Multiple Chemical Sensitivity ... or MUSES Syndrome ?

1. Multiple Chemical Sensitivity... or MUSES Syndrome ? Presented to the Environmental Law Centre’sInternational MCS Conference 8 April 2002, Conway Hall, London(c) 2002 by Albert Donnay, MHS MCS Referral & Resources, Incwww.mcsrr.orgadonnay@jhu.edu

2. What is Multiple Chemical Sensitivity? • 1999 Consensus Definition (Arch Env Health 1999;54:147-9) [1] MCS is a chronic condition [2] marked by multiple symptoms in multiple organs [3] that recur reproducibly [4] in response to low levels of exposure [5] to multiple unrelated chemicals and [6] improve or resolve when incitants are removed. • Best of 7 MCS Definitions at identifying MCS cases(McKeown-Eyssen et al, Arch Env Health 2001;56:406-12)

3. CARDIOVASCULAR 9 DIGESTIVE 18 EARS // HEARING 7 EYES // VISION 12 GENITO-URINARY 10 HEAD 6 MOUTH // TASTE 14 MUSCULOSKEL. 14 NECK 3 NERVOUS SYSTEM 43 NOSE // SMELL 10 SYSTEMIC // OTHER 17 VASCULAR 5 REPRODUCTIVE 17 RESPIRATORY 6 SKIN // TOUCH 7 THROAT 5 TOTAL # SYMPTOMS = 203 How Many MCS Symptoms Have Been Reported ? List compiled by JHU Multi-Center Study of MCS Immunology

4. What Objective Findings Are Reported in MCS ? • Musculoskeletal Abnormalities • Neurocognitive Deficiencies • Nose & Smell Abnormalitites • Porphyrin Enzyme Abnorm. • Respiratory Impairment • Sensory Nerve Impairment • Skin Tone Abnormalities • Vestibular Impairment • Vitamin Deficiencies • Xenobiotics in Fat, Blood, Urine and HairRefs online at www.mcsrr.org • Abnormal Blood & Plasma • Impaired Circulation • Impaired Heart Function • Impaired Detox Pathways • Ear & Hearing Abnormalities • Endocrine Deficiencies • Eye & Vision Abnormalities • Gastrointestinal Impairment • Immune System Activation • Increased Mast Cells • Mineral Deficiencies

5. Who is Funding This MCS Research? • Most MCS-related papers do not acknowledge any funding ! • But 10 US federal agencies fund over $25M per year: ATSDR, CDC, DOD, DOE, DVA, EPA, NIDCD, NIEHS, NIH & NIOSH • US Dept of Defense also funds MCS studies of UK veterans • State governments in California, Maryland, Missouri, New Jersey, New Mexico & Washington have funded MCS studies • Both patient support groups (eg. CIIN) and chemical industry front groups (eg. ESRI) have funded MCS conferences and pilot studies, which usually have a strong bias.

6. What View Predominates: Physical or Psychiatric? Overlaps:Only 11% of First Authors and 30% of Publishers have ever supported more than one view

7. On What Do All Agree? Prevalence is Very High ! • 5 US studies find 28% - 37% of adults say they are “especially sensitive” to common chemical exposures • 4 US studies find 15% - 17% say they’re “unusually sensitive” • 6.3% in CA and 1.9% in NM say they have been diagnosedby a medical professional with MCS or “environmental illness” • US, Canadian and UK studies of Gulf War veterans all find an increased prevalence of (still undiagnosed) MCS with a relative risk of 2 to 4 compared with undeployed era controls • So whatever cause, must be very common & moreso in war.

8. But is MCS Only a Disorder of Chemical Sensitivity? • Not just ODOURS: LIGHT & SOUND HYPERSENSITIVITY are very strongly associated with MCS: p < 0.00001 (Miller, Tox Ind Health, 1999;15:370-85) • When asked, MCS patients also report hypersensitivity to: TASTES // FOODS TOUCH // PRESSURE // PAIN HOT or COLD WEATHER ELECTROMAGNETIC FIELDS HEAVY METALS MENTAL or PHYSICAL EFFORT STRESS OF ANY KIND In an audience poll conducted at this point, approx. 75 people reported having all these sensory sensitivities since ill. Only one (an American) reported having just chemical sensitivity, aka pure MCS.

9. Might MCS Be Something Else as Critics Claim? • Not New or Unique in English or French Medical Literature • At Least 133 Similar Syndromes “Discovered” Before & Since • Few acknowledge any relation to any others, past or current • Few propose any specific cause, etiology or biomarkers • Hence most never widely adopted or eventually abandoned • But some are still in use and many MCS case are still being diagnosed by one or more of them depending on the doctor • History reveals both consistency of underlying syndrome and great inconsistency of evolving medical awareness, proving doctors rarely ever discover anything new, just things they forgot, were never taught or did not bother to look up first !

10. First Described in 1733 by Dr. George Cheyne as the English Malady (EM!), aka The Vapours • “To enumerate all the almost infinite Symptoms, Degrees and Kinds of Vapours is impossible, and perhaps very little to the Purpose. • In general … the symptoms are many, various, changeable, shifting from one Place to another, and imitating the Symptoms of almost every other Distemper described.” • “Those who suffer … are all of weak Nerves, have a great degree of sensibility; are quick Thinkers, feel Pleasure or Pain the most readily, and are of most lively imagination.” • “Not withstanding all this, the Disease is as much a bodily Distemper as the Small-Pox or a Fever.” • Worst in winter & cities. Blamed on bad air, bad diet & bad habits.

11. Some Symptoms of E.M. Cited by Dr Cheyne “Sometimes there is an Inflation, and an actual visible Swelling, to a very considerable Bigness, in the Stomach to be seen, especially in the Sex [women]; a Coldness or Chilliness upon the Extremities, and sometimes Flushing and Burning in the Hands and Feet, Cold Damp Sweats, Faintings, and Sickness … Head-aches either behind or over the Eyes, … Flies and Atoms dancing before the Eyes, a Noise like the dying Sounds of Bells, or a Fall of Water, in the Ears; Yawning, and Stretching, and sometimes a Drowsiness or Lethargy, at other times Watching and Restlessness, and several other Symptoms, which it is impossible to enumerate. Some have but a few of these Symptoms, and some all of them, and a great many more…”

12. 1733 The English Malady aka The Vapours 1769 Dysesthesia 1837 Neuropathy of Nervousness 1849 Nervosisme 1861 Ménière's Disease 1869 Neurasthenia >1K* 1892 Hyperaesthesia 1894 Autointoxication 1921 Chronic CO Poisoning 1930 Heat, Cold and & Effort Sensitiveness 36 Focus on Allergy, Sensitivity, Neurology or Toxins 1930 Allergic Toxemia 1945 Allergic Fatigue and Weakness 1945 Hyperventilation Asthma 1952 Allergy of Nervous System 1954 Cerebral Allergy 1956 Specific Adaptation Syn. 1957 Familial Dysautonomia >9K 1965 Minimal Brain Dysfunction 1965 Delayed Hypersensitivity Reaction >4K 1973 Sensory Integrative Dysfunction * 1K = 1000 references on PubMed

13. 1978 Chemical Hypersusceptibility 1979 Perinatal Hypoxic- Ischemic Cerebral Syn. 1982 Total Allergy Syndrome 1983 Sick Building Syndrome 1985 20th Century Syndrome 1985 Allergic Irritability Syn. 1985 Environmental Hypersensitivities 1986 Hypersensitivity Syndrome 1987 Darkroom Disease 1987 Multiple Chemical Sensitivity <700 Allergy, Sensitivity, Neurology or Toxinscontinued … 1990 Chronic Habitual Hyperventilation Syn. 1994 Gulf War Syndrome 1996 Multi-Organ Dysesthesia 1998 Toxicant Induced Loss of Tolerance 1999 Eco-Syndrome 1999 Multi-Sensory Sensitivity, aka MUSES Syndrome

14. 1875 Spinal Neurasthenia 1881 American Nervousness 1886 Sexual Neurasthenia 1887 Gastric Neurasthenia 1889 Neurasthenia Praecox (aka Male N.) 1890 Psychosomatic Neurasthenia 1891 Female Neurasthenia 1893 Syphilitic Neurasthenia 1895 Senile Neurasthenia 1897 Traumatic Neurasthenia 1898 Encephalasthenia 1903 Disease of the Century 1906 Tropical Neurasthenia 1907 Endocrine Neurasthenia 1907 Ocular Neurasthenia 1908 Digestive Neurasthenia 1909 Battleship Neurasthenia 1968 Pseudoneurasthenic Syndrome 1976 Organic Neurasthenia 1976 Neurasthenic Musculoskeletal Pain Syndrome 30 Focus on Variations of 1869 Neurasthenia:

15. 1980 Neurasthenic Neurosis 1988 Neurasthenic Fatigue Types of Unknown Origin & Date Cited by Secondary Sources Angiopathic Neurasthenia Cardiac Neurasthenia Cardiovascular Neurasthenia Insania Neurasthenia Neurasthenia Chemicorum Neurasthenia Gravis Post-viral Neurasthenia Pulsating Neurasthenia Variations of Neurastheniacontinued …

16. 1765 Nervous, Hypochondriac or Hysteric 1766 Hypochondriasis, aka Hyp or Hypo 1859 Briquet’s Syndrome 1871 Hebephrenia 1895 Anxiety Neurosis >28K 1904 Phrenasthenia 1906 Psychasthenia 1912 Autism >6K 1914 Shell Shock Syndrome 1916 Battle Fatigue Syndrome 1918 War Neurosis 1930 Generalized Anxiety>1.5K 42 Focus on Psychiatry or Behaviour 1938 Suburban Neurosis 1944 Asperger’s Syndrome 1947 Old Sergeant Syndrome 1951 Munchausen’s Syn >1K 1957 Psychogenic Dyspnea and Hyperventilation 1957 Traumatic Neurosis 1965 Asthenic Neurosis 1965 Psychogenic Pain Syn 1966 Psychovegetative Syn 1966 Accident neurosis 1966 Hyperactive Child Syn 1967 Post Accident Anxiety Syn 1968 Chronic Factitious Illness

17. 1968 Pseudo Combat Fatigue 1968 Hyperkinetic Behavior Syn 1973 Ecologic Mental Illness 1973 Psychalgia 1974 Epidemic or Mass Hysteria 1977 Pinocchio Syndrome 1978 Mass Psychogenic Illness 1978 Psychic Possession 1980 Post Traumatic Stress Disorder >6.5K (count incl. Traumatic Neurosis) 1981 Attention Deficit Disorder, aka ADD 1981 Pervasive Developmental Disorder >7K Psychiatry or Behaviour continued … 1981 Somatization Dis. >7K 1988 Attention Deficit Hyperactivity Disorder, aka ADHD, >6K (count includes ADD & HCS) 1995 Environmental Somatization Syndrome 1996 Iatrogenic Hypochondriasis 1996 Idiopathic Environmental Intolerances (not WHO) 1999 Functional Somatic Syndromes

18. 1857 Remittent Fever, aka Crimea Fever 1866 Railway Spine 1871 Irritable Heart, aka DaCosta’s Syndrome 1887 Undulating Fever, aka Malta Fever aka Mediterranean Fever 1904 Fibrositis 1934 Chronic Brucellosis 1936 Morbid Industrial Fatigue 1938 Neurocirculatory Asthenia, aka Effort Syndrome 1941 Chronic Fatigue 1950 Epidemic Neuromyastheniaaka Icelandic Disease, aka Akureyri Fever 1956 Encephalomyelitis simulating Poliomyelitis, aka Royal Free Hospital 1956 Benign ME, aka Myalgic Encephalomyelitis <100 1957 Epidemic Postinfectious Neuromyasthenia 1958 Irritable Colon Syn 1959 Irritable Bowel Syn >3.5K 28 Focus on Infection, Trauma, Fatigue or Pain

19. And Not Just Described By Doctors -- First Reported in USA by Edgar Allan Poe • 1832: 1st Report of Symptoms in Loss of Breath • 1838: Most Detailed Symptoms in Fall of House of Usher • 1839: 1st Report of Facial Sign in The Man Who Was Used Up • 1840: 1st Report of Cause in Philosophy of Furniture • 1843: 1st Report of Medical Debate in The Tell Tale Heart“Now have I not told you that what you mistake for madnessis but overacuteness of the senses?” • 1844: 1st Report of Successful Therapy in Premature Burial • 1849: Dies as he predicted of “Congestion of the Brain”

20. But Only Charles Baudelaire Recognized Gas Lighting as the Cause of Poe’s Symptoms • "All the documents I have read led me to the conviction that for Poe the United States was nothing more than a vast prison which he traversed with the feverish agitation of a being made to breathe a sweeter air --nothing more than a great gas lighted nightmare— and that his inner, spiritual life, as a poet or even as a drunkard, was nothing but a perpetual effort to escape the influence of this unfriendly atmosphere." • Gas made from coal contained 5 % - 50 % carbon monoxide (CO) • CO exposure limits today= 0.0009 % outdoors, 0.005% occupational

21. “Do you know why I so patiently translated Poe? It was because he was like me.” REVERSE IMAGE TRUE IMAGE EDGAR ALLAN POE CHARLES BAUDELAIRE

22. “And there was perceptible about them, ever and anon, just that amount of interesting obliquity…” EA Poe, 1839

23. Many Great English Writers Also Apparently Poisoned by Carbon Monoxide George Bernard Shaw Oscar Wilde

24. Of Course, Not Just Men and Not Just Then Jane Austen J.K. Rowling

25. Tell Tale Face Noted in “Certain Nervous Disorders” Even Before Introduction of Gas Lighting “Her left eyelid remained permanently half closed and the right angle of her mouth was considerably drawn aside.” Edward Percival, 1813

26. England’s Most Famous Unrecognized Case ? King George III1738 – 1820 Presumed now to have inherited porphyria: gas poisoning was never considered since his illness began decades before gas lighting.

27. Most Likely Cause Prior to Gas LightingCoal bed warmer on display in bedroom of his grandmother Queen Caroline, Hampton Court

28. Fibromyalgia Syndrome 2 (both note “not CO”) Chronic Fatigue Syndrome 2 (1 notes “from CO” the other “not CO”) Generalized Anxiety 1 (notes “not CO”) MCS / MUSES Syndrome 1 (notes “from CO”) Post Traumatic Stress Disorder 2 (both note “not CO”) Somatization Disorder 3 (all 3 note “not CO”)Even most MCS patients fail to recognize the connection, perhaps because CO is odourless, tasteless and invisible. CO Role in “MCS etc” Not Yet Widely Recognized: Excluding Literature on Chronic CO Poisoning, CO is mentioned in only 11 of 90,000 other articles

29. First & Only Paper Proposing Connections Between MCS, CO and Poe Donnay, A. International Journal of Toxicology1999;18(6):383-392 “On the recognition of multiple chemical sensitivity in medical literature and government policy.”

30. Anemia Angina Anosmia (loss of smell) Asthma Birth Defects Blindness Deafness Depression Diabetes Hallucinations of all kinds Heart Disease Mental Retardation Parkinson’s Psychoses But CO is Well Known as “The Great Imitator” and Already Well Documented to Cause or Worsen:

31. Why So Many Syndromes? CO is Both Ubiquitous Neurotoxin & Ubiquitous Neurotransmitter • CO is #1 Cause of Unintentional Toxic Deaths in USA • CO is #1 Cause of Unintentional Toxic Poisonings • CO is #1 Air Pollutant: more tons/year than any other, primarily from industry, vehicles, fires, combustion appliances • CO is also made systemically by all mammals from heme breakdown by Heme Oxygenase, the Universal Stress Enzyme. • HO-1 is greatly induced by exposure to any type of stress : heat, bright light, noise, odors, drugs, alcohol and other chemicals, trauma, infection, electro magnetic fields, etc. • CO is not just bound to Hb but bioactive in over 90 pathways

32. Allergy Altitude Sickness Alzheimer’s Anemia Asthma Bronchiectasis Cystic Fibrosis Diabetes Heart Attack Heat Stress / Stroke Methylene Chloride Poisoning Parkinson’s Pre-Menstrual Syndrome Upper Respiratory Tract Infections Increased endogenous production of CO from heme breakdown is documented in:

33. All CO-Related Disorders Share Biomarker: Elevated Level of CO in End-Tidal Breath • Normal bCO (maximum after holding breath 20 to 25 seconds) Healthy Relaxed Non-Smokers = 0-2 ppm • Mildly Elevated bCOBorderline Abnormal for Non-Smokers = 3-4 ppm • Moderately Elevated bCO Smokers and People with CO Disorders = 5-24 ppm • Highly Elevated bCO Recently Smoked or CO Poisoned = 25-999+ppm All healthy adults have approx. noon peak and midnight trough Higher after suppl. oxygen & if standing vs. sitting vs. supine.

34. How CO Causes MUSES Syndrome • CO controls sensitization and habituation to stressors of all kinds • Chronic repeated exposures to any stressor induces habituation, so that higher doses are tolerated with less or no sensory awareness. • Isolated acute exposures (and de-habituation) induce sensitization, so that lower doses are less tolerated with more sensory awareness. • While exogenous stressors (heat, drugs, alcohol) may be avoided, endogenous CO produced by HO in response to ANY stressor cannot. • So if/once sensitized to CO via exogenous poisoning or dehabituation, increased sensory awareness may be provoked by ANY stressor • Result is multi-sensory sensitivity to odours, lights, sounds, foods, etc aka MUSES Syndrome (aka MCS in adults or autism in children).

35. Curing MUSES Syndrome: The Treatments Proposed by Cheyne and Poe are Still Best • Dr. George Cheyne in The English Malady, 1733: “Seldom any lasting or solid cure is perform’d … till they have sucked in and incorporated the sweet balmy clear Air of the Country. … Diet will do infinitely more than Exercise and have more lasting Effects, but both should be joined. … Certainly the best of all is where Amusement or Entertainment of the Mind is joined with Bodily Labour and Constant Change of Air.” • Edgar Allan Poe in The Premature Burial, 1844: “I took vigorous exercise. I breathed the free air of Heaven. I thought upon other subjects than Death. I discarded my medical books.”

36. Where to Look for Evidence of CO Poisoning Today • Test CO in end tidal breath after holding breath for 20 seconds (healthy relaxed non-smoker should be 0 to 2 ppm). • Monitor indoor CO levels with a digital detector near combustion appliances, especially unvented ones like gas ovens and gas logs. • Monitor CO levels in homes with attached garages after vehicles are started and driven out. • Monitor CO levels in motor vehicles while idling and driving. • Look for the asymetrically drooping eye and mouth that mark the Tell Tale Face of CO Poisoning and ask about any multi-sensory sensitivity to lights, odors, noises, tastes, touch and heat or cold.