Veterans and Agent Orange Update 2014 (2016) / Chapter Skim
Currently Skimming:
11 Neurologic Disorders
11 Neurologic Disorders
Pages 743-780
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 743... ...
. Because diagnostic specificity is improbable in both the studies upon which the conclusion of limited or suggestive association with exposure to military herbicides were based and in the documentation for the claims submitted to VA by Vietnam veterans, the committee clarifies that the finding for PD should be interpreted by VA to include all diseases with Parkinson-like symptoms unless those symptoms can be definitively attributed to be secondary to an external agent other than the herbicides sprayed in Vietnam.
|
From page 744... ...
, depression, and anxiety -- and from chronic fatigue syn drome. While the increased risks of these conditions among veterans of all US conflicts are of scientific and public health concern, this committee, like previous Veterans and Agent Orange (VAO)
|
From page 745... ...
Case identification in neurologic disorders is often difficult because there are few disorders for which there are specific diagnostic tests. Many disorders result only in molecular or biochemical effects, so even the most advanced imaging techniques can miss abnormalities.
|
From page 746... ...
Biologic Plausibility Experimental data regarding the biologic plausibility of a connection be tween exposure to the COIs and various neurologic disorders continue to accrue. This section summarizes in a general way some of the information reviewed in the current update and, for completeness, includes pertinent information from prior updates.
|
From page 747... ...
. Neuronal cul tures treated with 2,4-D exhibited decreased neurite extension associated with intracellular changes, including a decrease in microtubules, inhibition of the polymerization of tubulin, disorganization of the Golgi apparatus, and inhibi tion of ganglioside synthesis (Rosso et al., 2000a,b)
|
From page 748... ...
Conclusions from VAO and Previous Updates On the basis of the data available at the time, the committees responsible for VAO, Update 1996, Update 1998, Update 2000, Update 2002, Update 2004, Update 2006, Update 2008, Update 2010, and Update 2012 concluded that there was inadequate or insufficient evidence to determine whether there is an associa tion between exposure to the COIs and neurobehavioral disorders. The data that informed that conclusion were mostly from the Air Force Health Study (AFHS, 1991a,b, 1995, 2000; Barrett et al., 2001, 2003)
|
From page 749... ...
None of the endpoints measured differed in fre quency between the two groups. Of the rice farmers, 63.2 percent reported exposure to herbicides, but exposure specificity for the comparisons was insuf ficient for the results to be regarded as fully informative for VAO purposes.
|
From page 750... ...
More research on the COIs and these endpoints, particularly in the offspring of exposed parents, is warranted given findings in studies that address biologic plausibility. Conclusion On the basis of the evidence reviewed here and in previous VAO reports, the committee concludes that there is inadequate or insufficient evidence to determine whether there is an association between exposure to the COIs and neurobehavioral (cognitive or neuropsychiatric)
|
From page 751... ...
, which are considerably more specific than the outcomes evaluated in previous VAO updates. Parkinson Disease and Parkinsonism PD is a progressive neurodegenerative disorder that affects millions of people worldwide.
|
From page 752... ...
Complex genetics may be found to account for an increasing number of PD cases in coming years, but environmental risk factors clearly are also important. Conclusions from VAO and Previous Updates The committees responsible for VAO, Update 1996, Update 1998, Update 2000, Update 2002, Update 2004, and Update 2006 concluded that there was inadequate or insufficient information to determine whether there is an associa tion between exposure to the COIs and PD.
|
From page 753... ...
. In the Korean Veterans Health Study (Yi et al., 2014b)
|
From page 754... ...
a n OR (95% CI) Neurologic Dysfunction Kang et al., 10 PD deaths 5,313 non- Vietnam veterans -- All COIs 10 PD Vietnam cohort: Diagnosis from death 2014 (2,260 in deployed US information obtained from cases 1.3 (0.3–4.6)
|
From page 755... ...
masked facies, database assessment employing a micrographia, or checklist and record of postural imbalance symptoms, reviewed by a neurologist specializing in movement disorders Firestone Enrolled 526 unrelated Structured face-to-face 2,4-D 8 0.8 (0.3–2.0) ≥ 2 of 4 cardinal signs; et al., 2010 cases controls interviews; demographic must have bradykinesia (updates increased information collected, job or resting tremor, may and expands from 250 descriptions (if held for have cogwheel rigidity, Firestone (in original more than 6 mos)
|
From page 756... ...
Tanner et al., 519 cases; 521 controls Telephone interviewers 2,4-D 16 2.6 (1.0–6.5) Enrolling investigator 2009; US consecutively frequency collected information determined diagnosis eligible matched about exposures before the and type of subjects to cases by reference age; employment Parkinsonism, Unified between July age, sex, and history -- industry, Parkinson Disease 1, 2004, and location location, processes, Rating Scale score, and May 31, materials, and job tasks clinical features 2007 Toxicant exposure collected for some jobs Brighina 833 PD 472 Self-report down to For youngest quartile at diagnosis: PD diagnosed by et al., 2008; sequential unaffected specific herbicides; Pesticides (ever)
|
From page 757... ...
institute in and average duration of products East Texas exposure to herbicides and specific pesticides, among other exposures Hancock 319 cases 296 All comparisons referentPesticide application: 200 1.6 (1.1–2.3) et al., 2008; unaffected to those who never applied Insecticides: 1.8 (1.2–2.8)
|
From page 758... ...
a n OR (95% CI) Neurologic Dysfunction Firestone 250 (156 388 (241 Interview determining Occupational, men only Controlled for age, sex, et al., 2005; men)
|
From page 759... ...
Taylor et al., 140 147 controls Interview -- exposure Logistic analysis adjusted for age, sex, family history, Neurologic exam 1999; referred by recorded as total days for education, smoking, water source, head injury, depression Boston cases lifetime Pesticides: 1.0 (0.9–1.2) Medical Herbicides: 1.1 (0.7–1.7)
|
From page 760... ...
a n OR (95% CI) Neurologic Dysfunction Hertzman 127 245 Interview -- occupation Cases vs voters -- among Neurologic exam et al., 1994; (71 men and (121 with with probable pesticide men Canada 56 women)
|
From page 761... ...
propionic acid or Silvex; AHS, Agricultural Health Study; AO, Agent Orange; CI, confidence interval; COI, chemical of interest; EOI, Exposure Opportunity Index; JEM, job–exposure matrix; HR, hazard ratio; na, not applicable; NCHS, National Center for Health Statistics; OR, odds ratio; PCB, polychlorinated biphenyl; PD, Parkinson disease; RDD, random-digit dialing; VA, US Department of Veterans Affairs; VV, Vietnam veteran. aFor the objective of the VAO review series, only associations with herbicides are of possible relevance; only the phenoxy herbicides, cacodylic acid, and picloram are of specific interest.
|
From page 762... ...
. For the overall herbicide exposure estimates, the medium and high groups
|
From page 763... ...
(2007) found that rat cerebellar granule cells in culture (an in vitro model using cells not involved in PD pathology)
|
From page 764... ...
A general summary of the biologic plausibility of neurologic effects arising from exposure to the COIs is presented at the beginning of this chapter. Synthesis The committee responsible for Update 2014 reviewed two new epidemio logic studies that examined herbicide exposure and PD mortality in Vietnam veterans that did not find an association (Kang HK et al., 2014; Yi et al., 2014b)
|
From page 765... ...
G23.8 Other specified degenerative striatonigral diseases of basal ganglia Parkinsonian syndrome G23.9 Degenerative disease of basal associated with: ganglia, unspecified idiopathic orthostatic hypotension symptomatic orthostatic hypotension Progressive supranuclear ophthalmoplegia Shy-Drager syndrome continued
|
From page 766... ...
The revised coding system has progressed by providing individual codes for specific types of secondary Parkinsonism, which should facilitate VA's processing of claims submitted since the ICD-10 codes became effective on Oc tober 1, 2015. Because the veteran is to be given the benefit of the doubt in the claims process, the current committee does not judge it reasonable to exclude from coverage for this presumptively service-related condition any Vietnam vet erans with arkinsonian symptoms unless VA can definitively establish, on a P
|
From page 767... ...
Summary of Previous Updates ALS was first evaluated as a disease that might be associated with the COIs by the committee for Update 2002. Pesticide or herbicide exposure has been associated with an increased risk of ALS, including a doubling of the risk after long-term occupational exposure to pesticides (Deapen and Henderson, 1986)
|
From page 768... ...
Neurologic Dysfunction Yi et al., 2014a 290 111,436 Korean Vietnam veterans -- + Low (158) vs high (132)
|
From page 769... ...
ALS Society of America 1986; US pesticides NOTE: 2,4-D, 2,4-dichlorophenoxyacetic acid; 2,4,5-T, 2,4,5-trichlorophenoxyacetic acid; AHS, Agricultural Health Study; ALS, amyotrophic lateral sclerosis; AO, Agent Orange; CI, confidence interval; EOI, Exposure Opportunity Index; HR, hazard ratio; nr, not reported. aFor the objective of the VAO review series, only associations with herbicides are of possible relevance; only phenoxy herbicides, cacodylic acid, and picloram are of specific interest.
|
From page 770... ...
. In the study of disease prevalence among the Korean Vietnam veterans, after adjusting for age, rank, smoking, drinking, physical activity, domestic use of herbicides, education, income, and BMI, Yi et al.
|
From page 771... ...
There also are studies that suggest ROS could alter specific signaling cascades and be involved in neurodegeneration. Although they do not specifically concern the COIs, such studies are potentially relevant inasmuch as TCDD and herbicides have been reported to elicit oxidative stress (Celik et al., 2006; Shen et al., 2005)
|
From page 772... ...
Conclusions On the basis of the evidence reviewed here and in previous VAO reports, the committee concludes that the evidence of an association between exposure to the COIs and ALS remains inadequate or insufficient. Alzheimer Disease Alzheimer disease is a progressive, neurodegenerative form of dementia that is characterized by memory loss, confusion, mood changes, social with drawal, and deteriorating judgment.
|
From page 773... ...
. In the study of disease prevalence among the Korean Vietnam veterans, after adjustiing for age, rank, smoking, drinking, physical activity, domestic use of herbicides, education, income, and BMI, Yi et al.
|
From page 774... ...
A general summary of the biologic plausibility of neurologic effects of ex posure to the COIs is presented at the beginning of this chapter. Synthesis The findings in the Korean Vietnam Veterans Study (Yi et al., 2014a,b)
|
From page 775... ...
Summary from VAO and Previous Updates The committee for Update 2010 decided to move health outcomes that are manifested shortly after exposure to the COIs (TCDD in particular) to an ap pendix because they are no longer of interest for Vietnam veterans whose expo sure occurred decades ago.
|
From page 776... ...
Given the underlying risk of neu ropathy inherent in patients who have diabetes, the lack of information regarding the duration of diabetes and the small numbers of subjects render this study dif ficult to evaluate. Update of the Scientific Literature Vietnam-Veteran Studies In the study of disease prevalence among the Korean Vietnam veterans, after adjusting for age, rank, smoking, drinking, physical activity, domestic use of herbicides, education, income, and BMI, Yi et al.
|
From page 777... ...
The findings of the large study of Korean Vietnam veterans were small and non-compelling. Conclusions The committee for Update 2010 concluded that, in addition to evidence supporting an association for transient early-onset peripheral neuropathy, there is limited or suggestive evidence of an association between exposure to the COIs and early-onset peripheral neuropathy that may be persistent.
|
From page 778... ...
Update of the Epidemiologic Literature No epidemiologic studies addressing herbicide exposure and hearing loss have been published since Update 2012. Biologic Plausibility Although no studies of hearing loss in adult animals directly exposed to the COIs were found, Crofton and Rice (1999)
|
From page 779... ...
observed an association only in insecticide applicators, not in herbicide applicators. The O'Toole study evaluated Vietnam veterans, but it used the general population as a comparison group, not veterans from the same era who were not deployed to Vietnam, so it could not distinguish between hearing loss that may be associated with noise-related to military service and hearing loss potentially associated with exposures to toxic chemicals.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.