Health symptom trajectories and neurotoxicant exposures in Gulf War veterans: the Ft. Devens cohort

Background Thirty years ago, Gulf War (GW) veterans returned home with numerous health symptoms that have been associated with neurotoxicant exposures experienced during deployment. The health effects from these exposures have been termed toxic wounds. Most GW exposure-outcome studies utilize group analyses and thus individual fluctuations in symptoms may have been masked. This study investigates health symptom trajectories in the same veterans over 25 years. Methods Veterans were categorized into 5 a priori trajectory groups for each health symptom and Chronic Multisymptom Illness (CMI) clinical case status. Multinomial logistic regression models were used to investigate associations between these trajectories and neurotoxicant exposures. Results Results indicate that more than 21 Pyridostigmine Bromide (PB) pill exposure was associated with consistent reporting of fatigue, pain, and cognitive/mood symptoms as well as the development of six additional symptoms over time. Chemical weapons exposure was associated with both consistent reporting and development of neurological symptoms over time. Reported exposure to tent heater exhaust was associated with later development of gastrointestinal and pulmonary symptoms. Veterans reporting exposure to more than 21 PB pills were more than 8 times as likely to consistently meet the criteria for CMI over time. Conclusion This study highlights the importance of the continued documentation of the health impacts experienced by GW veterans’, their resulting chronic health symptoms, and the importance of exposure-outcome relationships in these veterans now 30 years post-deployment.

Under-recognition of medically unexplained symptom conditions among US Veterans with Gulf War Illness

Objective Conditions defined by persistent “medically unexplained” physical symptoms and syndromes (MUS) are common and disabling. Veterans from the Gulf War (deployed 1990–1991) have notably high prevalence and disability from MUS conditions. Individuals with MUS report that providers do not recognize their MUS conditions. Our goal was to determine if Veterans with MUS receive an ICD-10 diagnosis for a MUS condition or receive disability benefits available to them for these conditions. Methods A chart review was conducted with US Veterans who met case criteria for Gulf War Illness, a complex MUS condition (N = 204, M = 53 years-old, SD = 7). Three coders independently reviewed Veteran’s medical records for MUS condition diagnosis or service-connection along with comorbid mental and physical health conditions. Service-connection refers to US Veterans Affairs disability benefits eligibility for conditions or injuries experienced during or exacerbated by military service. Results Twenty-nine percent had a diagnosis of a MUS condition in their medical record, the most common were irritable colon/irritable bowel syndrome (16%) and fibromyalgia (11%). Slightly more Veterans were service-connected for a MUS condition (38%) as compared to diagnosed. There were high rates of diagnoses and service-connection for mental health (diagnoses 76% and service-connection 74%), musculoskeletal (diagnoses 86%, service-connection 79%), and illness-related conditions (diagnoses 98%, service-connection 49%). Conclusion Given that all participants were Gulf War Veterans who met criteria for a MUS condition, our results suggest that MUS conditions in Gulf War Veterans are under-recognized with regard to clinical diagnosis and service-connected disability. Veterans were more likely to be diagnosed and service-connected for musculoskeletal-related and mental health conditions than MUS conditions. Providers may need education and training to facilitate diagnosis of and service-connection for MUS conditions. We believe that greater acknowledgement and validation of MUS conditions would increase patient engagement with healthcare as well as provider and patient satisfaction with care.

The Department of Veterans Affairs Gulf War Veterans’ Illnesses Biorepository: Supporting Research on Gulf War Veterans’ Illnesses

Aims: To introduce resource supporting research on Gulf War illness (GWI) and related disorders, the Gulf War Veterans’ Illnesses Biorepository (GWVIB). Methods: Gulf War era veterans (GWVs) are recruited nationally and enrolled via telephone and email/postal mail. Enrolled veterans receive annual telephone and mail follow-up to collect health data until their passing. A postmortem neuropathological examination is performed, and fixed and frozen brain and spinal cord samples are banked to support research. Investigators studying GWI and related disorders may request tissue and data from the GWVIB. Results: As of September 2021, 127 GWVs from 39 states were enrolled; 60 met the criteria for GWI, and 14 met the criteria for chronic multisymptom illness (CMI). Enrollees have been followed up to six years. Postmortem tissue recoveries were performed on 14 GWVs. The most commonly found neuropathologies included amyotrophic lateral sclerosis, chronic traumatic encephalopathy, and Lewy body disease. Tissue was of good quality with an average RNA integrity number of 5.8 (SD = 1.0) and ≥4.8 in all of the cases. Discussion: The availability of health data and high-quality CNS tissue from this well-characterized GWV cohort will support research on GWI and related disorders affecting GWVs. Enrollment is ongoing.

Brain–Immune Interactions as the Basis of Gulf War Illness: Clinical Assessment and Deployment Profile of 1990–1991 Gulf War Veterans in the Gulf War Illness Consortium (GWIC) Multisite Case-Control Study

The Boston University-based Gulf War Illness Consortium (GWIC) is a multidisciplinary initiative developed to provide detailed understanding of brain and immune alterations that underlie Gulf War illness (GWI), the persistent multisymptom disorder associated with military service in the 1990–1991 Gulf War. The core GWIC case-control clinical study conducted in-depth brain and immune evaluation of 269 Gulf War veterans (223 GWI cases, 46 controls) at three U.S. sites that included clinical assessments, brain imaging, neuropsychological testing, and analyses of a broad range of immune and immunogenetic parameters. GWI cases were similar to controls on most demographic, military, and deployment characteristics although on average were two years younger, with a higher proportion of enlisted personnel vs. officers. Results of physical evaluation and routine clinical lab tests were largely normal, with few differences between GWI cases and healthy controls. However, veterans with GWI scored significantly worse than controls on standardized assessments of general health, pain, fatigue, and sleep quality and had higher rates of diagnosed conditions that included hypertension, respiratory and sinus conditions, gastrointestinal conditions, and current or lifetime depression and post-traumatic stress disorder. Among multiple deployment experiences/exposures reported by veterans, multivariable logistic regression identified just two significant GWI risk factors: extended use of skin pesticides in theater (adjusted OR = 3.25, p = 0.005) and experiencing mild traumatic brain injury during deployment (OR = 7.39, p = 0.009). Gulf War experiences associated with intense stress or trauma (e.g., participation in ground combat) were not associated with GWI. Data and samples from the GWIC project are now stored in a repository for use by GWI researchers. Future reports will present detailed findings on brain structure and function, immune function, and association of neuroimmune measures with characteristics of GWI and Gulf War service.