Background and Rationale: Vestibular symptoms (vertigo, unsteadiness, dizziness, or gait imbalance) are among the most common and pernicious symptoms of mild traumatic brain injury (mTBI). When present, they delay or reduce the likelihood of affected individuals returning to military duty, athletic activities, or work. State-of-the-art therapeutic interventions are symptom-focused because there are no clear models of pathophysiological mechanisms that may be causing post-mTBI vestibular symptoms. As a result, at least 20% of patients remain chronically ill, often disabled, even with expert care. The leading mechanistic hypotheses include failure to compensate for peripheral vestibular injury (possibly otolith damage) and diffuse axonal injury. Psychosocial factors may play a role as well, but there are no specific processes that link these to post-mTBI vestibular morbidity.Various lines of research on chronic vestibular symptoms in patients without TBI have consolidated around a novel model of illness. Experts have begun to move away from a focus on the putative long-term structural effects of acute peripheral or central deficits to a model of illness that describes the onset of chronic symptoms as a dynamic interaction of clinically observable physiological and psychological processes that produce functional changes in locomotor control (stiffening of posture and gait) and reweighting of multi-modal space-motion information processing to favor visual stimuli (visual dependence). Evidence from researchers worldwide has identified psychological risk factors that interact with acute injuries (vestibular, headache, autonomic, or cardiac disorders and psychological distress) to promote a transition from acute to chronic symptoms maintained by persistent postural stiffening and visual dependence. The recently defined vestibular disorder, persistent postural-perceptual dizziness (PPPD), embodies these new concepts.Research Team, Specific Aims, and Methods: The research team behind this proposal combines pioneers in the study of phenomenological, physiological, psychological, and brain imaging markers of PPPD and investigators with established track records of clinical care and research in TBI to test the hypothesis that mechanisms underlying the development of PPPD after acute events may be applicable to patients who develop chronic vestibular symptoms after mTBIs. In this three-site, prospective observational study, we intend to test that hypothesis by applying the methods that we developed to measure physiological functioning, psychological state, and alterations in brain structure and function in patients with PPPD to patients with post-mTBI vestibular symptoms. We will assess patients 2-8 weeks after injury and again 6-8 months after injury and compare them to healthy controls to pursue these Specific Aims:1. Identify physiological and psychological factors that predispose, precipitate, promote, and perpetuate chronic disability due to vestibular symptoms in patients with histories of mTBIs, including the personality trait of neuroticism, plus post-acute state anxiety, stiffened postural control, and visual dependence and their interactions with structural injuries. From these variables, we intend to construct a clinical profile of patients assessed at 2-8 weeks who are at risk for disability due to vestibular symptoms at 6-8 months.2. Utilize advanced neuroimaging methods to identify alterations in brain structure and function that are associated with clinical variables that predict disabling vestibular symptoms in patients with histories of mTBIs.To analyze data from Aim 1, we will construct linear regression models with chronic dizziness handicap as the dependent variable and the physiological, psychological, and structural factors as predictors. Then, we will construct receiver operating characteristics curves to identify the combination of post-acute clinical variables that is most predictive of chronic disability. To analyze data from Aim 2, we will use the advanced MRI image processing tools that we applied to studies of patients with chronic dizziness in our preliminary investigations.Impact and Military Benefit: This effort differs from previous attempts in two important ways: (1) we will be applying specific mechanistic hypotheses to this problem, and (2) we will be pursuing associations with underlying brain processes. Despite the high-tech methods of Aim 2, our ultimate goal is to improve the care of active duty Service members, Veterans, and civilians whose acute and early post-acute care may be necessarily (even desirably) low-tech; hence, our focus in Aim 1 on clinically assessable metrics. We will study civilian cohorts, as we did in our preliminary work, but we expect our next steps to involve clinical trials of improved triage protocols and novel therapies to mitigate, even prevent, the transition from acute to chronic symptoms. We intend these trials to occur in military, Veterans Affairs, and civilian medical facilities, including those in operational environments.
|Effective start/end date||9/30/18 → 9/29/22|
- Congressionally Directed Medical Research Programs: $1,978,267.00