before the introduction of diffusion tensor imaging ( dti ) , accurate evaluation of the ascending reticular activating system ( aras ) in the live human brain was limited .
recently , diffusion tensor tractography ( dtt ) , which is derived from dti , has enabled 3-dimensional reconstruction and estimation of the aras in the human brain . as a result
, a few recent studies using dtt have reported on injury of the aras in patients with severe traumatic brain injury ( tbi ) . however , no study on injury of the aras in patients with mild tbi has been reported .
the pathogenetic mechanism of post - traumatic fatigue and hypersomnia has not been clearly elucidated , although several studies have suggested an injury of the brainstem or aras . in the present study , using dtt , we report on patients with post - traumatic fatigue and hypersomnia who showed injury of the dorsal ( between the pontine reticular formation [ rf ] and the intralaminar thalamic nucleus [ iln ] ) and ventral ( between the pontine rf and the hypothalamus ) lower portion of the aras following mild tbi .
two patients were enrolled according to the following inclusion criteria : ( 1 ) loss of consciousness ( loc ) for 30 min or less , post - traumatic amnesia ( pta ) for < 24  h and glasgow coma scale ( gcs ) score of 13 to 15 recorded 30 min postinjury or later upon presentation for health care , ( 2 ) notify hypersomnia and fatigue since the onset of tbi , ( 3 ) no visible lesion on t1-weighted , t2-weighted , fluid attenuated inversion recovery , and t2-weighted gradient recall echo images , and ( 4 ) no history of previous head trauma .
all patients provided signed , informed consent , and yeungnam university hospital institutional review board approved the study protocol .
patient 1 was a 51-year - old woman who had suffered head trauma resulting from a car accident . while driving her sedan , the driver side of her car collided with a mini - bus ; consequently , her head hit the car seat .
the patient showed loc ( 5  min ) or pta ( 10  min ) at the time of head trauma , and her gcs was 15 when she arrived at the hospital .
at the time of dti scanning ( 11 months after onset ) , she showed abnormalities as 6.9 ( cut off : 3.7 points ) and 18 ( cut off : 10 ) , respectively , on the fatigue severity scale and the epworth sleepiness scale .
patient 2 was a 64-year - old woman who had suffered head trauma resulting from a car accident .
while driving in a passenger seat of a sedan , her car was hit from front by a sedan . as a result ,
her gcs score was 15 when she arrived at the hospital . at the time of dti scanning ( 3 months after onset ) , she showed abnormalities on the fatigue severity scale and the epworth sleepiness scale with 6.8 ( cut off : 3.7 points ) and 19 ( cut off : 10 ) , respectively .
diffusion tensor imaging data were acquired at 11 months ( patient 1 ) and 3 months ( patient 2 ) after onset of head trauma using a 1.5  t with 32 noncollinear diffusion sensitizing gradients by single - shot echo - planar imaging .
imaging parameters were as follows : acquisition matrix  =  96    96 ; reconstructed to matrix  =  192    192 ; field of view  =  240    240  mm ; tr  =  10,398 ms ; te  =  72 ms ; parallel imaging reduction factor  =  2 ; echo - planar imaging factor  =  59 ; b  =  1000  s / mm ; and a slice thickness of 2.5  mm .
the oxford centre for functional magnetic resonance imaging of the brain ( fmrib ) software library was used for analysis of dti data .
fmrib diffusion software with routines option ( 0.5  mm step lengths , 5000 streamline samples , curvature thresholds  =  0.2 ) was used for fiber tracking .
three portions of the aras were reconstructed by selection of fibers passing through region of interest ( roi ) as follows : the dorsal lower aras , between the pontine rf ( roi 1 ) and the iln ( roi 2 ) , the ventral lower aras , between the pontine rf ( roi 1 ) and the hypothalamus ( roi 2 ) , and the upper aras , in which the neural connectivity of the iln ( roi 1 ) to the cerebral cortex was analyzed . the tract volume and the narrowest area of dorsal and ventral lower aras were measured by counting voxels . 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 .
the tract volume of the dorsal and ventral lower aras were 280/322 ( right ) and 149/172 ( left ) voxels in the patient 1 , and 320/201 ( right ) and 185/49 ( left ) voxels in the patient 2 .
in addition , compared with the right hemisphere ( 100% ) , the narrowest area of left hemisphere in the dorsal and ventral lower aras on an axial slice were as follows  the patient 1 : 7 voxels ( 29.2% , right : 24 voxels ) and 11 voxels ( 26.8% , right : 41 voxels ) , and the patient 2 : 15 voxels ( 33.3% ) , right : 45 voxels ) and 3 voxels ( 15% , right:20 voxels ) ( figure 1 ) .
( a ) t2-weighted brain mr images at 11 months ( patient 1 ) and 3 months ( patient 2 ) after onset show no abnormal lesion .
the narrowing ( red arrows ) of the left dorsal lower ascending reticular activating system ( aras ) between the pontine reticular formation and intralaminar thalamic nucleus in both patients , and the tearing ( patient 1 , green arrow ) and narrowing ( patient 2 , green arrows ) of the left ventral lower aras between the pontine reticular formation and the hypothalamus are observed compared with the right side of each patient and both sides of a normal subject ( 45 year - old woman ) .
aras  =  ascending reticular activating system , dtt  =  diffusion tensor tractography , iln  =  intralaminar thalamic nucleus , mr  =  magnetic resonance , prf  =  pontine reticular formation .
two patients were enrolled according to the following inclusion criteria : ( 1 ) loss of consciousness ( loc ) for 30 min or less , post - traumatic amnesia ( pta ) for < 24  h and glasgow coma scale ( gcs ) score of 13 to 15 recorded 30 min postinjury or later upon presentation for health care , ( 2 ) notify hypersomnia and fatigue since the onset of tbi , ( 3 ) no visible lesion on t1-weighted , t2-weighted , fluid attenuated inversion recovery , and t2-weighted gradient recall echo images , and ( 4 ) no history of previous head trauma .
all patients provided signed , informed consent , and yeungnam university hospital institutional review board approved the study protocol .
patient 1 was a 51-year - old woman who had suffered head trauma resulting from a car accident . while driving her sedan , the driver side of her car collided with a mini - bus ; consequently , her head hit the car seat .
the patient showed loc ( 5  min ) or pta ( 10  min ) at the time of head trauma , and her gcs was 15 when she arrived at the hospital .
at the time of dti scanning ( 11 months after onset ) , she showed abnormalities as 6.9 ( cut off : 3.7 points ) and 18 ( cut off : 10 ) , respectively , on the fatigue severity scale and the epworth sleepiness scale .
patient 2 was a 64-year - old woman who had suffered head trauma resulting from a car accident .
while driving in a passenger seat of a sedan , her car was hit from front by a sedan . as a result ,
her gcs score was 15 when she arrived at the hospital . at the time of dti scanning ( 3 months after onset )
, she showed abnormalities on the fatigue severity scale and the epworth sleepiness scale with 6.8 ( cut off : 3.7 points ) and 19 ( cut off : 10 ) , respectively .
diffusion tensor imaging data were acquired at 11 months ( patient 1 ) and 3 months ( patient 2 ) after onset of head trauma using a 1.5  t with 32 noncollinear diffusion sensitizing gradients by single - shot echo - planar imaging .
imaging parameters were as follows : acquisition matrix  =  96    96 ; reconstructed to matrix  =  192    192 ; field of view  =  240    240  mm ; tr  =  10,398 ms ; te  =  72 ms ; parallel imaging reduction factor  =  2 ; echo - planar imaging factor  =  59 ; b  =  1000  s / mm ; and a slice thickness of 2.5  mm .
the oxford centre for functional magnetic resonance imaging of the brain ( fmrib ) software library was used for analysis of dti data .
fmrib diffusion software with routines option ( 0.5  mm step lengths , 5000 streamline samples , curvature thresholds  =  0.2 ) was used for fiber tracking .
three portions of the aras were reconstructed by selection of fibers passing through region of interest ( roi ) as follows : the dorsal lower aras , between the pontine rf ( roi 1 ) and the iln ( roi 2 ) , the ventral lower aras , between the pontine rf ( roi 1 ) and the hypothalamus ( roi 2 ) , and the upper aras , in which the neural connectivity of the iln ( roi 1 ) to the cerebral cortex was analyzed .
the tract volume and the narrowest area of dorsal and ventral lower aras were measured by counting voxels . 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 .
the tract volume of the dorsal and ventral lower aras were 280/322 ( right ) and 149/172 ( left ) voxels in the patient 1 , and 320/201 ( right ) and 185/49 ( left ) voxels in the patient 2 .
in addition , compared with the right hemisphere ( 100% ) , the narrowest area of left hemisphere in the dorsal and ventral lower aras on an axial slice were as follows  the patient 1 : 7 voxels ( 29.2% , right : 24 voxels ) and 11 voxels ( 26.8% , right : 41 voxels ) , and the patient 2 : 15 voxels ( 33.3% ) , right : 45 voxels ) and 3 voxels ( 15% , right:20 voxels ) ( figure 1 ) .
( a ) t2-weighted brain mr images at 11 months ( patient 1 ) and 3 months ( patient 2 ) after onset show no abnormal lesion . ( b )
the narrowing ( red arrows ) of the left dorsal lower ascending reticular activating system ( aras ) between the pontine reticular formation and intralaminar thalamic nucleus in both patients , and the tearing ( patient 1 , green arrow ) and narrowing ( patient 2 , green arrows ) of the left ventral lower aras between the pontine reticular formation and the hypothalamus are observed compared with the right side of each patient and both sides of a normal subject ( 45 year - old woman ) .
aras  =  ascending reticular activating system , dtt  =  diffusion tensor tractography , iln  =  intralaminar thalamic nucleus , mr  =  magnetic resonance , prf  =  pontine reticular formation .
in the present study , using dtt , we evaluated the 3 portions of the aras : the upper aras in which the neural connectivity of the intralaminar thalamic nucleus to the cerebral cortex , the dorsal lower aras , between the pontine rf and the iln , and the ventral lower aras , between the pontine rf and the hypothalamus .
we found that the dorsal and ventral lower aras was torn or narrowed in both patients .
the post - traumatic fatigue and hypersomnia in these patients might be mainly attributed to the injury of the left dorsal and ventral lower aras . since introduction of dti ,
a few studies have reported on injury of the aras in patients with tbi . in 2013 ,
edlow et al ( 2013 ) reported on a patient with coma following severe tbi who showed complete disruption of white matter pathways connecting brainstem arousal nuclei to the basal forebrain and thalamic nuclei , and partial disruption of the pathways connecting the thalamus and basal forebrain to the cerebral cortex .
jang et al ( 2015 ) recently demonstrated recovery of the injured lower portion of the aras between the pontine rf and the iln in a patient with severe tbi . on the other hand , descending reticular activating system , which is involved in the generation of movement using mediating the spinal motoneurons , could also be related to the state of consciousness . in 2013 , tapia et al suggested that arousal state was related to muscular activation which was mediated by the descending reticular activating system .
therefore , to the best of our knowledge , this is the first study to demonstrate injury of the lower portion of the aras between the pontine rf and the iln in patients with mild tbi .
first , because it is a case report , this study is limited ; therefore , conduct of further studies comprising a large number of patients would be necessary .
second , despite being a powerful anatomic imaging tool , because regions of fiber complexity and crossing can prevent full reflection of the underlying fiber architecture , dti may underestimate or overestimate the fiber tracts . in conclusion , this study demonstrated injuries of the dorsal and ventral lower portions of the aras 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 .
 abstractwe 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 . 
INTRODUCTION
CASE REPORT
Subjects
Diffusion Tensor Imaging
DISCUSSION