Contents lists available at ScienceDirect Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro Microvascular and large vein abnormalities in young patients after mild head trauma and associated fatigue: A brain SPECT evaluation and posture dependence modeling Tiffany Crider a,1 , Derrick Eng b,1 , Pooja R. Sarkar c , Janet Cordero d , John Claude Krusz e , Subhendra N. Sarkar d, ⁎ a HackensackUMC Palisades, North Bergen, NJ, United States b Orange Regional Medical Center, Middletown, NY, United States c Touro College of Osteopathic Medicine, Middletown, NY, United States d Department of Radiologic Technology & Medical Imaging, New York City College of Technology, City University of New York, Brooklyn, NY, United States e Anodyne Headache, Pain Care & Well-Being, Dallas, TX, United States ARTICLE INFO Keywords: Mild TBI Fatigue Mild head trauma Brain SPECT Vascular injury Temporal lobe Cerebral perfusion MR venogram in TBI ABSTRACT Objective: MRI 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 suf- fering from fatigue several months after mTBI. Patients and methods: Twelve 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. Results: The 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. Conclusion: This 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. 1. Introduction Mild traumatic brain injury (mTBI) is common affecting approxi- mately 1.2 M Americans every year [1]. Most patients with mTBI have impaired or absent cerebral autoregulation within 48 h of injury [2]. Still neurocognitive deficits are reported only in 10% of cases, sig- nificantly underestimating the long- term burdens associated with it [3–6]. mTBI is defined by the Mild Traumatic Brain Injury Committee of the brain injury interdisciplinary special interest group of the https://doi.org/10.1016/j.clineuro.2018.05.019 Received 18 March 2018; Received in revised form 28 April 2018; Accepted 17 May 2018 ⁎ Correspondence at: Department of Radiologic Technology & Medical Imaging, New York City College of Technology, City University of New York, 300 Jay St, Brooklyn, NY, 11201, United States. 1 Co-first authors with equal contributions. E-mail address: ssarkar@citytech.cuny.edu (S.N. Sarkar). Clinical Neurology and Neurosurgery 170 (2018) 159–164 Available online 18 May 2018 0303-8467/ © 2018 Elsevier B.V. All rights reserved. T