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VISUAL CONTRAST SENSITIVITY: A SENSITIVE INDICATOR OF NEUROTOXICITY FOR RISK ASSESSMENT AND CLINICAL APPLICATIONS.
Citation:
Hudnell, K., D E. House, AND R. Shoemaker. VISUAL CONTRAST SENSITIVITY: A SENSITIVE INDICATOR OF NEUROTOXICITY FOR RISK ASSESSMENT AND CLINICAL APPLICATIONS. Presented at 5th International Conference on Bioaerosols, Fungi, Bacteria, Mycotoxins and Human Health, Saratoga Spring, NY, 9/10-12/03.
Description:
Both human-health risk assessments of adverse effects from chronic, environmental exposures to neurotoxics and clinical practice are in need of objective indicators sensitive to the early stages of disruption in neurologic function; risk assessment for the purposes of hazard identification and risk characterization, and clinical practice for early diagnosis and intervention. Measures of visual system function appear to be well suited as early indicators for two reasons: 1) the retina, in which visual information processing begins, is a microcosm of the brain that is less well protected from environmental exposures than the brain itself and; 2) unlike cognitive and other neurologic processes, the visual system has relatively few functional outputs that can be readily quantified. Visual contrast sensitivity (VCS), an indicator of visual pattern detection ability, measures the least amount of contrast (threshold) in space defined by sinusoidal luminance modulation that is needed for an observer to detect a bar pattern. VCS is measured at five spatial frequencies (large to small bars) because different physiologic processes underlie perception at different spatial frequencies, and the processes are differentially susceptible to disruption by neurotoxics. In the presence of normal visual acuity, human studies have associated irreversible mid-to-high spatial frequency VCS deficits with methyl mercury exposure, and low-to-mid spatial frequency deficits with elemental mercury exposure. Chronic exposures to various organic solvents produced irreversible VCS deficits that were largest at mid-spatial frequency. Our recent study of apartment residents exposed to the dry cleaning solvent, perchloroethylene, observed VCS deficits at exposure levels below those at which any adverse affect had been reported previously. These data may be useful in helping to determine safe exposure levels. In the clinical setting, large VCS deficits greatest at mid-spatial frequency were associated with exposure to estuaries inhabited by the toxigenic, fish-killing dinoflagellate, Pfiesteria sp. Deficit onset occurred rapidly, within 12-48 hours after estuarine exposure, in association with multiple-system symptoms. Treatment with cholestyramine, a non-absorbable anion-exchange resin capable of binding toxins from bile, resulted in rapid symptom resolution and VCS recovery. Evidence suggested that biotoxin exposure may have triggered a proinflammatory cytokine response, resulting in inflammation, restricted blood flow in retinal microvasculature, VCS deficits and symptoms. Shoemaker's data suggest that this paradigm may generalize to illnesses caused by other toxigenic organisms, including fungi and bacteria found in the indoor air of water damaged buildings. VCS measurements, when accompanied by a comprehensive assessment of potentially confounding factors, provide an objective indication of neurotoxicity in illnesses otherwise defined by non-specific symptoms, thereby assisting in illness diagnosis and monitoring. VCS data, therefore, provide sensitive indications of neurotoxicity in both population and individual assessments by measuring the threshold level of function in a specific and uniquely susceptible neurologic pathway.