PROCEEDINGS of the Int. Conf. - Mycotoxins and Neurotoxicity - CFS

[Guest guest]

PROCEEDINGS of the International Conference

Saratoga Springs, New York

Oct 6-7, 1994

FUNGI AND BACTERIA IN INDOOR AIR ENVIRONMENTS

Health Effects, Detection and Remediation

Editors

Eckardt Johanning, M.D.,M.Sc.

Chin S. Yang, Ph.D.

Eastern New York Occupational Health Program

MYCOTOXINS AND NEUROTOXICITY

Page 161

Pierre L. Auger, M.D. M.Sc., FRCPC©

Abstract: Mycotoxins have been called " agents in search of a disease "

(Schiefer, 1990). Medical literature contains little information

concerning airborne mycotoxins.

We would like to make the point that mycotoxins are potent neurotoxic

agents.

Chronic Fatigue Syndrome and psycho-organic syndrome comprise an

array of symptoms which overlap.

We considered both of these diseases as consequences of possible

central nervous system injuries and hypothetically related to

mycotoxin exposure.

Key words. Mycotoxins, neurotoxicity, Stachybotrys atra, indoor air

pollution, chronic fatigue syndrome, psycho-organic syndrome.

INTRODUCTION

Fungi are one of the agents present in dust causing harm to human

health. The lung and upper respiratory airways have been considered

to be the historical targets for disease subsequent to mold exposure.

Mycotoxins are metabolites produced by fungi in certain favorable

environment. They are polysystemic poisons and many of them are

neurotoxic and immunotoxic. Since 1984, we have been confronted with

patients complaining of fatigue, cognitive difficulties, repetitive

respiratory infectious diseases and a complex array of symptoms

consistent with the diagnosis of psychoorganic syndrome (POS) and/or

chronic fatigue syndrome with immunodysfunction (CFIDS).

We think that neurotoxicity from mycotoxins are an important aspect

of mycotoxicosis.

This report is based on soft data, on circumstantial evidence.

Epidemiological analysis is not yet possible.

SUMMARY OF TOXIC EPISODES INVESTIGATIONS IN VARIOUS BUILDING SETTINGS

1984-1994

Hospital* (*Mainville, 1988)

Medical assessment was carried out according to standard criteria

for clinical evaluation.

Chronic fatigue syndrome was defined by recognized signs (NIH

Publication, 1990).

One hundred sixteen (116) case summaries were forwarded to us.

The main complaints were extreme fatigue and severe cognitive

symtpoms.

Fifty (50) were more thoroughly evaluated. They were:

nurses

29

patient attendants

15

secretaries

3

physiotherapist

1

occupational therapist 1

record

keeper 1

The symptoms were:

Extreme fatigue at one point in time 100%

Neurocognitive problems 90%

Chronic sore

throat 78%

Muscle soreness and/or weakness 74%

Frequent upper airways infections 50%

Routine hematological and biochemical findings were not specific.

Multiple air and surface samplings yielded by order of importance:

Stachybotrys atra

Aspergillus niger

A. Versicolor

A. Clavatus

A. Ochraceus

Penicillium brevicocompactum

P. Cyclopium

Paecilomyces varioti

Alleviation of symptoms after decontamination among 22 available for

follow-up:

2 had not recovered

2 felt slightly better

13 felt 80% to 100% improved

3 felt symptoms were stress-related

2 now had another diagnosis

Various Dwellings/Offices; Symptoms Relieved Upon Removal Of Moldy

Material Or From The Setting.

~ Husband and wife: extreme fatigue, hacking cough and cognitive

symptoms

~ Mother and 2 children: multiple respiratory infections, asthma,

headache, fatigue

~ 11 civil servants: in one office

5 with sick building syndrome

3 with chronic fatigue syndrome

~ Wife, husband, child with chronic fatigue syndrome with

Penicillium Brevicompactum

~ Similar cases published recently with Trichoderma viridae,

Penicillium frequentens, P. cyclopium, Phoma

species

Harbour Station

Medical evaluation was conducted by three physicians, one of whom

is a neurologist. Neuropsychological testing were supervised by a

neuropsychologist. Measurements of formaldehyde and stoddard solvent

were conducted by an industrial hygienist as recommended in " Le guide

d' 'echantillonage de l'air on milieu de travail du Quebec 9 edition

aout 1990 " . Measurements and identification were done by a

mycologist.

This 50-years-old two-story building with opening windows was free

of formaldehyde and Stoddard solvent.

The crawl space had often been flooded.

There were three occupants working in this building complaining of

headaches, fatigue, sinusitis, problems of memory and intellectual

concentration.

Two occupants underwent more complete medical work-up three months

after removal from exposure.

The findings are summarized in Table 1.

Aspergillus fumgatus, A. niger were detected in the sub-basement and

crawl space, and Penicillium aurentiogriseum in the dwelling of the

male worker.

Table 1.

Male Director, 42 Years Old

Complaints:

Fatigue, irritability, cognitive symptoms, worst in fall and

winter.

Physical examination.

Negative

Laboratory

Immunology: Elevated CD4/CD8 RATIO

Neuropsychological testing: Visual spatial anomaly, Type2

b encephalopathy

Female Secretary, 34 Years Old

Complaints:

Fatigue, headaches, cognitive symptoms, muscle soreness,

recent asthma, worst in fall and winter

Physical examination:

Carpal tunnel and thoracic outlet syndrome

Laboratory:

Immunology: Elevated CD4/CD8 RATIO, Elevated IgM.

Neuropsychological testing: decreased cognition functions.

Type 2 b Encephalopathy.

Sub.Chapt: CHRONIC FATIGUE SYNDROME

Chronic Fatigue Syndrome is a term recently coined for a long-known

condition characterized by extreme fatigue accompanied by a

polysystemic symptomology: sore throat, headache and neurocognitive

complaint.

In 1988, clinical criteria were devised to help conduct

epidemiological studies (NIH Publication, 1990). See Table II.

Table II. *Chronic Fatigue Syndrome: A Working Case Definition.

Major Criteria

1. -Onset of persistent or relapsing fatigue severe enough to reduce

average daily activity below 50%

2..-Absence of other conditions producing similar symptoms

Minor Criteria

Symptoms

1. -Mild Fever

2.-Sore throat

3.-Painful lymph nodes

4.-Muscle weakness

5.-Myalgia

6.-Fatigue after mild exercise

7.-Headaches

8.-Arthalgia

9.Neuropsychological complaints

10.-Sleep disturbances

11.-Abrupt appearance

Physical criteria

1.-Low fever

2.-Pharyngitis

3.-Tender small lymph nodes

Diagnosis

2 major criteria, and 8 clinical symptoms or 6 clinical symptoms and

2 physical signs

It must be pointed out that intoxication to heavy metals, pesticides

and solvents have to be ruled out before the diagnosis of chronic

fatigue syndrome may be invoked. Therefore it is easy to realize that

clinical pictures of toxic encephalopathy and chronic fatigue

syndrome vastly overlap.

PERTINENT MEDICAL LITERATURE

There exist a number of different mycotoxins for which we have no

data about their toxicity. Trichothecenes have been the object of

more thorough laboratory testing. We know that they exhibit their

toxicity through DNA and RNA synthesis inhibition. The brain and

immmunological systems are therefore sensitive organs to these

poisons (Feuerstein G., et al 1989).

A considerable number of other fungal metabolites exist from which

we have gathered few data. Preliminary results seem to unravel

general and neurological toxics effects in many of them ( D.

H., 1982). In Table III, it is possible to compare the acute

neurotoxics effects of well-known agents compared to the only

trichothecene studied in human (DAS).

Table III. Comparative Scale of Solvents and Mycotoxins Associated

With Human Neurotoxicity.

Known Human Neurotoxics'

Toluene: 65 mg/kilos (Inh-8hrs man)

Xylene: 74 mg/kilos (Inh-8hrs man)

Stryrene: 37 mg/kilos (Inh-8hrs man)

Trichothecene In Man

DAS; 0.09mg/kilo (i.v. -rapid-70 kilos man)

0.26mg/kilo

A few case reports are gleaned from the medical literature. They

can let us suspect the importance of the neurotoxic effects of molds.

Croft W. et al (1986), Johanning, et al (1993), and Recco P., et al

(1986) described patients exposed to Stachybotrys Atra. These people

all complained of neuropsychological problems accompanied by fatigue

with concommitant irritative symptoms. Nexo, et al (1983) relate

cases of extreme fatigue alleviated by the removal of dusty carpets

possibly contaminated by known toxicogenic Fusarium fungi.

Two other publications seem to entertain a similar hypothesis

(Leving P.H., et al 1992, Chester A.C. et al, 1994). They described

cases of chronic fatigue syndrome in buildings with indoor air

problems. Also a few epidemiological studies of other symptoms than

respiratory have shown significant relative risks of exposure to

molds and humidity giving rise to symptoms like depression, aching

joints, nausea, tiredness (Waegermaekers M., et al 1989, Platt, et al

1989). Finally Gordon et al (1993) reported a neurological syndrome

in a young man consisting of dementia and tremor possibly related to

the presence of different toxicogenic Aspergillus and Penicillium in

a moldy silage.

References: deleted for brevity

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Dr Marinkovich gave me his personal copy of the PROCEEDINGS

manual in 1999 after I told him that I was a participant in the 1988

Holmes et al " CFS definition study group " to define the CFS syndrome.

-MW

Mold Warriors by Dr Ritchie Shoemaker

Chapt. 23: " Mold at Ground Zero for Chronic Fatigue Syndrome " .