MRI MAY HELP IN EARLY DIAGNOSIS OF MS

In patients who first present with isolated syndromes suggestive of multiple sclerosis, the increases in the volume of lesions seen on magnetic resonance imaging (MRI) of the brain in the first five years correlate with the degree of long-term disability from the disease. However, because this correlation is only moderate, the number of lesions alone may not be an adequate basis for making decisions about the use of disease-modifying treatment, reported lead investigator David H. Miller, MD, of the Institute of Neurology in London, and colleagues in the January 17 New England Journal of Medicine.

A total of 109 patients were recruited for clinical and MRI examinations at baseline and after approximately one year. Seventy-one individuals with isolated syndromes were reassessed after a mean of 14.1 years. Disability was measured by using Kurtzke’s Expanded Disability Status Scale (EDSS) (range of 0 to 10, with a higher score indicating a greater degree of disability).

The cohort of 71 did not differ significantly from the original group in age at presentation, sex, type of syndrome, or frequency and volume of abnormalities on MRI at presentation. Three individuals died from complications of severe multiple sclerosis by year 14, 55 visited the hospital and underwent a neurologic and MRI examination, and 13 underwent EDSS assessment over the telephone.

Clinically definite multiple sclerosis developed in 44 of 50 patients (88%) with abnormal results on MRI at presentation and in four of 21 patients (19%) with normal results on MRI. The median EDSS score at follow-up for those with multiple sclerosis was 3.25; 31% had an EDSS score of six or more. The EDSS score at 14 years correlated moderately with lesion volume on MRI at five years and with the increase in lesion volume over the first five years.

In an accompanying editorial, Donald W. Paty, MD, of the Vancouver Hospital, and Douglas L. Arnold, MD, of the Montreal Neurological Hospital, said, “It is clear from [this study] that the presence of lesions of multiple sclerosis on MRI at the onset of symptoms of multiple sclerosis and the changes on MRI over time have predictive value…. The number and extent of the lesions, especially in the early years, were significant predictors of prognosis.”

Suggested Reading
1. Brex PA, Ciccarelli O, O’Riordan, JI, et al. A longitudinal study of abnormalities on MRI and disability from multiple sclerosis. N Engl J Med. 2002;346:158-164.
2. Paty DW, Arnold DL. The lesions of multiple sclerosis: an editorial. N Engl J Med. 2002;346:199-200.

INFLUENZA VACCINE MAY HELP PREVENT STROKE

Influenza vaccination is negatively associated with ischemic stroke, particularly in patients younger than age 75, a finding that suggests that the flu vaccine may protect against brain infarction.

“Our results provide indirect evidence that infection or inflammation plays a key role in cardiovascular thrombotic events. They also open up new avenues for research into stroke prevention,” said Philippa Lavallée, MD, of the Denis Diderot University in Paris, and colleagues in the February Stroke. The investigators said that the vaccination may help protect against brain infarction by reducing infections or may identify a subgroup of patients at low risk for stroke because of a better lifestyle.

Dr. Lavallée and colleagues studied 270 subjects during an influenza epidemic period, including 90 consecutive patients older than age 60 admitted to the hospital for brain infarction and 180 population-based controls, matched for age, sex, and district of residency in Paris. They then conducted a structured interview on whether the individuals had been vaccinated during the last influenza vaccination campaign or every year for the last five years.

The researchers found significantly fewer vaccinated subjects during the last vaccination campaign among patients with brain infarction than among controls (46.7% versus 59.4%, respectively) and fewer patients vaccinated every year during the last five years (41.1% versus 56.1%). After adjusting for age, traditional risk factors, and recent use of antibiotics, the risk of stroke was reduced in the subjects vaccinated during the year of the study and in those vaccinated during the preceding five years. Similar associations were seen in cases and controls free of previous cardiovascular history. Subjects younger than 75 years and those free of risk factors or in a high social class were significantly less often vaccinated than were controls. The investigators found that the result was no longer significant after age 75 and was strongly significant in patients younger than age 75.

The researchers said that one explanation for their findings could be that with increasing age, the influence of traditional risk factors such as hypertension is too great to detect a significant direct effect of influenza vaccination. “In fact, we found a very significant interaction between age and hypertension and between age and history of stroke, which are both the highest risk factors for incident stroke,” said Dr. Lavallée and colleagues.

Suggested Reading
1. Lavallée P, Perchaud V, Gautier-Bertrand M, et al. Association between influenza vaccination and reduced risk of brain infarction. Stroke. 2002;33:513-518.

INCREASED PLASMA HOMOCYSTEINE INCREASES RISK FOR DEMENTIA

An effort to define the link between elevated plasma homocysteine levels and dementia resulted in “the clearest demonstration yet” that the relationship between the two conditions is indeed causal, and that an increased plasma homocysteine level “is a strong, independent risk factor for the development of dementia and Alzheimer’s disease.”

Philip A. Wolf, MD, and colleagues examined 1,092 dementia-free subjects (667 women and 425 men, mean age 76) from the Framingham Study. Total plasma homocysteine levels were measured at baseline in all subjects and again at the end of follow-up (median 8 years). Dementia developed in 111 subjects (74 women, 37 men) and 83 of these subjects (62 women, 21 men) were diagnosed with Alzheimer’s disease.

Data analysis revealed that for each increase of 1 SD in log-transformed baseline homocysteine levels, the relative risks of dementia and Alzheimer’s disease were 1.3 and 1.4, respectively. “An increase in the plasma homocysteine level of 5 µmol/liter increased the risk of Alzheimer’s disease by 40%,” and a level “in the highest age-specific quartile doubled the risk of dementia or Alzheimer’s disease,” the researchers added. Adjustment for age, sex, APOE genotype, plasma vitamin levels, and other putative risk factors for dementia and Alzheimer’s disease did not significantly alter these increases.

The results of the trial were reported in the February 14 New England Journal of Medicine. Dr. Wolf and colleagues concluded that while there is a “strong, graded association between plasma total homocysteine levels and the risk of dementia and Alzheimer’s disease,” it will require “further elucidation of the pathophysiologic mechanisms and direct evidence from controlled clinical trials in humans” to determine whether interventions such as B vitamins, which reduce plasma homocysteine levels, can thereby reduce the risk of clinical dementia and Alzheimer’s disease.

Suggested Reading
1. Seshadri S, Beiser A, Selhub J, et al. Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med. 2002; 346:476-483.

WILL A DRINK A DAY KEEP DEMENTIA AWAY?

Light-to-moderate alcohol consumption is associated with a reduced risk of dementia in individuals ages 55 and older, according to a new study in the January 26 Lancet. Researchers at the Erasmus Medical Centre in Rotterdam, Netherlands, found that individuals in this age group who consumed between one and three glasses of alcohol per day had a 42% lower risk of developing dementia than did those who do not drink alcohol.

The Rotterdam Study was a prospective, population-based trial of 7,983 participants. Annemieke Ruitenberg, MD, and colleagues examined all subjects who did not have dementia at baseline and who had complete data on alcohol consumption. A total of 5,395 participants completed reliable food-frequency questionnaires, which comprised 170 food items and all relevant beverages, including tea, coffee, and alcohol. The investigators used proportional hazards regression analysis, adjusted for age, sex, systolic blood pressure, education, smoking, and body-mass index, to compare the risk of developing dementia between individuals who regularly consumed alcohol and individuals who did not consume alcohol.

After an average follow-up of six years, 197 individuals developed dementia (146 Alz-heimer’s disease; 29 vascular dementia; 22 other dementia, including eight with Parkinson’s disease). Those who were not daily drinkers but who had more than one drink per week had a 25% lower risk than did non-drinkers, and those who drank less than one glass per week were 18% less likely than non-drinkers to develop dementia. Light-to-moderate drinking was significantly associated with a lower risk of any dementia (hazard ratio 0.58) and vascular dementia (hazard ratio 0.30).

Overall, the median alcohol consumption was 0.29 drinks per day. In men, the median was 0.87, and in women, it was 0.11. Men mainly consumed beer and liquor, and women primarily consumed fortified wine. The researchers found that the relationship between alcohol and dementia did not vary by type of alcoholic beverage.

Dr. Ruitenberg and colleagues suggested several mechanisms that could be responsible for the inverse relationship between consumption of alcohol and dementia. One is that alcohol may act through reduction of cardiovascular risk factors, either through an inhibitory effect of ethanol on platelet aggregation, or through alteration of the serum lipid profile. A second possible explanation is that alcohol might have a direct effect on cognition through release of acetylcholine in the hippocampus. A third is a possible interaction between APOE and alcohol consumption.

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