Neuropsychologic testing versus visual contrast sensitivity in diagnosing PEAS. (Correspondence).

I would like to comment on Hudnell and Shoemaker's response (Hudnell and Shoemaker 2002) to our letter (Swinker and Burke 2002), both published in the March 2002 issue of EHP.

In their letter Hudnell and Shoemaker (2002) asserted that "neuropsychologic test deficits are nonspecific." In the hands of trained neuropsychologists, specific areas of functional deficits can be identified. Attention, executive function, short-term memory, mood, adjustment, and verbal or visual fluency can be specifically assessed. Convergent validity can be established by evaluating functioning in a number of ways, that is, different test instruments that measure the same thing. Neuropsychologic deficits of a specific nature with characteristic patterns have been found in response to certain environmental exposures. The use of neuropsychologic testing has been validated in a variety of clinical settings and is not in dispute.

Memory problems have been the most unique and significant symptoms reported following Pfiesteria exposure in both the laboratory setting (Glasgow et al. 1995) and in the 1997 Maryland environmental cohort (Grattan et al. 1998). This memory deficit was objectified and quantified in Maryland by use of neuropsychologic testing. Significant abnormalities were observed on three specific tests; the Rey Auditory Verbal Learning Test was the most consistently and significantly affected. Other tests batteries, which measured other neuropsychologic functions, were not affected in the same way. Therefore, the Maryland neuropsychologic findings were specific. The deficits were not global. Their subjects' complaints did correlate with the specific test performance observed.

Use of visual contrast sensitivity (VCS) testing in lieu of neuropsychologic testing in the context of possible estuary associated syndrome (PEAS) is very much in dispute. Shoemaker and Hudnell (2001) offer no evidence to support their assertion that VCS can be used in place of neuropsychologic testing in the evaluation of PEAS. Until the VCS test is validated in direct comparison to the neuropsychologic testing that has been demonstrated to be sensitive to PEAS, advocacy of the test remains in the realm of speculation.

Other authors have echoed our reservations about the use of VCS over the past year. According to Rubin et al. (2001),

   VCS testing is controversial because abnormal
   findings are not toxin-specific and abnormal
   findings can be interpreted only cautiously
   unless accompanied by other fairly extensive
   visual tests.

Morris (2001) also commented that

   Data supporting use of the test in this setting
   are weak. Visual contrast sensitivity is affected
   by underlying eye disorders, including corneal
   and lens disorders (i.e., the effect on the contrast
   sensitivity function is optical), as well as retinal
   and optic nerve disorders. As the individuals
   most likely to experience possible Pfiesteria toxin
   exposure are those individuals spending significant
   amounts of time on the water, there is a
   heightened probability of ultraviolet exposure-associated
   eye disease, such as lenticular opacity
   and age-related macular degeneration. Thus, a
   positive screening test for impaired contrast sensitivity
   may simply reflect the environmental/
   occupational context for the tested individual.
   There is clearly a need for further research in
   this area.

Whether all the hotline callers in our 1997 study (Swinker et al. 2001) are considered exposed or unexposed depends on whether the estuary associated syndrome criteria for 1997 [Centers for Disease Control and Prevention (CDC) 1997] or the more liberal criteria from 1999 (CDC 1999) are used. Since PEAS is the current appellation and the one that Hudnell and Shoemaker discuss (Shoemaker and Hudnell 2001), then all the hotline callers should remain grouped together because they are all "exposed" under the PEAS criteria. The current PEAS case description includes the stipulation that "a health care provider cannot identify another cause for the symptoms" (CDC 1999). This type of analysis was included in our work as an accepted--and expected--research practice. [A similar process of analysis was also done in the original Maryland work, where cases were defined based on documented exposure to estuary waters and abnormal performance on neuropsychologic testing that could not be explained otherwise (Grattan et al. 1998).] Our hotline callers with neuropsychologic test impairment had a variety of well-accepted medical explanations for their symptoms or test performances; there was no need or justification to postulate a new syndrome (Swinker et al. 2001). They had no unique or consistent pattern of abnormality on the Rey Auditory Verbal Learning Test or any other test battery. Their performance was affected across a variety of functional areas, not in a single area. The neuropsychologic test performances of the callers as a group and of their asymptomatic controls were similar (Swinker et al. 2001). Thus we have not "dismissed the diagnoses of estuary-associated syndrome" (Hudnell and Shoemaker 2002). We have subjected the data to scientific analysis before forming our conclusions.

Hudnell's VCS data (Hudnell and Shoemaker 2002) suggest that the performance of the hotline control group (10 persons without symptoms) in our original work (Swinker et al. 2001) was also abnormal. This finding suggests that VCS deficits may be highly prevalent and so nonspecific as to be of limited value as a diagnostic test. VCS is affected by many factors: chemical exposures (e.g., mercury or solvents), congenital conditions (e.g., dyslexia or other learning disabilities), degenerative conditions (e.g., Parkinson's disease and multiple sclerosis), ocular disease (e.g., glaucoma or macular degeneration), other conditions [e.g., AIDS or cystic fibrosis (Hudnell 1998)], and the use of alcohol or medications (e.g., antiepilepsy drugs).

Assessment of hydrogen sulfide exposure in estuary fishermen was included in a multi-year longitudinal cohort study recently conducted in North Carolina (Moe et al. 2001). VCS and neuropsychologic testing were also systematically performed at regular intervals as part of this investigation. The data analysis phase of this effort has just begun. We should soon know more about the frequency of hydrogen sulfide exposure in estuary watermen as well as any relationship or correlation between VCS and neuropsychologic test performance in watermen over the seasons and the years.

Finally, subsequent to the CDC report (CDC 2000) quoted in my letter (Swinker and Burke 2002), the state of Maryland has verified five PEAS cases in their ongoing surveillance, as noted by Hudnell and Shoemaker (2002). These cases have been reported to the CDC (Backer et al. 2001) with little fanfare and detailing some methodologic concerns regarding exposure assessment. I do not know whether any of Hudnell and Shoemaker's cases are included in those five cases.

Marian Swinker
East Carolina University School of Medicine
Greenville, North Carolina
E-mail: [e-mail]

REFERENCES

Backer LC, Niskar AS, Rubin C, Blindauer K, Christianson D, Naeher L, Rogers HS. 2001. Environmental public health surveillance: possible estuary-associated syndrome. Environ Health Perspect 109(suppl 5):797-801.

Centers for Disease Control and Prevention (CDC). 1997. Results of the Public Health Response to Pfiesteria Workshop--Atlanta, Georgia, September 29-30, 1997. MMWR Morb Mortal Wkly Rep 46:951-952.

--. 1999. Possible estuary-associated syndrome. MMWR Morb Mortal Wkly Rep 48:381-382.

--. 2000. Surveillance for possible estuary-associated syndrome--six states, 1998-1999. MMWR Morb Mortal Wkly Rep 49:372-374. Glasgow H, Schmechel D, Tester P, Rublee P. 1995. Insidious effects of a toxic estuarine dinoflagellate on fish survival and human health. J Toxicol Environ Health 46:501-522.

Grattan L, Oldach D, Perl TM, Lowitt MH, Matuszak DL, Dicson C, et al. 1998. Learning and memory difficulties after environmental exposure to waterways containing toxin-producing Pfiesteria or Pfiesteria-like dinoflagellates. Lancet 352:532-539.

Hudnell HK, Shoemaker RC. 2002. Visual contrast sensitivity: response [Letter]. Environ Health Perspect 110:A121-A123.

Hudnell K. 1998. Human Visual Function in the North Carolina Clinical Study on Pfiesteria piscicida. EPA 600-R98-132. Research Triangle Park, NC:U.S. Environmental Protection Agency.

Moe C, Turf E, Oldach D, Bell P, Hutton S, Savitz D, et al. 2001. Cohort studies of health effects among people exposed to estuarine waters: North Carolina, Virginia, and Maryland. Environ Health Perspect 109(suppl 5):781-786.

Morris JG. 2001. Human health effects and Pfiesteria exposure: a synthesis of available clinical data. Environ Health Perspect 109(suppl 5):787-790.

Rubin C, McGeehin M, Holmes A, Backer L, Burrison G, Earley M, et al. 2001. Emerging areas of research reported during the CDC National Conference on Pfiesteria: From Biology to Public Health. Environ Health Perspect 109(suppl 5):633-637.

Shoemaker RC, Hudnell HK. 2001. Possible estuary-associated syndrome: symptoms, vision, and treatment. Environ Health Perspect 109:539-545.

Swinker M, Burke W. 2002. Visual contrast sensitivity as a diagnostic tool [Letter]. Environ Health Perspect 110:A120-A121.

Swinker M, Koltai D, Wilkins J, Stopford W. 2001. Is there an estuary-associated syndrome in North Carolina? Findings in a series of hotline callers. NC Med J 12:126-132.