Microvascular and large vein abnormalities in young patients after mild head trauma and associated fatigue: A brain SPECT evaluation and posture dependence modeling

Abstract

ObjectiveMRI and CT scans are usually normal in mild traumatic brain injury (mTBI) although 15–20% of such patients suffer for months from fatigue, headache, anxiety, sleep and other disorders. mTBI is suspected to be a cerebrovascular injury, similar to moderate and severe TBI. Brain SPECT is more sensitive and shows perfusion abnormalities immediately after mTBI. This work explores the perfusion abnormalities for young patients suffering from fatigue several months after mTBI. Patients and methodsTwelve mTBI patients (age:8–36 yr, 4 male) with no history of fatigue prior to trauma were prospectively studied following onset of fatigue 6–12 months after mTBI utilizing 99 m-Tc ECD brain SPECT with early and delayed radiotracer imaging. ResultsThe perfusion pattern in the mTBI + fatigue group included left hemispheric deficits in frontal lobes (early phase: 15.2 ± 4.2%, delayed phase: 9.9 ± 2.2%) and medial temporal lobes (early phase 11.2 ± 3.7%, delayed phase: 9.0 ± 2.3%). Seven patients additionally showed excess tracer accumulation in the parenchyma surrounding internal jugular bulb inferior to temporal lobe. This was modeled as due to increased cellular permeability from TBI induced oxidative stress affecting endothelial tight junctions and consequent tracer leakage across jugular bulbs. Prolonged posture changes from erect to supine position during imaging increase jugular cross-sectional area and venous wall pressure as has been observed in other disease processes and seem to be responsible for tracer leakage from jugular bulbs in our study. ConclusionThis work supports an oxidative stress and BBB disruption model for mTBI. The frontal and temporal lobe perfusion deficits are attributed to anatomical vulnerabilities of these lobes. During a mild TBI both of these lobes are susceptible to grazing impacts with underlying bony ridges. We propose a relation between mTBI and fatigue arising from oxidative stress in mTBI affecting ATP generation and altering endothelial homeostasis for both micro-and-large vasculatures. The tracer leakage observed around jugular veins is due to posture induced changes in venous cross-sections and wall pressure as well as from compromised endothelium post TBI induced oxidative stress.