The Role of the Brain and Mast Cells in MCS

[Guest guest]

The Role of the Brain and Mast Cells in MCS

http://www.tldp.com/issue/210/roleoftheb.htm

by Gunnar Heuser, MD, PhD, FACP

 

 

Multiple Chemical Sensitivity (MCS) was first described in the 1980s, yet it

has remained controversial. The resistance to the concept of MCS has come from

scientists who pointed out the lack of solid scientific diagnostic tests. It

has also come from the industry which has trouble accepting the proposition

that their products make a great number of people sick.

 

My personal experience (I have evaluated several thousands of chemically

injured patients) has convinced me that MCS is based on a physiological and not

on

a psychological mechanism. This is why I have been interested in finding

objective evidence for MCS. In this paper I will present a mast cell hypothesis,

a

limbic system hypothesis, and an office approach to objective testing for

MCS.

 

 

Mast Cell Disorder and MCS

 

Patients with mastocytosis can be exquisitely sensitive to even small amounts

of chemicals. When mast cells discharge histamines and other compounds,

patients often develop flushing and a metallic taste in their mouth.

 

A few years ago I decided to test some of my patients for mast cell disease.

Some of these patients with MCS actually turned out to have mastocytosis.

Other patients were found to have a mast cell disorder.

 

All diagnoses were made on the basis of skin biopsies done in an area which

on inspection and palpation, showed no evidence of abnormality. It was also

made on the basis of an elevated tryptase (an enzyme produced by mast cells)

level. If mast cells were present in excess and/or if tryptase levels were

elevated we would make a diagnosis of mast cell disease or disorder, if the

clinical

picture was also consistent with that diagnosis. In a few patients we also

used a bone marrow biopsy to assist in the diagnosis.

 

Mastocytosis is considered to be a very rare disease. Yet, I have accumulated

more then 20 patients with that diagnosis in a matter of two to three years.

 

At this time our testing is done on a random basis. We are now developing a

protocol by which we will introduce a challenge (e.g. perfume, nail polish,

chemicals found in a carpet store, etc.) and then test at a time when the

patient

is symptomatic from that challenge.

 

We also hope to work with the Mastocytosis Society1 in further developing

diagnostic approaches to the overlapping syndromes of mastocytosis and MCS.

 

At this time the diagnosis of MCS is considered justified only in the absence

of diseases such as mastocytosis and porphyria.2 This exclusion will require

that all patients with MCS be tested for mast cell disorder and

porphyrinopathy. I believe that this indeed should be done.

 

In summary I postulate that chemical injury can trigger a mast cell disorder

which in turn can cause MCS. This concept was recently published.3

 

 

Limbic Hypermetabolism and MCS

 

Patients with MCS often show emotional instability during their reactions to

small amounts of chemicals. This has been likened to the epileptogenic effects

of kindling which is particularly effective in the limbic system of the

brain. Yet no proof of this concept has come forward to date.

 

We started doing PET brain scans on some of our patients with MCS and found

that the limbic, hypothalamic and brain stem areas are hypermetabolic (in terms

of their radioactive glucose uptakes) and therefore hyperactive (almost as

seen during focal seizure activity).

 

Since the limbic system contributes emotional reactions and interpretations

to sensory input, and since patients with amygdaloid (the amygdala is part of

the limbic system) seizures can develop panic and related attacks during an

amygdaloid seizure, our data appear to explain the emotional instability during

a

reaction to chemicals.

 

The previously mentioned structures also serve memory and cognitive as well

as neuroendocrine and autonomic nervous system functions, all of which can be

deranged in a patient with MCS.

 

In summary, I have shown that patients with MCS can develop hyperactivity in

deep structures of the brain and that this may explain their emotional

instability which therefore develops on a physiological rather than

psychological

basis.

 

It should be mentioned at this time that patients who are impaired and/or

disabled from chemical injury and resultant MCS often become depressed. This

depression would obviously be a natural reaction to their impairment and/or

disability and therefore be a secondary depression.

 

Our findings were first published in 19994 and will soon be published5 in

proceedings of a meeting on Chemical Intolerance. In this volume, kindling and

related mechanisms are also discussed.

 

 

Challenge Testing in the Medical Office

 

A few years ago, at a meeting on MCS, testing of patients in an environmental

chamber was suggested as the most scientific approach to proving MCS. This

suggestion proved impractical which is why so few publications exist which

provide a protocol for testing a patient for MCS.

 

In my office we have developed a protocol by which a patient first undergoes

baseline testing of pulmonary and immune functions as well as 24-hour urine

collection for porphyrin fractions. Then the patient voluntarily inhales (via

mouth and nose) nail polish, perfume, or exposes himself/herself to a chemical

environment. Once symptomatic from that exposure, the patient undergoes

follow-up testing of the same parameters and of course, undergoes a follow-up

physical examination with special attention to neurological abnormalities and/or

changes on auscultation of the lungs.

 

Ideally, the patient brings a non-sensitive person (age and sex matched) who

undergoes the same testing. Patient and volunteer (control) are carefully

observed by my office staff who make detailed notes.

 

Table 1 shows comparison of some immune parameters with regard to the

above-mentioned tests. So far, we have found that MCS patients indeed respond

more to

chemical exposure than their controls. This is also true of pulmonary

function which is more impaired when the patient becomes symptomatic after

exposure

to a small amount of chemicals (see table 2).

 

We addressed elevation of TA1 (CD3+CD26+) cells in an earlier publication.6

Our data on T3+ (CD3) cells are unpublished. These cells can, in my opinion, be

used as indicators of reactions to chemicals although they do not seem to

contribute to any symptomatology.

 

We are in the process of adding additional measurements (e.g. cerebral blood

flow, tryptase blood levels, and others) to our protocol. Naturally, we do

challenge testing only when the patient needs to prove MCS to Social Security,

insurance carriers (long-term disability) and the courts. We are slowly

accumulating data for future publication in a peer-reviewed journal.

 

If other interested physicians were to use our approach, data would quickly

accumulate and hopefully become statistically significant much sooner than

using an environmental chamber approach in an academic setting.

 

In summary, I have shown approaches to MCS which in my opinion are promising

and will help to further define the mechanisms underlying the development of

MCS.

 

 

Correspondence:

 

Gunnar Heuser, MD, PhD, FACP, FACFE, BCFE

NeuroMed and NeuroTox Associates

A Medical Group

28240 W. Agoura Rd., Suite 203

Agoura Hills, California 91301 USA

818-865-1858

Fax 818-865-8814

 

 

References

 

1. The Mastocytosis Society, Inc. 2010 North Grand Avenue, Connersville, IN

47331.

 

2. Bartha L, et al, Multiple chemical sensitivity: A 1999 consensus. Arch

Environ Hlth 1999; 54:147-149.

 

3. Heuser G, Letter to the editor regarding Mast cell disorder to be ruled

out in MCS. Arch Environ Hlth 2000; 55:284-285.

 

4. Heuser G, Wu JC, Subcortical hypermetabolism and cortical hypometabolism

after neurotoxic exposure. Human PET studies. 7th International symposium on

neurobehavioral methods and effects in occupational and environmental health.

Stockholm, Sweden June 20-23, 1999.

 

5. Heuser G, Wu JC, Deep subcortical (incl. limbic) hypermetabolism in

patients with chemical intolerance. Human PET studies. Annals of the NY Academy

of

Sciences. 2001(in press).

 

6. Heuser G, Wojdani A, Heuser S, Diagnostic markers of multiple chemical

sensitivity. In: Multiple Chemical Sensitivities, Addendum to Biologic Markers

in

Immunotoxicology. National Academy Press, Washington, D.C. 1992; 117-138.

 

 

Baseline + 4 hours + 20 hours

 

TA1 # 820 1170 820 pt 1

 

570 760 680 pt 2

 

580 588 660 control

 

 

T3 + # 1460 1880 1280 pt 1

 

1460 1650 1440 pt 2

 

1030 1170 1090 control

 

 

Table 1 shows changes from baseline in two chemically sensitive patients

exposed to perfume. Note lesser or no change in age and sex matched control when

counting TA1 and T3 + cells four and twenty hours after exposure.

 

 

 

pt. 1 pt. 2 control

 

FEV 0.5 -25 +11 +37

 

FEV 1 -11 -5 +5

 

FEV 1/FVC -3 -4 +3

 

FEF 25-75% -33 -14 -5

 

 

Table 2. % changes in some parameters of pulmonary function in two chemically

sensitive patients in comparison with an age and sex matched control after

exposure to perfume.