SHOULD PATIENTS WITH MULTIPLE SCLEROSIS GET FLU SHOTS?

Due to the temporal association of the clinical exacerbation of multiple sclerosis and upper respiratory tract infection, the safety of influenza vaccination has been a concern. Although previously published studies have not demonstrated that influenza vaccination exacerbates multiple sclerosis, the authors of this study monitored myelin-protein specific T-cell responsiveness at the single cell level by enzyme-linked immunospot analysis and by PCR analysis of autoantigen-induced expression of interferon-g messenger ribonucleic acid.

Influenza vaccination is effective and safe in patients with multiple sclerosis, according to the results of a study by researchers from Julius-Maximilians University, Würzburg, Germany. “Because vaccination can protect against or attenuate influenza disease, notably not other viral diseases with similar immunoactivating effects, it should be recommended for patients with MS who are at risk of infection-associated exacerbations or deterioration,” advised the authors.

The study cohort included 12 patients with multiple sclerosis and 28 healthy individuals before and for four months after they received an influenza vaccination. Both groups demonstrated a cellular immune response against the influenza A virus at two weeks, and patients with multiple sclerosis showed a higher relative increase than did controls of the number of influenza-specific T cells. However, the study did not indicate any increase in T-cell frequency response to human myelin basic protein or recombinant human myelin oligodendrocyte protein In fact, T-cell response to myelin basic protein was only detectable after febrile infection, noted the authors in the April 10 Neurology. Furthermore, vaccination was not associated with either deterioration of neurologic symptoms or with other serious side effects in patients with multiple sclerosis.

The authors noted that relevant autoantigens in multiple sclerosis remain unidentified. Proteolipid protein, myelin-associated glycoprotein, CNPase, aBCrystallin, and S100ß may play a role in the development of the disease. However, the response of these autoantigens to influenza vaccination was not assessed in this study. The authors added that previously published trials have linked MOG-specific T-cell response to clinical activity in patients with multiple sclerosis.

Suggested Reading
Moriabadi NF, Niewiesk S, Kruse N, et al. Influenza vaccination in MS: absence of T-cell response against white matter proteins. Neurology. 2001;56:938-943.

EPILEPSY DRUGS PINPOINTED AS CAUSE FOR FETAL MALFORMATIONS

Anticonvulsant medication taken during pregnancy, rather than the mother’s epilepsy itself, appears to be the cause of fetal malformations. According to a study in the April 12 New England Journal of Medicine, there is a distinctive pattern of physical abnormalities in infants whose mothers used anticonvulsant drugs during pregnancy.

Researchers screened 128,049 women in labor and delivery suites to identify three groups of infants: those whose mothers took anticonvulsant drugs during pregnancy, those whose mothers had epilepsy but took no anticonvulsant during pregnancy, and those whose mothers had no history of epilepsy. The infants were examined for the presence of major malformations, hypoplasia of the midface and fingers, microcephaly, and small body size, in addition to 53 minor physical features.

The 223 infants exposed to a single anticonvulsant drug taken by the mother during pregnancy had a significantly higher frequency of physical abnormalities (20.6%) than the group of 508 control infants (8.5%). The frequency of major malformations increased for the group of 93 infants exposed to two or more anticonvulsant drugs (28%). The group of 98 unexposed infants born to women with a history of seizure, however, did not have an increased rate of abnormalities.

Compared to the control group, malformations were more likely to occur in the 87 infants exposed to phenytoin alone and the 64 infants exposed to phenobarbital alone. The frequency of major malformations, microcephaly, and growth retardation, but not hypoplasia of the midface and fingers, was higher in the 58 infants exposed to carbamazepine. The researchers pointed out that marked hypoplasia of the nails plus stiff joints are known to be more common with phenytoin exposure; lumbosacral spina bifida is more common with carbamazepine or valproic acid exposure.

Embryopathy was correlated with exposure to anticonvulsant drugs, regardless of the underlying maternal illness being treated. “Infants of women who had taken anticonvulsant drugs as treatment for mood disorders, migraine, or pain had an increase in the frequency of embryopathy that was similar to that among infants of women with epilepsy,” they said.

“We found no evidence that infants born to women with a history of epilepsy who took no anticonvulsant drugs during pregnancy had an increased risk of the pattern of physical abnormalities associated with exposure to anticonvulsant drugs,” the researchers concluded.

Suggested Reading
Holmes LB, Harvey EA, Coull BA, et al. The teratogenicity of anticonvulsant drugs. N Engl J Med. 2001;344:1132-1138.

WHAT ROLE SHOULD THE GOVERNMENT PLAY IN REGULATING THE DIETARY SUPPLEMENT INDUSTRY?

Americans appear to be ambivalent about what role the government should play in regulating the dietary supplement industry, according to a study in the March 26 Archives of Internal Medicine. The majority of Americans surveyed agreed that the Food and Drug Administration (FDA) should review new dietary supplements prior to their sale, recall unsafe supplements, and ensure that marketing claims about supplements are true. However, only 25% of survey respondents said they would stop using a dietary supplement that was found clinically ineffective by a government agency; and only 33% of respondents said they would stop using products found clinically ineffective by the FDA.

According to the survey, 48% of Americans reported using a nonprescription vitamin, dietary, or mineral supplement regularly. Dietary supplement sales for 2000 are estimated at $15.7 billion. Sales of remedies that incorporate echinacea, ginseng, Ginkgo biloba, or St. John’s wort exceed $200 million per herb, annually. This huge industry is very loosely regulated, and currently, dietary supplement manufacturers may make general rather than specific health claims. Moreover, the manufacturer does not need to demonstrate product safety; the FDA must demonstrate harm. The authors noted that although questions about the safety and efficacy of dietary supplements have been raised in medical journals and in other media, the role of the government in regulating dietary supplements has remained under debate.

Regular users of dietary supplements are most likely to be non-Hispanic white, older than age 45, more highly educated than non-users, and insured. A similar number of men and women use supplements regularly. The survey indicated that 52% of Americans believe that supplements are good for health and well-being; 49%, for influenza; 61%, for colds; 35%, for cancer; 16%, for acquired immunodeficiency syndrome; 53%, for arthritis; and 52%, for depression.

Although approximately half of Americans occasionally or regularly take supplements, half of all respondents indicated distrust in supplement manufacturers: the survey showed that 48% believe that products are inadequately tested; 49% believe that advertisements are untrue; and 47% believe that people are sometimes or often hurt by supplements.

Just as Americans are skeptical about the safety of supplements, they are skeptical about safety trials and about discussing safety issues with their physicians. While 80% of respondents agreed that the FDA should withdraw supplements that are proven unsafe, 71% of regular users would continue to use a product found clinically ineffective. Although 70% of regular users had told their physician about their supplement use, 49% believe physicians are prejudiced about supplements, and 44% believe their own physician lacks knowledge about these products.

The authors noted that it is important that physicians become more knowledgeable about dietary products and discuss safety issues with their patients. “The fact that one of six parents reported giving these supplements to their children should prompt physicians to devote more attention to discussing this practice with parents as they seek health care for their children,” the authors added.

Suggested Reading
Blendon RJ, DesRoches CM, Benson JM, et al. Americans’ views on the use and regulations of dietary supplements. Arch Intern Med. 2001;161:805-810.

BENEFITS FROM ENDARTERECTOMY INCREASE WITH AGE

In the prevention of ischemic stroke, elderly patients benefit more from carotid endarterectomy than younger patients, according to a post hoc subgroup analysis of the North American Symptomatic Carotid Endarterectomy Trial. Severity of illness and comorbidity are more important predictors of surgical complications than age alone, the research suggested.

The risk of ipsilateral ischemic stroke at two years after carotid endarterectomy was assessed in patients older than 75 years, patients between the ages of 65 and 74, and patients younger than 65. Compared to the younger patients, the elderly group had less severe carotid atherosclerotic disease, a lower frequency of intermittent claudication, and a lower prevalence of contralateral occlusion, the researchers noted.

Among patients with 70% to 99% stenosis, the absolute risk reduction of stroke after surgery was better for the elderly group (28.9%) compared to those in the medium age group (15.1%) and youngest age group (9.7%), the researchers reported in the April 14 Lancet. Among patients with 50% to 69% stenosis, risk reduction was significant only in the patients ages 75 and older. The perioperative risk of stroke and death at any degree of stenosis was 5.2% for the elderly group, 5.5% for the medium age group, and 7.9% for the youngest age group.

Among patients ages 75 or older, only three with severe stenosis and only six with moderate stenosis would have to undergo endarterectomy to prevent one ischemic ipsilateral stroke in two years, the researchers said. “These good results can only be achieved in elderly patients after a scrupulous clinical evaluation to exclude disorders that could put the patients at increased risk from anaesthesia or of immediate cardiac complications, and with endarterectomy done by skilled surgeons,” they concluded.

Although none of the endarterectomy trials to date have included patients older than 90, a review of the literature suggests that those older than 75 stand to gain the most from surgery, said Peter M. Rothwell, MD, in an accompanying commentary. “Even if the operative risk of stroke and death for very old people is as much as 10%, which is higher than is generally reported, endarterectomy would still be beneficial because of the high risk of stroke without surgery,” he said. Furthermore, the reduction in stroke risk after endarterectomy for severe symptomatic carotid stenosis is evident within six months of surgery and peaks by two years, suggesting that most 85-year-old patients would survive long enough to benefit. Elderly patients commonly do not wish to undergo endarterectomy, Dr. Rothwell said, but he argued they should at least be given the choice.

Suggested Reading
1. Rothwell PM. Carotid endarterectomy and prevention of stroke in the very elderly. Lancet. 2001;357:1142-1143.
2. Alamowitch S, Eliasziw M, Algra A, et al. Risk, causes, and prevention of ischaemic stroke in elderly patients with symptomatic internal-carotid-artery stenosis. Lancet. 2001;357:1154-1160.

ARE THERE BIOLOGICAL MARKERS FOR ALZHEIMER’S DISEASE?

Cerebrospinal fluid levels of tau and ß-amyloid proteins ending at amino acid 42 (Aß42) may be biomarkers for Alzheimer’s disease. These markers may be particularly useful in differentiating cognitive impairment associated with Alzheimer’s disease from the effects of normal aging and other neurologic or psychiatric disorders, suggested Swedish researchers.

Of the 265 patients with cognitive impairment who were consecutively admitted to the hospital in Piteå, Sweden, 241 patients (91%) agreed to undergo lumbar puncture. Diagnostic evaluation of this cohort indicated that 105 had probable Alzheimer’s disease, 58 had possible Alzheimer’s disease, 23 had vascular dementia, 20 had mild cognitive impairment, nine had Lewy body dementia, three had other neurologic disorders, five had other psychiatric disorders, and 18 were not demented.

According to the study in the March Archives of Neurology, patients with probable or possible Alzheimer’s disease had increased levels of tau and decreased levels of Aß42 in their cerebrospinal fluid. The combined sensitivity of these assays was 94%, 88%, and 75% for probable Alzheimer’s disease, possible Alzheimer’s disease, and mild cognitive impairment, respectively. Sensitivity was further increased to nearly 100% in patients with Alzheimer’s disease who had apolipoprotein, APOE*E4.

The authors noted that the biomarkers were also sensitive for other neurologic diseases, such as Creutzfeldt-Jakob disease. Such sensitivity is a drawback to clinical applications of the assays for the diagnosis of Alzheimer’s disease. Thus, their most important application may be the differentiation of Alzheimer’s disease from normal aging and psychiatric disorders such as depressive pseudodementia, the authors suggested.

The association of increased tau and decreased Aß42 in the cerebrospinal fluid with possible and probable Alzheimer’s disease is “reassuring and encouraging for the future use of these assays,” said David Knopman, MD, in an accompanying editorial. However, he suggested that the evaluation of cerebrospinal fluid for the diagnosis of Alzheimer’s disease may be more useful for general physicians than for specialists.

“Neurologists, geriatricians, and psychiatrists who see many cases of dementia can usually make the diagnosis with confidence,” said Dr. Knopman. “However, among a large group of other physicians, the diagnosis of Alzheimer’s disease is perceived as uncertain.” Dr. Knopman is a neurologist at the Mayo Clinic, Rochester, Minnesota.

He noted that the study findings are important, even though they may not lead to widespread clinical use of the assays for diagnostic purposes. These assays may be used to identify people at risk for developing Alzheimer’s disease before they show clinical signs of the disease, he said. “In a predictive capacity, in contrast to a confirmatory capacity, there is no ceiling on the additive value of CSF Aß and tau protein testing,” he concluded.

NR