Despite increased awareness, a comprehensive understanding of the acute and chronic effects of mTBIs on central nervous system structure and function remains incomplete. Post Traumatic Headache (PTH) is one of the most common symptoms following mTBI and typically develops within 14 days to 3 months after the head injury. PTH incapacitates children in their daily activities (i.e., school, exercise, etc.), and mot importantly, may increase the risk for developing long-term disorders. Although the underlying mechanism remains unknown, PTH may be continuous or evoked/exacerbated by stress (physical or cognitive) indicating that PTH involves multiple brain systems and regions involved in autonomic function. In addition, neuroinflammatory processes may be maintaining/facilitating-sensitized states within these systems. To characterize the autonomic dysfunction in patients with PTH we propose a series of primary and secondary outcomes measures;
(Aim 1) To Evaluate brain network alterations in PTH. We hypothesize to find functional and structural alterations in key regions of the autonomic nervous system, which exacerbate PTH.
(Aim 2) To Evaluate Alterations in Regional Cerebral Blood Flow (rCBF). We hypothesize that patients with PTH exhibit alterations in basal rCBF and cerebrovascular responses to physical and cognitive stress, suggestive of a dysfunction in autonomic tone. Supporting secondary outcome measures will include;
(Aim 3) Autonomic and psychological Markers: To Correlate Alterations in brain function with autonomic and Psychological Markers. We hypothesize that patients with PTH+ exhibit alterations in autonomic tone and psychological trait (anxiety) that contributes to the maintenance of headache related changes and that measures of pain related fear correlate with remission or resistance to headache chronification.
(Aim 4) Inflammatory Markers: To Correlate Alterations in brain function and structure (white matter tracts in the brain and trigeminal system with Inflammatory Markers in PTH: We hypothesize that mTBIs induce changes in inflammatory molecules (cytokines) in the periphery (site of head injury) and in the central nervous system and that elevation of pro-inflammatory cytokines (e.g., IL-6) may drive or maintain PTH. Our group has extensive experience in the field of migraine imaging and has the necessary clinical and research personnel, access to patients, and imaging facilities to complete the proposed study.
Headaches are common following even mild head injuries (i.e., concussions) and compromise activities of daily living in children. Currently, there is no clear understanding of the mechanisms that produce these post- traumatic headaches (PTH). Using high field functional magnetic resonance imaging (fMRI), we will investigate whether PTH result from alterations in brain regions that control autonomic function or abnormalities in cerebral blood flow (CBF) and how psychological changes may persist in these patients. We will also analyze whether brain changes correlate with inflammatory molecules induced by the injury that may persist in patients with PTH. These markers may have use in the clinic to use these markers define which patients may have a risk to chronify and those that will rapidly recover.
| Rosenthal, Perry; Borsook, David; Moulton, Eric A (2016) Oculofacial Pain: Corneal Nerve Damage Leading to Pain Beyond the Eye. Invest Ophthalmol Vis Sci 57:5285-5287 |
