Most of the immunologic parameters, though, outside the purpose of this paper, were abnormal. However, abnormal IgG antibodies to Alternaria tenuis, Epicoccum nigrum, and Pullularia pullulans antigens, but none of the toxigenic molds found indoor were observed. Hence, there was no correlation between the toxigenic molds found indoor with the abnormal antibodies to the three toxigenic mold antigens found in the patient's serum (Table 1). IgG titers greater > 1600 found in the patient were suggestive of chronic exposure to all the three fungi.

Figure 1

Table 1: Abnormal antibodies to Alternaria tenuis, Pullularia pullulans, and Epicoccum nigrum mycotoxins mold antigens found in the patient with neuropsychological impairments. Antibodies to all other toxigenic molds were within normal values.

EEG examination showed 10 Hz posterior dominant activities, which were synchronous, symmetrical and attenuated on eye opening and eye-closure. Neither lateralized and generalized background slowing, nor spike or sharp wave discharges foci were identified. Also, hyperventilation did not alter the background rhythm. Stage I sleep was recorded and the Awake EEG was apparently normal. Her grip meter readings were L = 29; R = 30 and she was unable to hold steady against the grid. There was an evidence of tremor of the extremities. Her reflex was abnormal, and she had accommodation paresis, arthralgia/joint pain, cough, fatigue, headache, immune mechanism disorder, memory loss, mycosis, severe muscular weakness, mood swing, intolerance to alcohol, personality changes, anxiety, attention disturbances. She had speech disturbances, frequently saying the wrong word, depression, dizziness, nausea, and blurred vision.

Summary of the patient's neuropsychological performance is presented in Tables 2 and 3. Patient had average intellectual abilities, which were about what could be expected from her academic background and work role. Her working memory on the intelligence test indicated a problem with short term and immediate recall. Her memory score was significantly below other index scores, and indicated some deterioration. Her processing speed was her highest index score. Extreme anxiety and agitation was observed throughout the tests. The Luria-Nebraska evaluation indicated impairment in intellectual process, which reinforced the belief that her general functioning was within that observed in the brain damaged population and was significantly below non-brain damaged functioning.

Figure 2

Table 2: IQ measures for the patient with chronic exposures to Alternaria tenuis, Pullularia pullulans, and Epicoccum nigrum mycotoxins

She indicated a general impairment, which demonstrated that she had not compensated or adjusted appropriately for her cognitive impairment. She demonstrated a probable arithmetic learning problem and an indication of not being very academically oriented. There was specific localization of injury found. Her memory quotient was 76, which was extremely poor and indicated significant impairment. It was significantly below her intellectual abilities in general. Her scores on other memory tests were both good and poor and indicated an intermittent lapse of memory rather than a consistent problem. She was capable of learning given repetition. Hence, her impairment appeared to be more attention and concentration oriented and thus might be more of frontal, than temporal lobe of the brain in nature. However, she indicated mild frontal lobe impairment primarily with attention, concentration, mental agility and abstract reasoning. She appeared to have a major depressive affective disorder of a moderate to severe nature. She was agitated, with lagging attention and has unusual beliefs that were unconventional. She presented with difficulty concentrating and thinking. She had some unique somatic and bodily delusions and was immobilized by multiple symptoms. She had chronic relationship problems and was an underachiever for most of her life. It seemed as though she was her own worst enemy. She presented with some symptoms such as dizziness, light-headedness, which could be both medical and psychological in nature. She presented with other anxiety symptoms that gave credence to a functional diagnosis. Although it was believed that she had an early dementia and major depression of unknown etiology, pseudo-dementia was probably ruled out. Her weakness and dizziness could also be a product of molecular encephalopathy.

Figure 3

Table 3: The summary of the neuropsychological findings in the patient with chronic exposures to Alternaria tenuis, Pullularia pullulans, and Epicoccum nigrum mycotoxins [(+++) = very high; (++) = high; (+) = relatively low)].

The patient presented as a cordial and outgoing individual, well groomed, and appeared to be significantly anxious with indications of mild to moderate depression. Her thought processes appeared vague at times, and was high strung with agitation. She indicated good cohesion between ideas and thoughts and her judgment and decision-making appeared appropriate. There was an indication of short term and immediate recall problems and she appeared to have a concentration and attention deficit. She did not make connection between her emotional state and physical symptoms and appeared depressed with accompanying agitation and anxiety to warrant a psychological diagnosis.

She appeared somewhat “dazed” and disconnected during some of the testing.

The patient was probably of average intellectual abilities and had some difficulty with abstract reasoning and higher order thinking. Her visual memory and perception was hampered with mild indication of word loss. The patient may have a learning disability of a hyperactive nature and appeared impulsive and easily distracted. There was an indication of dyslexic behavior involving sequencing events in a picture story right to left instead of left to right. The mini-mental status examination yielded a mild to moderate problem thinking clearly and reasoning in a rational fashion.

The WAIS-III indicated a verbal IQ of 101 at the 53%. Her performance IQ was 104 at the 61% and her full-scale score was 102 at the 55%. There was no significant difference between the verbal and performance scores. All scores were within the average range of scores. Her highest index score was in processing speed at 108 and the 70%. Verbal comprehension was 105 at the 66%, perceptual oriental was 101 at 53% and the lowest was working memory at 92 and the 30%. Her working memory was significantly lower than other index scores and indicates a problem with short term and immediate recall. The working memory score is significantly below other index scores. The average scaled score is 10. The patient scored 103 on verbal and 10.6 on performance. Both scores are at or slightly above the national average. Her IQ scores are about what could be expected given her academic background and occupational track.

The patient indicated her scores discriminate between brain damaged and non-brain damaged individuals. Generally her score fell within the brain damaged category. It is heavily influenced by left hemisphere activity. She generally performed below those without brain damage. However, her performance supported the MRI observation of a possible damage to the parietal lobe or frontal lobe of the brain.

The Wechsler Memory Scales indicated a memory quotient of 76. This is extremely poor and indicates a score within the borderline category. This score is significantly below her intellectual abilities and thus indicates a cognitive impairment. She indicates problems with mental control, logical memory, digit span, and visual memory. The Rey Verbal Learning Test indicated no impairment in auditory learning. Her scores were all average in immediate and short-term verbal recall. Her digits span scores indicated a problem with attention and concentration. Her short term and immediate recall was appropriate. Her letter-number score on the WAIS was significantly above the norm. This is both an immediate recall and attention measure. The patient indicated significant intermittent problems with short-term memory and in particular attention and concentration. She does perform significantly better with repetition and thus is capable of learning new material with repetition. She indicated significant attention and concentration difficulties.

The Trail making B Test indicated multiple errors involving mental agility and planning. Her score of 70 seconds indicated a minimal impairment and confusion involving right hemisphere activity. The Stroop test indicated no impairment of a language nature involving mental agility. This was a left hemisphere task. The similarities score on the WAIS indicated a score above the national average. The matrix reasoning score was slightly above the national average. There was an indication of attention and concentration problem. The Test of Proverbs indicated a mild impairment in abstract reasoning. She indicated a mild impairment of the frontal lobe primarily with attention and concentration, mental agility and abstract reasoning.

The Beck Scale indicated moderately depressed individual. She felt sad, discouraged and had a sense of failure. She did not enjoy things like she used to and had become annoyed and irritated much more easily. Her decision-making skills had suffered and she got tired much more easily now. She lacked a drive and motivation. She indicated some feelings of dizziness and light-headedness frequently. She was jumpy and had a fear of dying. She felt a weakness and was unable to relax. She was highly nervous. The MMPI indicated a significant psychological disorder in the form of agitation, lagging attention in the midst of crisis. She has unusual beliefs and is alienated and unconventional. She had identity confusion and had difficulty with concentration and thinking. She overemphasized pathology and was cynical. She possessed some unique bodily or somatic delusions and was immobilized by multiple symptoms. She had problems with authority and might have had recurrent work and family problems. She had a history of underachievement and relationship problems. She probably was insecure, anxious, a worrier and was indecisive. She was an exhibitionist. Her behavior appeared to be functional or psychological in nature rather than attributed to primary organic concerns.

Alternaria tenuis occurring in isolates from tomato, and polished rice produces tenuazonic acid mycotoxin with two isomeric forms namely: standard tenuazonic acid and isotenuazonic acid. Some species of toxigenic Alternaria tenuis produce alternariol (AOH), alternariol methyl ether (AME),₁₀and tenuazonic acid mycotoxins, and it was shown that small amounts of tenuazonic acid have pronounced mutagenic activity. ₈,₉

Pullularia pullulans lack mutagenic and or carcinogenic potential, therefore, lack significant toxicological activity, ₁₁,₁₂,₁₃ even though, acute exogenous allergic alveolitis with the typical symptoms of unproductive cough, dyspnoea on exertion, fever, weight loss, headache, and limb pains was observed in a 24-year-old bank employee.₁₂Also, pullulans have been implicated in leucocytosis, hypoxemia, and marked restrictive ventilatory defects.₁₃Kimoto et al. ₁₁found no indications of an adverse effect of pullulans on hematology and clinical chemistry values of treated animals and there was no indication of pullulan-related toxicity in terminal organ and body weights.

Epicoccum nigrum synthesizes extracellular fungal polysaccharide, called epiglucan.₁₄ The Epicoccum nigrum extracts used in allergy disorders exhibit batch-to-batch variations in protein composition and allergenic potency.₁₅ Ambivalently, Epicoccum nigrum was obtained consistently from four patients who were having allergic fungal sinusitis (AFS), indicating that E. nigrum can colonize nasal sinuses and cause AFS, ₁₆ and that EN is a significant allergen in urban communities. ₁₇However, Epicoccum nigrum has antibiotic properties (e.g., epicorazine A), hence, was found to exhibit an activity against Staphylococcus aureus.₁₈,₁₉,₂₀

The question here is, which toxigenic mold antigen was responsible for the patient's condition? It is rather difficult to say with greater confidence without further experimental evaluation of the physiological and toxicological effects of these antigens. However, from the background literature that was stated thus far, it appeared that each of these antigens must have contributed in different measures, to the patient's conditions. Considering the structural and functional groups in the metabolites of the three toxigenic molds, one would suggest that Alternaria tenuis probably has the most damaging effects since it exhibits mutagenicity and carcinogenicity. Pullularia pullulans, on the other hand, no such effects besides allergenicity, which was the patient's main health problem. Epicoccum negrum produces metabolites that are more of antibiotics than mycotoxins. Therefore, it is more likely that Alternaria tenuis may have major contributory psychological effects than the other two toxigenic molds.

It is true that the human brain has the ability to maintain its normal function even when the mind is placed under a severe physical pain. However, if the brain is anatomically damaged, such an endowment is compromised and the individual becomes susceptible to psychological changes. It is possible therefore that the time sequence of events that led to the patient's psychological conditions probably began with the chronic toxigenic mold antigens in the serum that in turn, led to the changes in the brain structure consequent upon which the mind and behavior were affected.