Role of Deployment History on the Association Between Epilepsy and Traumatic Brain Injury in Post-9/11 Era US Veterans.

BACKGROUND AND OBJECTIVES: Traumatic brain injury (TBI) is a well-established epilepsy risk factor and is common among service members. Deployment-related TBI, where combat/blast may be more common, may have different outcomes than nondeployment-related TBI. This work examined associations of all TBI exposures (not just combat), and epilepsy, while adjusting for comorbidities associated with epilepsy, among veterans by deployment status. METHODS: The cohort included post-9/11 veterans with ≥2 years of care in both Veterans Health Administration and Defense Health Agency systems. We identified epilepsy using ICD-9/10-CM codes, antiseizure medication, and service-connected disability for epilepsy. We conducted a logistic regression model with interaction terms for conditions by deployment history that adjusted for demographics and military characteristics. RESULTS: The cohort (n = 938,890) included post-9/11 veterans of whom 27,436 (2.92%) had epilepsy. Most veterans had a history of deployment (70.64%), referred to as "deployed." Epilepsy was more common among veterans who were never deployed ("nondeployed") (3.85% vs 2.54%). Deployed veterans were more likely to have had TBI, compared with the nondeployed veterans (33.94% vs 14.24%), but nondeployed veterans with moderate/severe TBI had higher odds of epilepsy compared with deployed veterans (adjusted odds ratio [aOR] 2.92, 95% CI 2.68-3.17 vs aOR 2.01, 95% CI 1.91-2.11). Penetrating TBI had higher odds of epilepsy among the deployed veterans (aOR 5.33, 95% CI 4.89-5.81), whereas the odds of epilepsy for mild TBI did not significantly differ by deployment status. Although most neurologic conditions were more prevalent among the nondeployed veterans, they were often associated with higher odds of epilepsy in the deployed veterans. DISCUSSION: Deployment history had a significant differential impact on epilepsy predictors. As expected, penetrating TBI had a greater epilepsy impact among deployed veterans perhaps due to combat/blast. Some epilepsy predictors (moderate/severe TBI, multiple sclerosis, and Parkinson disease) had a stronger association in the nondeployed veterans suggesting a potential healthy warrior effect in which such conditions preclude deployment. Other neurologic conditions (e.g., brain tumor, Alzheimer disease/frontotemporal dementia) had a greater epilepsy impact in the deployed veterans. This may be attributable to deployment-related exposures (combat injury, occupational exposures). A better understanding of deployment effects is critical to provide targeted epilepsy prevention in veterans and military service members.

Comorbidity and polypharmacy impact neurobehavioral symptoms and symptom validity failure among post-9/11 veterans with mild traumatic brain injury.

Objective: The study aimed to examine the association between post-concussive comorbidity burdens [post-traumatic stress disorder (PTSD), depression, and/or headache] and central nervous system (CNS) polypharmacy (five or more concurrent medications) with reported neurobehavioral symptoms and symptom validity screening among post-9/11 veterans with a history of mild traumatic brain injury (mTBI). Setting: Administrative medical record data from the Department of Veterans Affairs (VA) were used in the study. Participants: Post-9/11 veterans with mTBI and at least 2 years of VA care between 2001 and 2019 who had completed the comprehensive traumatic brain injury evaluation (CTBIE) were included in the study. Design: Retrospective cross-sectional design was used in the study. Main measures: Neurobehavioral Symptom Inventory (NSI), International Classification of Diseases, Ninth Revision, and Clinical Modification diagnosis codes were included in the study. Results: Of the 92,495 veterans with a history of TBI, 90% had diagnoses of at least one identified comorbidity (PTSD, depression, and/or headache) and 28% had evidence of CNS polypharmacy. Neurobehavioral symptom reporting and symptom validity failure was associated with comorbidity burden and polypharmacy after adjusting for sociodemographic characteristics. Veterans with concurrent diagnoses of PTSD, depression, and headache were more than six times more likely [Adjusted odds ratio = 6.55 (99% CI: 5.41, 7.92)]. to fail the embedded symptom validity measure (Validity-10) in the NSI. Conclusion: TBI-related multimorbidity and CNS polypharmacy had the strongest association with neurobehavioral symptom distress, even after accounting for injury and sociodemographic characteristics. Given the regular use of the NSI in clinical and research settings, these findings emphasize the need for comprehensive neuropsychological evaluation for individuals who screen positively for potential symptom overreporting, the importance of multidisciplinary rehabilitation to restore functioning following mTBI, and the conscientious utilization of symptom validity measures in research efforts.

Generalized paroxysmal fast activity and tonic seizures in older adults.

Generalized paroxysmal fast activity is an uncommon ictal EEG pattern usually associated with tonic seizures. Patients with generalized paroxysmal fast activity typically have multiple seizure types beginning in childhood and are refractory to antiepileptic drug therapy. We describe 3 hospitalized adult patients (age, older than 55 years) with new-onset tonic movements, noted during an acute illness, associated with generalized paroxysmal fast activity on EEG. These seizures were characterized by subtle stiffening of the arms, trunk, and face for up to 3 seconds. All patients had multiple medical problems and polypharmacy. None had a history of static encephalopathy, other epileptiform abnormalities on EEG, other seizure types, or significant neuroimaging abnormalities. In contrast to previously described reports in children, all three adults responded to antiepileptic drug monotherapy. EEG played a critical role in differentiating tonic seizures from nonepileptic movements in these three cases.

Common data elements in epilepsy research: development and implementation of the NINDS epilepsy CDE project.

The Common Data Element (CDE) Project was initiated in 2006 by the National Institute of Neurological Disorders and Stroke (NINDS) to develop standards for performing funded neuroscience-related clinical research. CDEs are intended to standardize aspects of data collection; decrease study start-up time; and provide more complete, comprehensive, and equivalent data across studies within a particular disease area. Therefore, CDEs will simplify data sharing and data aggregation across NINDS-funded clinical research, and where appropriate, facilitate the development of evidenced-based guidelines and recommendations. Epilepsy-specific CDEs were established in nine content areas: (1) Antiepileptic Drugs (AEDs) and Other Antiepileptic Therapies (AETs), (2) Comorbidities, (3) Electrophysiology, (4) Imaging, (5) Neurological Exam, (6) Neuropsychology, (7) Quality of Life, (8) Seizures and Syndromes, and (9) Surgery and Pathology. CDEs were developed as a dynamic resource that will accommodate recommendations based on investigator use, new technologies, and research findings documenting emerging critical disease characteristics. The epilepsy-specific CDE initiative can be viewed as part of the larger international movement toward "harmonization" of clinical disease characterization and outcome assessment designed to promote communication and research efforts in epilepsy. It will also provide valuable guidance for CDE improvement during further development, refinement, and implementation. This article describes the NINDS CDE Initiative, the process used in developing Epilepsy CDEs, and the benefits of CDEs for the clinical investigator and NINDS.

Are psychiatric disorders independent risk factors for new-onset epilepsy in older individuals?

This retrospective study examined whether psychiatric conditions are directly related to epilepsy or, rather, are associated with underlying central nervous system (CNS) disorders linked to subsequent epilepsy. We examined data from a sample of older veterans (>65 years) receiving care from the Veterans Health Administration during fiscal year 2000. We compared individuals with new-onset epilepsy and individuals without epilepsy to examine the extent to which psychiatric disorders were associated with new-onset epilepsy; this analysis controlled for demographic and premorbid neurological risk factors previously associated with new-onset epilepsy. Premorbid psychiatric conditions occurred at higher rates in the epilepsy versus nonepilepsy groups, foremost including depression (17% vs 12%), anxiety (12% vs 8%), psychosis (12% vs 5%), and substance abuse (8% vs 4%). However, in the final model, only psychosis (OR=1.4, CI 1.2-1.6) was significantly associated with epilepsy when controlling for neurological disorders and psychiatric conditions (e.g., stroke, dementia, brain tumor, head injury).

New-onset epilepsy risk factors in older veterans.

OBJECTIVES: To identify risk factors for new-onset geriatric epilepsy that may trigger clinicians to consider a differential diagnosis of epilepsy at symptom onset. DESIGN: Retrospective cohort study. SETTING: National Veterans Affairs (VA) databases. PARTICIPANTS: Veterans aged 66 and older in fiscal year 2000 (FY00) who received VA care in FY99 and FY00. Individuals with new-onset epilepsy based on a validated algorithm constituted the epilepsy cohort (n=1,843), and individuals without epilepsy constituted the geriatric cohort (n=1,023,376). MEASUREMENTS: Age, sex, and race were derived from VA databases. Clinical conditions associated with new-onset geriatric epilepsy (e.g., cerebrovascular disease, dementia, brain tumor) and stroke risk-factors (e.g., hypertension, diabetes mellitus, cardiovascular disease) were identified using validated International Classification of Diseases, Ninth Revision, Clinical Modification, codes before epilepsy onset (epilepsy cohort) and in FY00 (geriatric cohort). RESULTS: Multivariable logistic regression analysis indicated that patients with cerebrovascular disease (odds ratio (OR)=3.50, 95% confidence interval (CI)=3.13-3.91), cerebrovascular disease and dementia (OR=4.14, 95% CI=3.46-4.96), brain tumor (OR=2.14, 95% CI=1.46-3.13), head injury (OR=2.11, 95% CI=1.41-3.14), and other central nervous system (CNS) conditions (OR=1.57, 95% CI=1.32-1.88) were more likely to experience new-onset epilepsy. Statin prescription (OR=0.64, 95% CI=0.56-0.73), older age (> or =85 vs 66-74, OR=0.66, 95% CI=0.50-0.87), obesity (OR=0.74, 95% CI=0.62-0.87), and hypercholesterolemia (OR=0.87, 95% CI=0.76-0.98) were associated with a lower likelihood of epilepsy. CONCLUSION: These data suggest greater epilepsy risk for older individuals with CNS insult and an additive effect of cerebrovascular disease and dementia. The statin finding requires further exploration but points to a possible target for prevention of geriatric epilepsy.