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Gulf War Syndrome: Another Side of the Debate

      To the Editor: In the debate over illness in Gulf War veterans, as with most arguments and disagreements, there are at least 2 sides. In his recent Special Article, Sartin
      • Sartin JS
      Gulf War illnesses: causes and controversies.
      presented in detail the side holding that ill Gulf War veterans are suffering only from common symptoms exaggerated by stress and that organic brain injury from environmental causes is implausible. For the past 5 years this view has dominated research and policy positions in Washington.
      In his commentary, however, Sartin
      • Sartin JS
      Gulf War illnesses: causes and controversies.
      omitted important longknown facts that have caused others of us to question this popular view and consider the possibility that 100,000 Gulf War veterans may have suffered brain injury from exposure to environmental chemical toxins, including low-level sarin nerve agent. Representative examples follow.
      According to Sartin,
      • Sartin JS
      Gulf War illnesses: causes and controversies.
      there is no credible evidence of lowlevel nerve gas exposure among US troops during the Gulf War. Czechoslovakian chemical weapons experts, using detection equipment far superior to US equipment, however, detected sarin several times among US troops.
      • US Senate Committee on Banking, Housing and Urban Affairs
      Dual-Use Exports to Iraq and Their Impact on the Health of the Persian Gulf War Veterans.
      • Tucker JB
      Evidence Iraq used chemical weapons during the 1991 Persian Gulf War.
      This report was never challenged.
      • Coalition chemical detections and health of coalition troops in detection area
      Gulflink: Office of the Special Assistant for Gulf War Illnesses.
      Detections occurred around the fourth day of the bombing (January 19-21, 1991) reportedly after US planes destroyed chemical weapons stockpiles in southern Iraq
      • US Senate Committee on Banking, Housing and Urban Affairs
      Dual-Use Exports to Iraq and Their Impact on the Health of the Persian Gulf War Veterans.
      • Tucker JB
      Evidence Iraq used chemical weapons during the 1991 Persian Gulf War.
      Our epidemiological study demonstrated a high relative risk (4.6) for the most severe brain injury in troops whose paths converged in a nearby area only on those days.
      • Haley RW
      • Kurt TL
      Self-reported exposure to neurotoxic chemical combinations in the Gulf War: a cross-sectional cpidemiologic study.
      According to Sartin,
      • Sartin JS
      Gulf War illnesses: causes and controversies.
      there is no evidence of permanent brain injury from sarin at doses below the LD50. Classic studies have demonstrated, however, that low, subsymptomatic doses of sarin administered subcutaneously or by inhalation daily over 2 weeks produce permanent neurologic damage in 2 species.
      • Husain K
      • Vijayaraghavan R
      • Pant SC
      • Raza SK
      • Pandey KS
      Delayed neurotoxic effect of sarin in mice after repeated inhalation exposure.
      • Husain K
      • Pant SC
      • Raw SK
      • Singh R
      • Das Gupta S
      A comparative study of delayed neuroloxicity in hens following repeated administration of organophosphorus compounds.
      According to Sartin,
      • Sartin JS
      Gulf War illnesses: causes and controversies.
      sarin sarin exposure in the terrorist attack in the Tokyo subway, pesticide exposures in agricultural workers, and US Army human exposures to sarin indicate no significant effects of subclinical doses. Tokyo physicians, however, reported chronic vestibular damage, similar to our findings in veterans,
      • Haley RW
      • Kurt TL
      Self-reported exposure to neurotoxic chemical combinations in the Gulf War: a cross-sectional cpidemiologic study.
      • Roland PS
      • Haley RW
      • Ycllin W
      • Owens K
      • Shoup AG
      Vestibular dysfunction in Gulf War syndrome.
      in proportion to the dose of sarin sustained.
      • Murata K
      • Araki S
      • Yokoyama K
      • et al.
      Asymptomatic sequelae to acute sarin poisoning in the central and autonomie nervous system 6 months after the Tokyo subway attack.
      • Yokoyama K
      • Araki S
      • Murata K
      • et al.
      A preliminary study of delayed vcstibulo-cerebellar effects of Tokyo subway sarin poisoning in relation to gender difference: frequency analysis of postural sway.
      • Yokoyama K
      • Araki S
      • Murata K
      • et al.
      Chronic ncurobchavioral and central and autonomie nervous system effects of Tokyo subway sarin poisoning.
      There is a substantial body of literature documenting permanent central nervous system damage in agricultural workers and others exposed to some organophosphate pesticides, often occurring in clusters and epidemics.
      • Ecobichon DJ
      Organophosphorus ester insecticides.
      Electroencephalographic studies demonstrated evidence of permanent brain injury in symptomatic chemical weapons plant workers exposed accidentally to lowlevel sarin at the Aberdeen Proving Ground.
      • Duffy FH
      • Burchfiel JL
      • Bartels PH
      • Gaon M
      • Sim VM
      Long-term effects of an organophosphatc upon the human electroencephalogram.
      The investigators reproduced the findings by exposing primates to low-level sarin experimentally.
      • Burchfiel JL
      • Duffy FH
      • Van Sim M
      Persistent effects of sarin and dicldrin upon the primate electroencephalogram.
      According to Sartin,
      • Sartin JS
      Gulf War illnesses: causes and controversies.
      our studies demonstrating brain damage in ill Gulf War veterans presented no objective measurements. On the contrary, we published audiovestibular and evoked potential measurements performed by blinded investigators that demonstrated evidence of brainstem and/or basal ganglia dysfunction in ill veterans vs controls
      • Roland PS
      • Haley RW
      • Ycllin W
      • Owens K
      • Shoup AG
      Vestibular dysfunction in Gulf War syndrome.
      • Haley RW
      • Horn J
      • Roland PS
      • et al.
      Evaluation of neurologic function in Gulf War veterans: a blinded case-control study.
      .; a strong association with a genetic polymorphism linking Gulf War syndrome with sarin exposure
      • Haley RW
      • Billeeke S
      • La Du BN
      Association of low PON] type Q (type A) arylesterasc activity with neurologic symptom complexes in Gulf War veterans.
      ; and magnetic resonance spectroscopy scans demonstrating marked reductions in functioning neuronal mass in basal ganglia and brainstem of ill veterans compared with controls.
      • Haley RW
      • Marshall WW
      • McDonald GG
      • Daughcrty MA
      • Petty F
      • Fleckcnstein JI
      Brain abnormalities in Gulf War syndrome: evaluation by 'H MR spectroscopy.
      • Haley RW
      • Fleckcnstcin JL
      • Marshall WW
      • McDonald GG
      • Kramer GL
      • Petty F
      Effect of basal ganglia injury on central dopamine activity in Gulf War syndrome: correlation of proton magnetic resonance spectroscopy and plasma homovanillic acid levels.
      A decade after the war, tens of thousands of Gulf War veterans may be suffering a characteristic set of neurologic symptoms,
      • Haley RW
      • Kurt TM
      • Horn J
      Is there a Gulf War syndrome? searching for syndromes by factor analysis of symptoms [published correction appears in JAMA. 1997;278:388].
      and the rate of VA-acknowledged disability is 2 to 3 times higher than after any prior war.
      • Thompson J
      Statement to House Committee on Veterans' Affairs, Subcommittee on Benefits.
      As physicians trying to understand this problem and serve these veterans, we must resist the human tendency to censor the facts to conform with strong popular viewpoints.

      REFERENCES

        • Sartin JS
        Gulf War illnesses: causes and controversies.
        Mayo Clin Proc. 2000; 75: 811-819
        • US Senate Committee on Banking, Housing and Urban Affairs
        Dual-Use Exports to Iraq and Their Impact on the Health of the Persian Gulf War Veterans.
        (Accessed September 28, 2000.)
        • Tucker JB
        Evidence Iraq used chemical weapons during the 1991 Persian Gulf War.
        Nonprotiferation Rev. Spring-Summer 1997; 4 (Accessed September 28, 2000.): 114-122
        • Coalition chemical detections and health of coalition troops in detection area
        Gulflink: Office of the Special Assistant for Gulf War Illnesses.
        (Accessed August 9, 2000.)
        • Haley RW
        • Kurt TL
        Self-reported exposure to neurotoxic chemical combinations in the Gulf War: a cross-sectional cpidemiologic study.
        JAMA. 1997; 277: 231-237
        • Husain K
        • Vijayaraghavan R
        • Pant SC
        • Raza SK
        • Pandey KS
        Delayed neurotoxic effect of sarin in mice after repeated inhalation exposure.
        J Appl Toxicol. 1993; 13: 143-145
        • Husain K
        • Pant SC
        • Raw SK
        • Singh R
        • Das Gupta S
        A comparative study of delayed neuroloxicity in hens following repeated administration of organophosphorus compounds.
        Indian J Physiol Pharmacol. 1995; 39: 47-50
        • Roland PS
        • Haley RW
        • Ycllin W
        • Owens K
        • Shoup AG
        Vestibular dysfunction in Gulf War syndrome.
        Otolaryngol Head Neck Surg. 2000; 122: 319-329
        • Murata K
        • Araki S
        • Yokoyama K
        • et al.
        Asymptomatic sequelae to acute sarin poisoning in the central and autonomie nervous system 6 months after the Tokyo subway attack.
        J Neurol. 1997; 244: 601-606
        • Yokoyama K
        • Araki S
        • Murata K
        • et al.
        A preliminary study of delayed vcstibulo-cerebellar effects of Tokyo subway sarin poisoning in relation to gender difference: frequency analysis of postural sway.
        J Occup Environ Med. 1998; 40: 17-21
        • Yokoyama K
        • Araki S
        • Murata K
        • et al.
        Chronic ncurobchavioral and central and autonomie nervous system effects of Tokyo subway sarin poisoning.
        J Physiol Paris. 1998; 92: 317-323
        • Ecobichon DJ
        Organophosphorus ester insecticides.
        in: Ecobinchon DJ Joy RM Pesticides and Neurological Diseases. CRC Press, Boca Raton, Fla1994: 171-250
        • Duffy FH
        • Burchfiel JL
        • Bartels PH
        • Gaon M
        • Sim VM
        Long-term effects of an organophosphatc upon the human electroencephalogram.
        Toxicol Appl Pharmacol. 1979; 47: 161-176
        • Burchfiel JL
        • Duffy FH
        • Van Sim M
        Persistent effects of sarin and dicldrin upon the primate electroencephalogram.
        Toxicol Appl Pharmacol. 1976; 35: 365-379
        • Haley RW
        • Horn J
        • Roland PS
        • et al.
        Evaluation of neurologic function in Gulf War veterans: a blinded case-control study.
        JAMA. 1997; 277: 223-230
        • Haley RW
        • Billeeke S
        • La Du BN
        Association of low PON] type Q (type A) arylesterasc activity with neurologic symptom complexes in Gulf War veterans.
        Toxicol Appl Pharmacol. 1999; 157: 227-233
        • Haley RW
        • Marshall WW
        • McDonald GG
        • Daughcrty MA
        • Petty F
        • Fleckcnstein JI
        Brain abnormalities in Gulf War syndrome: evaluation by 'H MR spectroscopy.
        Radiology. 2000; 215: 807-817
        • Haley RW
        • Fleckcnstcin JL
        • Marshall WW
        • McDonald GG
        • Kramer GL
        • Petty F
        Effect of basal ganglia injury on central dopamine activity in Gulf War syndrome: correlation of proton magnetic resonance spectroscopy and plasma homovanillic acid levels.
        Arch Neural. 2000; 57: 1280-1285
        • Haley RW
        • Kurt TM
        • Horn J
        Is there a Gulf War syndrome? searching for syndromes by factor analysis of symptoms [published correction appears in JAMA. 1997;278:388].
        JAMA. 1997; 277: 2I5-222
        • Thompson J
        Statement to House Committee on Veterans' Affairs, Subcommittee on Benefits.
        (Accessed August 9. 2000)

      Linked Article

      • Gulf War Syndrome: Another Side of the Debate: In Response
        Mayo Clinic ProceedingsVol. 75Issue 11
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          Dr Haley's letter in reaction to my recent article notes my agreement with the majority of Gulf War illnesses investigators and spokespersons, including those affiliated with the Department of Defense. It should be noted that I am no longer in the military and have not collaborated with scientists in the Department of Defense, nor do I have a special interest in promoting their conclusions. Having seen a large number of patients with Gulf War illnesses, I sought to provide a broad overview of the research on Gulf War illnesses and to put the controversies in perspective.
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