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        High Iron Levels Linked To More Stroke Damage

        ST. PAUL, MN -- April 25, 2000 -- Stroke patients with elevated levels of iron are much more likely to experience more severe neurological symptoms and possibly increased brain damage, according to a study published in the April 25 issue of Neurology, the American Academy of Neurology's scientific journal.

        Blood ferritin -- an indicator of the total amount of iron stored in the body -- in high concentrations is believed to intensify and progress neurological problems immediately following stroke, including increased weakness, speech and orientation difficulties, and decreased levels of consciousness. Patients with progressing stroke and high ferritin concentrations also may have larger areas of the brain damaged due to stroke.

        "Patients with ferritin levels higher than 275 ng/mL are 80 percent more likely to have progressing stroke," said neurologist and the lead study author Antoni Davalos, MD, at the Hospital Universitari Doctor Josep Trueta in Girona, Spain. "Stored iron increases with age in normal people, but iron accumulation is accelerated among a small percentage of the population. For these people a diet low in iron should be recommended. Blood ferritin levels should be tested as we test cholesterol or glucose levels in patients with cardiovascular diseases or cardiovascular risk factors."

        Researchers determined ferritin concentrations in plasma and cerebrospinal fluid samples taken from 100 stroke patients within 24 hours off stroke onset. Among the 45 patients who had progressing neurological decline due to stroke, the median plasma ferritin concentration was 391 ng/mL compared to 148 ng/mL among patients who remained stable or improved. The median ferritin concentration in cerebrospinal fluid was 17.4 ng/mL among the progressing stroke patients compared to 4.8 ng/mL in those less affected.

        "High body iron stores might contribute to stroke progression by increasing the production of free radicals in brain cells and in the walls of brain microvessels," Dr. Davalos stated. "Free radicals destroy the cell components and promote other mechanisms of injury that might enlarge the damaged area of the brain, referred to as the cerebral infarct volume."

        Increased body iron stores may also cause progressing stroke by enhancing the release of glutamate, a neurotransmitter in the brain. Brain cells release glutamate as a result of stroke and glutamate triggers biochemical reactions that lead to brain cell death, including the production of free radicals in brain tissue. Measuring glutamate concentration in blood is a strong predictor of neurological deterioration or damage after stroke. About 60 percent of the patients with high ferritin levels also had high concentrations of glutamate.

        Previous studies have shown that blood ferritin concentrations do not change during the first 48 hours of stroke. Thus the researchers assume that high ferritin levels obtained in this study were not the result of the body's reaction to stroke. The 45 patients with progressing stroke also showed higher body temperatures and blood glucose concentrations. These factors have been associated with stroke worsening in other studies and, according to Dr. Davalos, are the focus of some current stroke therapies.

        "Our findings support future therapeutic studies of agents which inhibit iron's toxic effects on brain cells immediately after stroke," said Dr. Davalos. "The effect of reducing iron levels among people at risk for stroke with ferritin levels higher than 275 ng/mL should also be evaluated."

        A stroke occurs when blood flow to brain tissues is disrupted, often due to the blockage of an artery in the neck or head. Stroke patients may suffer physical impairment such as paralysis, disruptions with speech, language and vision, and altered mental abilities.



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