Psychological, neuropsychological, and electrocortical effects of mixed mold exposure
NEUROTOXICITY can cause irreversible nervous system damage related to cell death or permanent alterations of cell structure and receptor sensitivity. Clinical signs are classified as organi/c mental impairments, seizures, movement disorders, involvement of cranial nerves or spinal peripheral nerves, and neuromuscular dysfunction. (1) Neurotoxic exposure and injury are assessed by careful neurological and neuropsychological evaluation, complemented with functional imaging of the brain.
Occupants of mold-infested structures develop multiorgan symptoms that involve the upper and lower respiratory systems, central and peripheral nervous systems, skin, gastrointestinal tract, connective tissue, immune system, and musculoskeletal system. (2-18) Complaints of neurocognitive dysfunction are prevalent among the symptoms reported. (2,3,18-22) A large body of literature exists on the effects of various neurotoxins on neuropsychological functioning, including cognitive impairment. (23) However, only 4 studies have reported measurements of neurobehavioral changes related to mold and mycotoxin exposure. (18,20-22) The changes described include impairments in balance, reaction time, cognition, verbal learning, recall, visual spatial learning, memory, attention/concentration, and set shifting.
Only a few complementary neuroimaging studies have been published in regard to assessment of the effects of mixed mold exposure on the central nervous system. Adolescents with suspected acoustic mycotic neuroma resulting from environmental exposure to toxic molds had abnormal brainstem evoked potentials. (2) In another study, abnormal electroencephalogram (EEG) examinations in 7 of 10 patients exposed to toxic mold were reported. All 10 patients had frontal-temporal theta wave activity, which indicated diffuse changes characteristic of metabolic encephalopathy. Abnormal brainstem auditory evoked potentials were demonstrated in 9 of these patients, and 4 of the 10 patients showed clear abnormalities.
All of the patients in the current study reported wide-ranging symptoms, including headache, dizziness, visual changes, cognitive impairment, and emotional dysregulation. Their illness has been defined as "mixed mold mycotoxicosis." (19)
It is likely that studies of mold-induced neurotoxicity will yield findings similar to other studies of neurotoxicity from other causes. Single photon emission computed tomography (SPECT) has been used to complement and define the effects of toxic exposure on the central nervous system. A review of the literature on the use of SPECT scans following neurotoxic exposure confirmed that abnormalities can exist from months to years after exposure has ceased, and can involve asymmetrical abnormalities with hypoperfusion in the frontal, parietal, and temporal lobes. (24) Moreover, in 33 workers with encephalopathy following toxic exposure, 94% had abnormal SPECT scans. The most frequent areas of abnormality were the temporal lobes (67.7%), frontal lobes (61.3%), basal ganglia (45.2%), thalamus (29.0%), parietal lobes (12.9%), and motor strip (9.7%). (25)
In recognition of the complexity of health problems associated with mixed mold exposure, a multicenter investigation of patients with chronic health complaints from mold exposure was undertaken. We used generally accepted, standardized, detailed health and environmental history questionnaires, environmental monitoring data, physical examination, accepted pulmonary function testing protocols, routine clinical chemistry, standardized measures of specific immune markers (T, B, and natural killer [NK] cells), measures of antibodies to molds, neuropsychological testing, and 19-channel quantitative EEG (QEEG). The results of this project are being reported in a series of papers. The study presented herein was conducted to assess the psychological, neuropsychological, and electrocortical effects of mixed toxic mold exposure.
Materials and Method
Patients. Adult patients (N = 182) with a history of exposure to mixed colonies of molds and their associated mycotoxins (confirmed with environmental and serologic testing) as a result of structural water intrusion in residential, workplace, or school-based settings, (19) were included in this multicenter study of data gathered from chart review. All patients had been referred for evaluation of health problems related to toxic mold exposure. Because of the prominence of neurological symptoms and complaints of cognitive dissonance, patient assessments included the following neuropsychological and neurophysiological evaluations: a structured psychometric symptom checklist, neuropsychological testing, and QEEGs. The patients (age 42.7 [+ or -] 16 yr [mean [+ or -] standard deviation]) were evaluated from September 1999 through June 2003. The group comprised 126 females (age 39.3 [+ or -] 18.1 yr) and 83 males (age 36.6 [+ or -] 21.1 yr). All of the patients were evaluated for this study. Test results were compared against a national normative database in all cases. Inasmuch as our study was based on data from chart reviews, the numbers of subjects for each measure varied slightly.
Measures of psychological distress. Each patient was evaluated with a standard clinical interview and a psychometric self-report symptom inventory--the Symptom Checklist 90-R (SCL-90-R). (26) Patients rated each item on a 5-point scale of distress, ranging from not at all distressed (0) to extremely distressed (5). Their ratings were computer-scored and produced normalized t scores for 9 symptom dimensions (i.e., Somatization, Obsessive-Compulsive, Interpersonal Sensitivity, Depression, Anxiety, Hostility, Phobic Anxiety, Paranoid Ideation, and Psychoticism) and 3 global indices (i.e., Global Severity Index, Positive Symptom Distress Index, and Positive Symptom Total). For comparison, we used an adult nonpsychiatric patient normative database because it best represented the individuals examined in this study.
Neuropsychological testing. We selected neuropsychological tests on the basis of specific patient complaints, clinical efficiency, and time constraints. All tests chosen had appropriate and comparable norms for adults and children. To obtain estimates of premorbid and general intellectual functioning for all patients, we administered the Vocabulary subtest from the Wechsler Adult Intelligence Scale, 3rd ed. (WAIS-III) and/or from the Wechsler Abbreviated Scale of Intelligence (WASI). (27)
Three subtests from the WAIS-III were administered. The Digit Span subtest measures attention and working memory capacity. The Digit Symbol Coding subtest measures visual motor learning and psychomotor speed. The Symbol Search subtest is an indicator of visual scanning and concentration.
Two subtests from the Delis-Kaplan Executive Function System (D-KEFS) were selected to measure executive or higher-level cognitive functions. (28) The D-KEFS Color-Word Test produces baseline measures of color naming and word reading to compare with executive measures of inhibition and inhibition switching. The D-KEFS Trail Making Test provides baseline measures of visual scanning, number sequencing, letter sequencing, and motor speed, as well as an executive measure of number-letter switching.
The Integrated Visual and Auditory Continuous Performance Test (IVA-CPT) is a computerized test designed to evaluate auditory and visual attention over time. (29) The IVA-CPT produces global composite scores consisting of a Response Control Quotient (a positive way to describe the problem of response inhibition) and an Attention Quotient (a positive way to describe problems of inattention, loss of focus, and slow processing speed). Resulting measures are normed with a mean of 100 and a standard deviation of 15.
QEEG. Brain electrical activity was recorded from 19 cortical positions in accordance with the International 10/20 electrode-placement system, using a Lexicor Neurosearch Digital EEG acquisition system (Lexicor Research Center [Boulder, Colorado]). Electrodes were positioned on the scalp using appropriately sized electrocaps. We used impedance measurements for each cortical site to ensure accurate data collection. The raw data were edited for artifacts and then subjected to quantitative and neurometric analyses of amplitude, power, and mean frequency, using the NxLink database. (30-32) (The NxLink database has received a 510(k) clearance from the FDA [July 1998, #K974748], indicating that construction of the database was scrutinized for good manufacturing practices, and signifying the legitimacy of marketing claims made concerning the database.)