VITAMIN C MAY REDUCE RISK OF STROKE

Epidemiologic evidence suggests that individuals with a high serum vitamin C concentration have significantly reduced risk of stroke, according to a long-term study reported in the October Stroke."To my knowledge, this is the first prospective study to make the correlation between vitamin C in the bloodstream and incidence of stroke," said lead author Tetsuji Yokoyama, MD, a research associate in epidemiology at the Medical Research Institute of Toyko Medical and Dental University. "The risk of stroke was inversely related to vitamin C in the bloodstream and frequency of vegetable consumption." Higher intake of fruits, vegetables, and other foods rich in vitamin C and potassium have been associated with lower stroke rates in previous studies.

In rural Japan, researchers examined a cohort of 880 men and 1,241 women ages 40 and older who were initially free of stroke when examined in 1977. Baseline examination included a measurement of serum vitamin C concentration. Incidence of stroke was determined by annual follow-up examinations. During the 20-year observation period, 196 strokes occurred, including 109 cerebral infarctions, 54 hemorrhagic strokes, and 33 strokes of undetermined type. The risk of stroke was 70% higher among those in the lowest quartile for serum vitamin C than among those in the highest.

Researchers examined the association of stroke and fruit and vegetable consumption by calculating the number of days per week the participants ate fruits and vegetables. The clearest association was for vegetable consumption. "The risk of all types of stroke was 58% lower among those who consumed vegetables six to seven days per week, compared to those who only consumed them up to two days a week," noted Dr. Yokoyama.

Higher concentrations of vitamin C in the blood provided benefits even in patients with other risk factors, such as high blood pressure, serum total cholesterol, body mass index, antihypertensive medication, atrial fibrillation, history of ischemic heart disease, heavier alcohol consumption, smoking, or lower physical activity. However, these risk factors did reduce the benefits somewhat. It is suspected that smoking and alcohol may inhibit vitamin C absorption or metabolism. "Thus, we recommend healthy behaviors such as eating fruits and vegetables frequently, not smoking, avoiding excess drinking, and being moderately physically active," Dr. Yokoyama said.

All study participants received vitamin C from natural foods; although blood vitamin C levels also rise with vitamin C supplementation, the researchers cannot confirm the same benefit from them. Because a risk reduction was observed in both types of stroke, Dr. Yokoyama said the responsible mechanism probably extends beyond vitamin C's known antioxidant effects. "One plausible explanation is that vitamin C may be a marker for higher intake of other nutrients that may protect against stroke," Dr. Yokoyama suggested. A high intake of fruits and vegetables is also associated with other healthy behaviors, and it is also hypothesized that vitamin C may lower blood pressure; vitamin C may reduce the risk of stroke through a combination of several mechanisms, the researchers allowed.

Mass screening of high-risk individuals to determine blood vitamin C levels would be instrumental in decreasing the rate of stroke—if appropriate control measures were developed, the authors noted. The researchers are preparing a database to analyze the association between blood levels of vitamin C and subsequent incidence of heart attack in the same population.

Suggested Reading
1. Yokoyama T, Chigusa D, Kokubo Y, et al. Serum vitamin C concentration was inversely associated with subsequent 20-year incidence of stroke in a Japanese rural community. Stroke.2000;31:2287-2294.

INITIAL DIAGNOSIS OF EPILEPSY SYNDROME IS USUALLY CORRECT

In most cases, the initial diagnosis of an epilepsy syndrome in a child is correct, according to the authors of a study in the October Epilepsia.At two years, only 13.7% of diagnoses changed. Change was due to either evolution of the syndrome or to rectification of the initial diagnosis.

The study, led by Anne T. Berg, PhD, was a follow-up to the authors' previous report in the April 1999 Epilepsia.In the most recent study, the initial diagnosis of epilepsy in 613 children was reviewed at two years. Etiology or syndrome could be reclassified because of a change in the syndrome or because of new evidence about an underlying etiology. Dr. Berg is Associate Professor of Epidemiology in the Department of Biological Sciences at the Northern Illinois University in DeKalb.

Of the 28 etiologic changes, 14 changes were due to a reclassification of the syndrome from cryptogenic to idiopathic, and one from idiopathic to cryptogenic. Evidence of a remote symptomatic etiology became apparent after the initial diagnosis in 12 cases. The authors explained that epilepsy syndrome was changed in 84 cases. The initially assigned syndrome was rectified in 60 cases and it truly evolved in 24. There are four highlights of the study, according to the authors. They noted that the 13.7% of children in the study whose syndrome was reclassified is comparable to the percentage reclassified in other studies. True evolution of syndrome, rather than error at initial diagnosis, was the basis for 29% of changes. More than half of the other changes were made to syndromes that had been partially classified at initial diagnosis due to inadequate data. Errors in the initial classification helped to identify limitations in the classification system.

The authors further recommended that patients receive adequate diagnostic assessments, including routine use of electroencephalography (EEG) and, when indicated, neuroimaging. They noted that the International League Against Epilepsy classification system cannot be meaningfully applied to cases that have not been evaluated with EEG and neuroimaging.

A five-year follow-up study of the accuracy of initial diagnosis of epilepsy is planned. "Identification of the underlying syndrome after five years, however, is not especially helpful if the syndrome is supposed to be used for prognosis and treatment decisions early in the course of the disorder," noted the authors. They suggested, however, that follow-up data will be a useful addition to knowledge about the etiology of the disease.

Suggested Reading
1. Berg AT, Shinnar S, Levy SR, et al. How well can epilepsy syndromes be identified at diagnosis? A reassessment 2 years after initial diagnosis. Epilepsia. 2000;41:1269-1275.
2. Berg AT, Shinnar S, Levy SR, Testa FM. Newly diagnosed epilepsy in children: presentation at diagnosis. Epilepsia.1999;40:445-452.

OBSTRUCTIVE SLEEP APNEA IS COMMON AMONG PATIENTS WITH REFRACTORY EPILEPSY

Patients with refractory epilepsy should be screened for obstructive sleep apnea, suggested a report in the October 10 Neurology.In this study sample, "previously undiagnosed obstructive sleep apnea was common, especially among men, older subjects, and those with seizures during sleep," the researchers said.

A total of 39 candidates for epilepsy surgery who did not have a history of obstructive sleep apnea underwent polysomnography to assess the relationship of interictal epileptiform discharges and sleep state. Subjects were also asked to complete the Sleep Apnea Scale of the Sleep Disorders Questionnaire and the Epworth Sleepiness Scale. One third of the subjects (13) had respiratory disturbance indexes of five or greater, the researchers reported. Six subjects had moderate to severe obstructive sleep apnea (respiratory disturbance indexes greater than 20), and they were treated with continuous positive airway pressure (CPAP) or an oral appliance.

Obstructive sleep apnea was associated with increasing age, male sex, seizures during sleep, and scores on the Sleep Apnea Scale, the researchers said. However, localization of the epileptogenic region and seizure frequency did not differ between the groups.

Reasons for the high prevalence rate for obstructive sleep apnea in this sample are not clear, the authors said. Sleep deprivation and sleep fragmentation resulting from apneas may also be responsible for provoking seizures, they suggested. It is also possible that the number or types of antiepileptic drugs that are prescribed may precipitate or exacerbate obstructive sleep apnea, the researchers continued. Although no significant association was found in this study, they noted that the subjects were taking a variety of medication combinations, and the sample size for any given medication was small.

Further study of sleep-disordered breathing in patients with epilepsy is needed in order to better understand the mechanisms whereby sleep disorders, and their treatment, affect seizure control, the researchers concluded.

Suggested Reading
1. Malow BA, Levy K, Maturen K, Bowes, R. Obstructive sleep apnea is common in medically refractory epilepsy patients. Neurology.2000;55:1002-1007.

A GENETIC LINK FOUND BETWEEN ALS AND FRONTOTEMPORAL DEMENTIA

A defective gene located in the chromosome 9q21-q22 region may be linked to familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, according to a report published in the October 4 JAMA.Although patients with inherited forms of ALS show a high degree of genetic heterogeneity as well as clinical diversity, studying the new locus "will likely provide insight into mechanisms of these and related neurodegenerative diseases," the researchers suggested.

The researchers conducted a genome-wide linkage analysis of families identified as having two or more individuals diagnosed with ALS. From a data set of 400 families living in Boston, the researchers identified 16 families (549 people), of whom 93 were affected with either ALS or ALS combined with frontotemporal dementia. The DNA from only 305 subjects were used in the study; many individuals were not available due to the late onset and short duration of the disease, the researchers noted. Linkage calculations were performed assuming autosomal dominant inheritance with age-dependent penetrance. The married-in members of the families were used as a representative control population. The researchers repeated the analysis in four selected families living in Chicago. Concurrent frontotemporal dementia with ALS was confirmed with behavioral observations as well as imaging and pathologic studies.

The researchers located a locus for familial ALS that arises in conjunction with frontotemporal dementia. The logarithm of odds scores in the Boston data set met "classic levels of significance," the researchers reported. The inclusion of the Chicago data, they said, generated even higher scores. "The fact that the families with linkage in the Boston data set share the unusual ALS-frontotemporal dementia phenotype strengthens our confidence in the validity of this result," they said.

The researchers have examined existing databases for possible candidate disease genes for the "new dementia-related chromosomal address." However, it remains to be seen whether loci involved in inherited ALS define sets of functionally significant, interacting genes, they said.

NR