Traumatic brain injury (TBI) is a common neurological disorder in the present era. Neural axons in the white matter are known to be vulnerable to head trauma due to mechanical loading of the brain during TBI.[1–3] Traumatic axonal injury (TAI) is the tearing of axons due to indirect shearing forces during acceleration, deceleration, and rotation of the brain, or the result of direct head trauma.[3,4–7] TAI has been demonstrated in many pathological studies by examining animal brain or post-mortem human brain.[4,5,8] However, diagnosis of TAI in living patients has been limited because of the insufficient sensitivity of conventional brain magnetic resonance imaging (MRI) for detection of TAI in subjects with mild TBI.[3,7,9]
Since the development of diffusion tensor imaging (DTI), which provides invaluable information about subcortical white matter that cannot be obtained via conventional MRI, TAI has been demonstrated in many DTI-based studies of TBI patients whose conventional brain MRI results are negative.[9–16] Injury mechanisms for TAI in these patients have been associated with motor vehicle accidents (predominant mechanism), sport accidents, falling objects, falls, and so on.[9,12–16] However, very little has been reported on the detection of TAI resulting from violence, even though it is important medically and legally.
In this study, we report on a patient who, following head trauma due to violence showed extensive TAI of various neural tracts on DTI.
2 Case report
A 42-year-old male patient presented after experiencing head trauma due to violence. His face was hit several times by 2 men. Subsequently, 1 of the men kicked the right side of the patient's head, after which the patient's left parietal area hit to the ground while falling. The patient experienced loss of consciousness and post-traumatic amnesia for 5 hours. The patient's Glasgow Coma Scale score was 15 when he arrived at the emergency room of a university hospital. He did not have any medical history of neurological or psychiatric disease, and no previous incidents of head trauma. After the head trauma, he experienced mild motor weakness of the left upper and lower extremities, mild articulation difficulties, cognitive dysfunction including memory impairment, and excessive daytime sleepiness. Ten days after the head trauma, he was admitted to the rehabilitation department of a university hospital. He showed mild left hemiparesis (5/4), mild dysarthria, mild cognitive abnormality (Clinical Dementia Rating = 0.5, range 0∼3; higher score indicates more abnormality), and mild sleeping abnormality (Epworth Sleepiness Scale = 12, range 10∼24; higher score indicates more sleepiness).[17,18] No specific lesion was observed on brain MRI (T1-weighted, T2-weighted, and fluid-attenuated inversion recovery images) and electromyography did not detect any abnormality. Ethical approval for this study was provided by Institutional Review Board of Yeungnam university hospital (YUMC-2015–07–064) and the written informed consent for publication of the case details was obtained from the patient.
The DTI data were acquired 10 days after TBI onset by using a 6-channel head coil on a 1.5 T Philips Gyroscan Intera (Philips, Best, Netherlands) with single-shot echo-planar imaging. For each of the 32 non-collinear diffusion sensitizing gradients, 67 contiguous slices were acquired parallel to the anterior commissure-posterior commissure line. Imaging parameters were as follows: acquisition matrix = 96 × 96, reconstructed to matrix = 192 × 192, field of view = 240 mm × 240 mm, TR = 10,398 ms, TE = 72 ms, parallel imaging reduction factor (SENSE factor) = 2, echo-planar imaging factor = 59 and b = 1000 s/mm2, NEX = 1, and slice thickness = 2.5 mm.
2.1.1 Reconstruction of the corticospinal tract (CST), cingulum, and fornix
Fiber tracking was performed by using the fiber assignment continuous tracking (FACT) algorithm implemented within the DTI task card software (Philips Extended MR WorkSpace 2.6.3, Philips, Amsterdam, Netherlands). Each DTI replication was intra-registered to the baseline “b0” images to correct for residual eddy-current image distortions and head motion effects by using a diffusion registration package (Philips Medical Systems, Amsterdam, Netherlands) (threshold fractional anisotropy = 0.15, angle = 27). For reconstruction of the CST, the seed region of interest (ROI) was placed on the anterior blue portion of the upper pons on the axial image of the color map, and the second ROI was placed on the anterior blue portion of the lower pons on the axial image of the color map. For analysis of the cingulum, the seed and target ROI were placed on the middle and posterior portions, respectively, of the cingulum on the color map of coronal images. Fiber tracking for the CST and cingulum was performed by using a fractional anisotropy of <0.15 and a trajectory angle threshold of >27°. For reconstruction of the fornix, the seed ROI was placed at the junction between the body and column of the fornix, and the target ROIs were placed on each side of the crus of the fornix. Fornix fiber tracking was performed by using a fractional anisotropy threshold of >0.2 and a direction threshold <45°.
2.1.2 Reconstruction of the corticobulbar tract (CBT), prefronto-thalamic tract, and lower ventral ascending reticular activating system (ARAS)
The Oxford Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB) Software Library (www.fmrib.ox.ac.uk/fsl) was used to analyze diffusion-weighted imaging data. Affine multi-scale 2-dimensional registration was used to correct for the head motion effects and image distortion due to eddy currents. FMRIB Diffusion Software with the routine option (0.5 mm step lengths, 5000 streamline samples, curvature thresholds = 0.2) was used to reconstruct fiber tracking. For analysis of the CBT, the seed ROI was placed on the lower pons, and the target ROI was placed on the lower portion of the precentral gyrus and in the section at the top of the lateral ventricles. To reconstruct the prefronto-thalamic tract, the seed ROI was placed on the mediodorsal nucleus (MD), and target ROIs were on the dorsolateral prefrontal cortex (DLPFC), the ventrolateral prefrontal cortex (VLPFC), and the orbitofrontal cortex (OFC), respectively. To analyze the lower ventral ARAS, the seed ROI was placed on the pontine reticular formation and the target ROI on the hypothalamus. A threshold of 2 streamlines was applied to the fiber tracking results.
DTT showed the following configurational abnormalities: narrowing of the right CST and the left CBT, narrowing of both cingula, discontinuations in the anterior portion of the fornix and in left fornical crus, narrowing in both lower ventral ARAS, and non-reconstruction of the right dorsolateral prefronto-thalamic tract (Fig. 1B).
In this study, abnormal findings (narrowing, discontinuation, and non-reconstruction) indicative of neural injuries were observed in a patient who suffered head trauma due to violence. The CST and CBT are reported to be mainly involved in motor control of extremities and articulation muscles, respectively.[23,24] The fornix transfers episodic memory, whereas the cingulum and the dorsolateral prefronto-thalamic tract are involved in short-term memory.[25–27] Recently, injury of the lower ventral ARAS, which is connected to the hypothalamus, was reported to result in excessive daytime hypersomnia. The clinical features recorded for the patient in this study appear to be associated with injury of each of those neural tracts as follows: mild left hemiparesis associated with injury of the right CST; mild dysarthria associated with injury of the left CBT; memory impairment associated with injuries of the fornix, both anterior cingula, and the dorsolateral thalamocortical tract; and excessive daytime sleepiness associated with injuries of both lower ventral ARAS. Because no specific lesion was observed on conventional brain MRI of this patient, it appears that the injuries of those neural tracts (i.e., CST, CBT, fornix, cingulum, and dorsolateral thalamocortical tract and lower ventral ARAS) indicate the presence of TAI.[3,4,7,9]
In conclusion, by using DTI, extensive TAI was demonstrated in several neural tracts of a patient with head trauma due to violence. The results suggest that analysis of the neural tracts via DTI can be useful in detection of TAI in patients who show various neurological features following head trauma due to violence. However, DTI has a significant limitation in reconstruction of some neural tracts due to the partial volume effect and crossing fibers, which can prevent full reconstruction of fiber and tract architecture. The individual patients who have been demonstrated TAI using DTI following head trauma were injured by motor vehicle accidents, sport accidents, falling objects, falls, and so on.[9,12–16] By contrast, this is the first study to report TAI following head trauma due to violence as far as we are aware.
Draft writing, editing & Supervision: Jang SH.
Supervision & editing: Kim SH.
Data analysis, Draft writing & editing: Kwon YH.
. Maxwell WL, Povlishock JT, Graham DL. A mechanistic analysis of nondisruptive axonal injury: a review. J Neurotrauma 1997;14:419–40.
. Johnson VE, Stewart W, Smith DH. Axonal pathology in traumatic brain injury
. Exp Neurol 2013;246:35–43.
. Jang SH. Traumatic axonal injury
in mild traumatic brain injury
. In Gorbunoy N, editor. Traumatic brain injury
. 1st ed. InTech; 137–54.
. Povlishock JT. Traumatically induced axonal injury: pathogenesis and pathobiological implications. Brain Pathol 1992;2:1–2.
. Povlishock JT, Christman CW. The pathobiology of traumatically induced axonal injury in animals and humans: a review of current thoughts. J Neurotrauma 1995;12:555–64.
. Hill CS, Coleman MP, Menon DK. Traumatic axonal injury
: mechanisms and translational opportunities. Trends Neurosci 2016;39:311–24.
. Jang SH. Diagnostic history of traumatic axonal injury
in patients with cerebral concussion and mild traumatic brain injury
. Brain Neurorehabil 2016;9:1–8.
. Blumbergs PC, Scott G, Manavis J, et al. Staining of amyloid precursor protein to study axonal damage in mild head injury. Lancet 1994;344:1055–6.
. Shenton ME, Hamoda HM, Schneiderman JS, et al. A review of magnetic resonance imaging and diffusion tensor imaging
findings in mild traumatic brain injury
. Brain Imaging Behav 2012;6:137–92.
. Arfanakis K, Haughton VM, Carew JD, et al. Diffusion tensor mr imaging in diffuse axonal injury. AJNR Am J Neuroradiol 2002;23:794–802.
. Brandstack N, Kurki T, Tenovuo O. Quantitative diffusion-tensor tractography of long association tracts in patients with traumatic brain injury
without associated findings at routine mr imaging. Radiology 2013;267:231–9.
. Seo JP, Jang SH. Injury of the spinothalamic tract in a patient with mild traumatic brain injury
: diffusion tensor tractography study. J Rehabil Med 2014;46:374–7.
. Kim JH, Ahn SH, Cho YW, et al. The relation between injury of the spinothalamocortical tract and central pain in chronic patients with mild traumatic brain injury
. J Head Trauma Rehabil 2015;30:E40–6.
. Jang SH, Kim SY. Injury of the corticospinal tract in patients with mild traumatic brain injury
: a diffusion tensor tractography study. J Neurotrauma 2016;33:1790–5.
. Jang SH, Lee AY, Shin SM. Injury of the arcuate fasciculus in the dominant hemisphere in patients with mild traumatic brain injury
a retrospective cross-sectional study. Medicine 2016;95:e3007.
. Jang SH, Lee HD. Central pain due to spinothalamic tract injury caused by indirect head trauma following a pratfall. Brain Inj 2016;30:933–6.
. Hughes CP, Berg L, Danziger WL, et al. A new clinical scale for the staging of dementia. Br J Psychiatry 1982;6–572.
. Johns MW. Reliability and factor analysis of the epworth sleepiness scale. Sleep 1992;15:376–81.
. Concha L, Gross DW, Beaulieu C. Diffusion tensor tractography of the limbic system. AJNR Am J Neuroradiol 2005;26:2267–74.
. Jang SH, Seo JP. The anatomical location of the corticobulbar tract at the corona radiata in the human brain: diffusion tensor tractography study. Neurosci Lett 2015;590:80–3.
. Jang SH, Yeo SS. Thalamocortical connections between the mediodorsal nucleus of the thalamus and prefrontal cortex in the human brain: a diffusion tensor tractographic study. Yonsei Med J 2014;55:709–14.
. Jang SH, Seo WS, Kwon HG. Post-traumatic narcolepsy and injury of the ascending reticular activating system. Sleep Med 2016;17:124–5.
. York DH. Review of descending motor pathways involved with transcranial stimulation. Neurosurgery 1987;20:70–3.
. Liegeois F, Tournier JD, Pigdon L, et al. Corticobulbar tract changes as predictors of dysarthria in childhood brain injury. Neurology 2013;80:926–32.
. Cummings JL. Frontal-subcortical circuits and human behavior. Arch Neurol 1993;50:873–80.
. Papez JW. A proposed mechanism of emotion. J Neuropsychiatry Clin Neurosci 1995;7:103–12.
. Bush G, Luu P, Posner MI. Cognitive and emotional influences in anterior cingulate cortex. Trends Cogn Sci 2000;4:215–22.
. Parker GJ, Alexander DC. Probabilistic anatomical connectivity derived from the microscopic persistent angular structure of cerebral tissue. Philos Trans R Soc Lond B Biol Sci 2005;360:893–902.