus. JAMA. 2003;289:1533-1536.

ATORVASTATIN REDUCES RISK OF MAJOR CORONARY EVENTS

Treatment with atorvastatin for the prevention of coronary heart disease has resulted in significant reductions in major cardiovascular events, according to the results of a large multicenter trial published in the April 5 Lancet. The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) was designed to compare two antihypertensive treatment strategies for the prevention of coronary heart disease events in hypertensive patients who have no history of coronary heart disease. The researchers assessed the benefits of lowering cholesterol in the primary prevention of heart disease in hypertensive patients who have not been diagnosed dyslipidemic.

Researchers recruited 10,305 patients (81% male) between the ages of 40 and 79 for inclusion in the lipid-lowering arm of ASCOT. To qualify for this portion of the trial, “patients had to be eligible for the blood-pressure-lowering arm, have total cholesterol concentrations of 6.5 mmol/L or lower, and not currently be taking a statin or a fibrate.” In addition, the patients had to have at least three risk factors for cardiovascular disease. The participants were randomly assigned to take 10 mg/day of atorvastatin or placebo, and were asked about any new cardiovascular events or procedures at each follow-up.

The lipid-lowering arm of the trial was terminated after a median follow-up of 3.3 years “on the grounds that atorvastatin had resulted in a highly significant reduction in the primary end point of coronary heart disease events compared with placebo and a significant reduction in the incidence of stroke.” Patients taking atorvastatin saw a 36% reduction in myocardial infarctions compared with the placebo group. Additionally, after a one-year follow-up, total cholesterol and LDL-cholesterol among those taking the drug were 24% and 35% lower, respectively, than among those taking placebo.

However, in an accompanying editorial, Lars H. Lindholm, MD, PhD, and Ola Samuelsson, PhD, posited that the results of the ASCOT trial should be compared with those of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), published in the December 18, 2002, JAMA. They noted that the trial design was similar to that of ASCOT, but 50% of the patients were women. Though the patients were randomly assigned to 40 mg/day of pravastatin or to usual care for more than four years, the trial “failed to show a benefit in all-cause mortality (primary outcome) or in non-fatal myocardial infarction and fatal coronary heart disease (secondary outcomes).”

Suggested Reading
Lindholm LH, Samuelsson O. What are the odds at ASCOT today? Lancet. 2003;361:1144-1145.
Sever PS, Dahlöf B, Poulter NR, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial–Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet. 2003;361:1149-1158.

E-DIARIES MAY HELP MIGRAINEURS PREDICT ATTACKS

Approximately 72% of migraineurs who reported premonitory symptoms experienced a migraine within 72 hours nearly 50% of the time, according to research in the March 25 Neurology. Researchers speculated that the ability to accurately predict a migraine could improve the chances of preventing or minimizing it. They believed that determining a link between the premonitory and headache phases of migraine would give “clinical weight to electrophysiologic evidence of functional changes that start before the headache,” and it would allow researchers “to investigate the therapeutic potential for the management of migraine in the premonitory phase.”

Ninety-seven patients (mean age, 42; 95% women) with migraines were recruited for the three-month study. Each participant was assigned a handheld electronic diary programmed with questions to prospectively record nonheadache symptoms before, during, and after attacks. Data collected during diary entries included the onset of nonheadache features, the prediction of an imminent migraine, and onset and severity of migraine. Each entry could not be altered once it was entered into the diary.

The investigators found that when premonitory symptoms were reported, they were followed by a migraine within 72 hours on 72% of occasions. The most common symptoms were tiredness, reported in 72% of episodes with premonitory symptoms, followed by difficulty concentrating (51%) and stiff neck (50%); however, the researchers reported that excessive yawning was among the best predictors of a migraine attack. They determined that changes in the central nervous system begin up to three days prior to a migraine and carry on into the postdrome, “giving clinical weight to evidence of electrophysiologic changes starting more than 24 hours before the headache.” Additionally, because excessive yawning is associated with dopamine release, the investigators posit that “dopaminergic mechanisms, possibly involving the brain stem nuclei, may play a role in the premonitory phase.”

NR

Suggested Reading
Griffin NJ, Ruggiero L, Lipton RB, et al. Premonitory symptoms in migraine: an electronic diary study. Neurology. 2003;60:935-940.

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