Injury of the Ascending Reticular Activating System in Patients With Fatigue and Hypersomnia Following Mild Traumatic Brain Injury

Abstract

We report on patients with post-traumatic fatigue and hypersomnia who showed injury of the lower portion of the ascending reticular activating system (ARAS) between the pontine reticular formation (RF) and the intralaminar thalamic nucleus (ILN) following mild traumatic brain injury (TBI), using diffusion tensor tractography (DTT).Two patients with mild TBI resulting from a car accident were enrolled in this study. Patient 1 was a 51-year-old woman showed abnormalities as 6.9 (cut off: 3.7 points) and 18 (cut off: 10) on the Fatigue Severity Scale and the Epworth Sleepiness Scale at 11 months after onset. Patient 2 was a 64-year-old woman who revealed abnormalities on the Fatigue Severity Scale and the Epworth Sleepiness Scale with 6.8 and 19 at 3 months after onset.In both patients, the upper ARAS in which the neural connectivity of the ILN to the cerebral cortex did not show significant abnormalities. However, we observed the narrowing of the left dorsal lower ARAS between the pontine RF and the ILN in both patients and the tearing (patient 1) and narrowing (patient 2) of the left ventral lower ARAS between the pontine RF and the hypothalamus.Injuries of the dorsal and ventral lower ARAS were demonstrated in patients with fatigue and hypersomnia following mild TBI. We believe that these injuries of the ARAS might be a pathogenetic mechanism of fatigue and hypersomnia in patients with TBI.

Diagnostic History of Traumatic Axonal Injury in Patients with Cerebral Concussion and Mild Traumatic Brain Injury

“…Most problems in diagnosis of TAI in patients with concussion or mild TBI have originated from this insensitivity of conventional CT and MRI. By contrast, since development of DTI, many studies have detected TAI lesions in patients with mild TBI who showed normal conventional CT or MRI [6][7][8][9][10][11][12][13][14]. Based on these results, normal conventional CT or MRI findings in patients with concussion or mild TBI is not an indication that the patient's brain is in a normal state without TAI lesions, therefore, conventional CT and MRI should not be mainly used for diagnosis of TAI in patients with concussion or mild TBI [9,34].…”

“…Regarding the demonstration of TAI in live human patients with concussion or mild TBI, in 2002, Arfanakis et al [6] reported on TAI lesions in patients with mild TBI using DTI for the first time. Subsequently, TAI has been demonstrated in patients with concussion or mild TBI in hundreds of studies [6][7][8][9][10][11][12][13][14].…”

“…Neural axons in the white matter appear to be particularly vulnerable to diffuse head injury due to the mechanical loading of the brain during TBI [23,24]. TAI is defined as tearing of axons due to indirect shearing forces during acceleration, deceleration and rotation of the brain, or direct head trauma [6][7][8][9][10][11][12][13][14][25][26][27][28].…”

“…With the development of DTI in the 1990's, many studies have demonstrated the usefulness of DTI in detection of TAI and TAI lesions in live animals and in human brain with concussion or mild TBI [6][7][8][9][10][11][12][13][14]. In 2007, Mac Donald et al [44], who demonstrated the usefulness of DTI for diagnosis of TAI in a mouse model of mild TBI which showed normal findings on conventional MRI, concluded that DTI is really sensitive for detection of TAI and conventional MRI is not as sensitive as DTI for axonal injury.…”

“…Since the development of diffusion tensor imaging (DTI), many studies have demonstrated traumatic axonal injury (TAI) lesions in patients with concussion or mild TBI [6][7][8][9][10][11][12][13][14]. TAI is a more severe TBI subtype than concussion or mild TBI and use of TAI is rare in Korea, thus there has been significant debate and confusion in the clinical field of Korea (Table 1).…”