Chronic Neurotoxicity From Chronic Mold Exposure

Singer, R. (2011). Chronic neurotoxicity after chronic mold exposure. Presented at the 50th Annual Meeting of the Society of Toxicology, Washington, March 7th.


Chronic Neurotoxicity after
Chronic Mold Exposure

Raymond Singer, Ph.D.

Board-Certified Neuropsychologist

Santa Fe, New Mexico, and
New York, New York

Rationale: The products of repeated indoor water intrusions, as well as their distribution cycles, are complex. Toxic products include mold parts (fungi contain glucan - a polyglucose compound - in the cell wall, which can induce a defect in macrophage control of other inflammatory cell types at very low levels of exposure; hyphae); neurotoxic volatile organic hydrocarbons (Toxicological Sciences 117(2), 418–426 (2010)); neurotoxic mycotoxins; spores, which can transmit infections; endotoxic bacteria, and possibly other substances. Their distribution will vary depending upon humidity cycles.

The products of repeated indoor water intrusions will be referred to as “mold” in this paper. There have been a number of groups studies and case reports describing the neurotoxicity of chronic exposure to mold. However, the method to diagnose mold neurotoxicity in an individual case is a developing art and science.

Objective: 1) present a method for the individual diagnose of mold neurotoxicity; 2) demonstrate that it is possible to diagnose mold neurotoxicity in an individual case.

Subject: Female, 56 years old, divorced, 3 grown children. Education: Ivy League graduate in 3 years, Magna Cum Laude and Phi Beta Kappa; MA in Economics from a highly competitive university with an A average; law degree - top ten percent of her class at top-ranked law school. Spoke 4 languages.

Employment: Unemployed following her illness. Former director, energy and software financial development companies; former deputy chief lawyer for a cabinet-level Federal department.

Exposure: Resided in a contaminated, well-known, prestigious condominium for 1.5 years. Shortly after moving into the contaminated residence, she developed flu-like symptoms with nasal congestion, burning eyes, and fatigue.

Source of Mold: The washing machine overflowed, spilling water throughout the condominium. When repairing the water damage, black mold became visible behind the baseboards along the walls. Thereafter, a series of extensive piecemeal repairs was performed.

Additional mold was discovered throughout the condominium as the repairs progressed from room to room, some due to leaks from faulty plumbing in several rooms. With each of these attempted repairs, walls were torn out without the utilization of proper abatement procedures, releasing contaminants into the air in a failed effort to fix the problems. Most of the moisture inside the walls came from roof leaks and the flood. Some leaks appeared after roofing repairs.

Various interior wall shafts were not inspected for mold, which was discovered later. The contents of the apartment were not properly protected. Without such protection, the contents were exposed to harmful contaminants and other particulate matter. Apparently, the air vents were not adequately protected, so that airborne mold spores contaminated the unit's HVAC system.

Environmental testing: An industrial hygienist reported: The building clearly had a history of a wide range of leaks and water intrusion due to design, construction and maintenance issues, eventually leading to water damage, mold and bacterial growth, and leading to human exposure. The mold problems were compounded by conducting investigation, sampling and testing in a piecemeal manner. Unit occupants were allowed in the building while destructive testing and remediation were being conducted in some units. This inevitably led to exposures.

The mold including stachybotrys (SB) (3,424 counts of fungal structure (FS); 91,307 FS/m3, 97% of sample, categorized as massive fungal growth, with black mold in many locations in the apartment, including air samples of 260 particulates SB/M3.

Assessment approach: Comprehensive neurobehavioral toxicity evaluations were performed on 5 occasions two-seven years post-exposure. The assessment included extensive diagnostic interviews, administration of tests which have established normative bases and which are known to be sensitive to neurotoxicity, tests for effort, malingering, distortion, hypochondria, and record review (exposure, medical).

Findings:

Current symptoms: The subject reported the following current symptoms:

Severe cognitive problems
Short term memory loss
Multiple chemical sensitivity (MCS)
Respiratory symptoms on exposure; asthma on extreme exposures
Visual disturbance MCS symptom
Reduced sensation in extremities
Weakness in left hand
Joint pain
Headaches
Sleep Disorder: Sleeps up to 16 hours a day and still fatigued.
Urinary frequency and swelling

The Neurotoxicity Screening Survey (included in Appendix 1) shows a symptom constellation consistent with neurotoxicity in the following categories:

Memory and Concentration
Autonomic Nervous System
Vision
Hearing
Balance
Smell-Taste
Peripheral Numbness
Sensory-Motor
Chemical Sensitivity
Emotionality

Test results:

Blood marker: SB IgE was 51 ELISA units, above the reference range of 50.

Imaging: MRI showed right temporal lobe abnormality.

Electrophysiological testing:

Visual Evoked Potentials: Impression: Visual evoked response study was abnormal bilaterally.

Somatosensory Evoked Potentials: somatosensory evoked potential responses were recorded from each lower extremity by stimulating at the ankle and by recording over the lumbar point and the contralateral sensory cortex. There is prolongation of the absolute latency on the left and borderline on the right. The amplitudes of the waveforms were decreased and poorly developed. Impression: left abnormal due to prolongation at the lumbar plexus and borderline right.

Cognitive function: See Appendix 1. Her Full Scale IQ prior to exposure was estimated to be at the 97 percentile (pct). Initial testing found WAIS-III Working Memory at the 5pct; WMS-III Working Memory 13pct; Selective Reminding Test 11 pct; Comprehensive Trail-Making Test 9pct; Stroop Color and Word Test 7 pct. These results indicate a significant decline in memory and executive function.

Results of the Neurotoxicity Screening Survey were elevated (436) and consistent with neurotoxicity, with Symptom Distortion not indicated.

Repeated testing over 5 years after being removed from exposure found overall cognitive function partially improved, but her function did not return to prior levels.

Personality testing using the NEO Personality Inventory found no significant personality disorder, and did not suggest somatisizing (hypochondria).

Medical record review found no competing explanations of his illness.

See Appendix 1 for a listing of the neurobehavioral test results.

Conclusion: Mold exposure can cause neurotoxicity, revealed by neurobehavioral evaluation, lasting many years after exposure.Appendix 1: Neurobehavioral test results as of 2008

Wechsler Adult Intelligence Scale, Third Edition: WAIS-III:
(In parentheses, under column heading percentile, from tests administered in 2003, 2 years after the exposure began)
Age - Adjusted
Scaled Scores Percentile Classification of change since 2003
Verbal Subscales
Arithmetic 5 5 (02) Some improvement, but still quite deficit
Digit Span 10 50 (16) Improvement, but still deficit for you
Letter-Number
Sequencing 13 84 (16) Improvement

Performance Subscales
Digit Symbol - Coding 9 37 (50) Decrease
Block Design 10 50 (75) Decrease
Object Assembly 10 50 Not previously administered
Object Assembly results are deficit for the subject, showing why she might be having difficulty in directions and getting lost.

Score Percentile Confidence Interval - 90%
Index Scores:
Working Memory 95 37 90 - 101
(5) Improvement

Interpretation: Overall, the subject is still showing cognitive deficits when compared with her pre-exposure level of function. Some functions mildly improved, and some functions declined. Overall memory function as measured by this test improved to the 37th percentile, however, this is still a deficit function for the subject. Mental arithmetic skills are still quite poor.

Wechsler Memory Scale, Third Edition (WMS-III):

Primary Subtests Age Scaled Score Percentile
Logical Memory I - Recall 14 91
Verbal Paired Assoc. I - Recall 10 50
Logical Memory II - Recall 11 63
Verbal Paired Assoc. II - Recall 10 50
Auditory Recognition - Delayed 15 95

Auditory Process Subtests
Logical Memory I
1st Recall Total 13 84
Learning Slope 15 95
Verbal Paired Assoc. I
1st Recall Total 11 63
Learning Slope 11 63
Logical Memory II
Percent Retention 7 25
Verbal Paired Assoc. II
Percent Retention 9 37

Confidence
Primary Index Scores Index Score Percentile Interval (90%)
Auditory Immediate 111 77 104 - 116
(47) Improvement
Auditory Delayed 102 55 94 - 110
(87) Decreased
Auditory Recog. Delayed 125 95 109 - 128
(91) Unchanged

Sum of
Auditory Process Composites Scaled Scores Percentile
Single Trial Learning 24 78
Learning Slope 26 89
Retention 17 25
Retrieval 5 97

Primary Index Differences Frequency of
Difference in
Standardization
Difference Sample
AD - ARD -23 6.9

Interpretation: Declines continue to be found in verbal memory. The primary problem appears to be difficulty in retention of learned material.

Benton Visual Retention Test (Administration B, Form C). This test assesses the ability to remember, based upon visual input. Comparison IQ = 128

Expected for IQ Observed Difference
Number correct 6 8 +2
(7)
Number errors 5 3 -2
(4)
Interpretation: Unchanged
Number Correct Score: Within Normal Limits.
Number of Errors Score: Within Normal Limits.

Benton Visual Retention Test (Administration B, Form C). This test assesses the ability to remember, based upon visual input. Comparison IQ = 128
Results as of 7/27/2004
Expected for IQ Observed Difference
Number correct 6 6 0
Number errors 5 5 0

Interpretation:
Number Correct Score: Within normal limits.
Number of Errors Score: Within normal limits.

The Booklet Category Test

Raw Score T-score Percentile
I Errors 0
II Errors 0
III Errors 4
IV Errors 1
V Errors 9
VI Errors 7
VII Errors 2
Total Errors 23 61 86

Interpretation: Within normal limits. This test was not given previously.

Comprehensive Trail-Making Test (CTMT) comprises a standardized set of five visual search and sequencing tasks that are heavily influenced by attention, concentration, resistance to distraction, and cognitive flexibility, in addition to visual search and sequencing demands. The CTMT may be useful in neuropsychological assessment generally for the purposes of detecting brain compromise... including the detection of frontal lobe deficits; problems with psychomotor speed, visual search and sequencing, and attention; and impairments in set-shifting.

Trail # Raw Score T-Score Percentile Description
1 34 55 69 Average
2 42 52 58 Average
3 53 46 35 Average
4 38 53 62 Average
5 108 39 14 Below Average
(16) Unchanged
Total 245
Composite Index 48 43
(9) Improved
Interpretation: Although there was an improvement in the composite index, in the critical trail number five, the results were unchanged.

Testing: 7/27/04

Trail # Raw Score T-Score Percentile Description
1 39 52 58 Average
2 41 53 62 Average
3 41 55 69 Average
4 31 59 82 Average
5 71 49 46 Average

Total 268
Composite Index 54 67

Interpretation: Showed some improvement compared with prior testing, and post testing.

Controlled Oral Word Association Test evaluates verbal fluency, the ability to find and use words (Benton Controlled Oral Word Association Test: Reliability and updated norms. RM Ruff et al. Archives of Clinical Neuropsychology, 11(4), 329-338, 1996).

Raw Score Correction Total Percentile Classification
31 31 -7 = 24 4.5 Deficient

Interpretation: Previously 21st percentile: decreased
Perseverations: 0

Frontal Systems Behavior Scale (FRSBE) is a rating scale designed to measure behaviors associated with damage to the frontal lobes and frontal systems of the brain.
Self Rating
T-score T-score
Before Illness % After Illness %
Apathy 52 58 94 >99
Disinhibition 71 98 71 98
Executive Dysfunction 56 73% 82 >99
Total 82 >99

Interpretation: Similar as before.

Grooved Pegboard Test evaluates manual dexterity (the ability to use hands in a sensitive and productive way). Dominant Hand:

Dominant Non-dominant
Time for completion: 100 s 88 s
Percentile: 1.4 16
Interpretation: Deficit. Similar as before. Note somatosensory evoked potential abnormalities as described in an above section of this report.

Neitz Test of Color Vision screens for color vision defects.

Number correct of 9 items: 4/9
Interpretation: Moderate Unspecified Deficiency/ Significant Tritan Deficiency

Neurotoxicity Screening Survey:

Factor Results
Score Classification
Memory and Concentration...... 104 Elevated
Autonomic Nervous System...... 71 Elevated
Vision........................ 18 Elevated
Hearing....................... 5 Within Normal Limits
Balance....................... 2 Borderline
Smell-Taste................... 6 Elevated
Peripheral Numbness........... 15 Elevated
Sensory-Motor................. 42 Elevated
Chemical Sensitivity.......... 10 Elevated
Emotionality.................. 45 Elevated
Distortion I.................. 8 Within Normal Limits
Distortion II................. 7 Within Normal Limits

Overall Neurotoxicity Indicator 318 Elevated

Interpretation: Results consistent with those of patients diagnosed with neurotoxicity.

Paced Auditory Serial Addition Test evaluates auditory information processing and tracking.

Subject was unable to perform this test, so the testing was discontinued.

Interpretation: Deficit

Ruff Figural Fluency Test measures nonverbal fluency analogous to the verbal tests that require the respondent to generate as many words as possible starting with a specific letter of the alphabet.
Error Education
Raw Ratio Correction Total Percentile Interpretation
Unique Designs 42 - 7 35 1-5% Impaired
Perseverations 7 0.175 -0.03 0.145 69% Average

Interpretation: Deficit

Selective Reminding Test evaluates the ability to learn. A list of words is read, followed by free recall. After each trial and subsequent recall, the subject is reminded of words that were missed. Twelve trials are administered.

Words continuously remembered, summed over trials (CLTR): 40
Expected: 74.1
Percentile rank for gender, age and education: 15%
Interpretation: Deficit. Previously 11%, similar.

Stroop Color and Word Test evaluates mental flexibility (45 sec administration).

Raw Age/Ed
Score Predicted Residual T-Score Percentile
Word reading: 79 113 -34 26 <1
Color naming: 60 81 -21 33 5
Color/Word: 31 46 -15 35 7
Interference: 31 35 - 4 46 35
Interpretation: Deficit - similar as in the past

Visual Search and Attention Test This test measures visual scanning and sustained attention. The measurement of attentional processes is an important element in the assessment of brain-damaged patients or individuals with suspected cognitive deficits. Attention and concentration are commonly impaired in individuals who have suffered brain damage and impairment in these abilities is often a prominent residual effect of brain damage

Left Right Total
Score 43 36 79
Percentile 25 21 22
Interpretation: Deficit - but improved

EMOTIONAL FUNCTION

Beck Anxiety Inventory measures emotional anxiety*. Score: 22
Interpretation: Moderate Anxiety (Improved)

Beck Depression Inventory measures emotional depression**. Score: 23
Interpretation: Moderate to Severe Depression (Similar)

Profile of Mood States

Raw Score T Score %
Tension 15 44 27
Depression** 18 44 27
Anger/Hostility 6 42 22
Vigor 3 40 16
Fatigue 21 60 84
Confusion/Bewilderment 20 60 84

Interpretation: Not depressed at time of testing. High levels of fatigue and confusion.

WELL-BEING MEASURES

Alcohol Use Disorders Identification Test (AUDIT) was developed by the World Health Organization to identify alcohol use disorders. Cutoff = 8

Score: 1
Interpretation: Alcohol use problems are unlikely.

Fatigue Severity Scale identifies fatigue with features that are specific to the medically ill. These features are largely independent of depressive symptoms of fatigue.

Mean score: 6.1
Interpretation: Consistent with medically ill patients - similar as in past

General Well Being Schedule evaluates general well-being compared with the population of the US.

Score: 45
0-60 Severe Distress

Human Activity Profile measures levels of physical activity.

Score Percentile
Maximum Activity Score 79 71
Adjusted Activity Score 69 33
Activity Age 51
Activity Classification Moderately Active
Dyspnea Scale 7 41
Interpretation: Within Normal Limits

Quick Environmental Exposure and Sensitivity Inventory, Version 1 (QEESI) identifies health problems respondent may experience in response to various environmental exposures.

Score Interpretation
Chemical Intolerance 89 High
Other Intolerance 58 High
Symptom Severity 71 High
Masking Index 1 Low
Life Impact 94 High

Interpretation: Very Suggestive of Multiple Chemical Intolerance. Similar as in past.

DISTORTION AND MALINGERING TESTS

Absurd responding detects a patient responding an nonsensical way.
Results: 0/3
Interpretation: Non-malingering

Dot Counting Test detects suspect test-taking efforts in adults.

Comparison Group: Mild Dementia
Mean Ungrouped Time 7.8
Mean Grouped Time 5.6
Number of errors 1
Signs of suspect effort
Does mean Grouped time exceed mean Ungrouped time by 1 sec? No
Are there counting errors on Card 6 and/or Card 12? No
E-Score (# of errors plus mean time, ungrouped and group) 15
E-Score Cutoff 22
Under test development conditions:
Sensitivity (the test’s ability to detect suspect effort) 62%
Specificity (the test’s ability to detect normal effort) 94%
Under base rate assumption of 15% population suspect effort:
Positive Predictive Accuracy
(the test’s ability to detect suspect effort) 64%
Negative Predictive Accuracy
(the test’s ability to detect normal effort) 93%

Interpretation: Normal effort

Dot Counting Test detects suspect test-taking efforts in adults. Testing: 7/27/04

Comparison Group: Mild Dementia
Mean Ungrouped Time 7.2
Mean Grouped Time 3.2
Number of errors 0
Signs of suspect effort
Does mean Grouped time exceed mean Ungrouped time by 1 sec? No
Are there counting errors on Card 6 and/or Card 12? No
E-Score (# of errors plus mean time, ungrouped and group) 11
E-Score Cutoff 22
Under test development conditions:
Sensitivity (the test’s ability to detect suspect effort) 62%
Specificity (the test’s ability to detect normal effort) 94%
Under base rate assumption of 15% population suspect effort:
Positive Predictive Accuracy
(the test’s ability to detect suspect effort) 64%
Negative Predictive Accuracy
(the test’s ability to detect normal effort) 93%

Interpretation: Normal effort

Miller Forensic Assessment of Symptoms Test (M-FAST) provides information regarding the probability that an individual is malingering psychiatric illness based on a structured interview. Administered 7/27/04. Total score cutoff = 6.
% Negative % Positive
Raw Score Prediction Prediction
Reported vs. Observed 0
Extreme Symptomatology 0
Rare Combinations 0
Unusual Hallucinations 0
Unusual Symptom Course 0
Negative Image 0
Suggestibility 0
Total 0 100% <48%

Interpretation: Honest responder

Three Word Memory Test evaluates the presence of a memory disorder. A malingering subject may remember less than 40% of the words.

Number correct: 12/12
Interpretation: Non-malingering

TOMM
Raw Score
Trial 1 48
Trial 2 50
Retention 50

Interpretation: Good effort

Recognition testing: Recognition is an easier task than recall.

Recognition test*** Results Classification
Logical Memory II 29/30 excellent effort
Verbal Paired Associates II 24/24 word pairs excellent effort
Auditory recognition - Delayed (min 43) 53 good or better effort