Download Diagnostic History of Traumatic Axonal Injury in Patients with

Brain Neurorehabil. 2016 Sep;9(2):e1
https://doi.org/10.12786/bn.2016.9.e1
pISSN 1976-8753·eISSN 2383-9910
Review
Brain & NeuroRehabilitation
Diagnostic History of Traumatic
Axonal Injury in Patients with Cerebral
Concussion and Mild Traumatic Brain
Injury
Sung Ho Jang
Received: May 26, 2016
Accepted: May 26, 2016
Highlights
Correspondence to
Sung Ho Jang
Department of Physical Medicine and
Rehabilitation, Yeungnam University College of
Medicine, 170 Hyunchung-ro, Nam-gu, Daegu
42415, Korea.
Tel: +82-53-620-3269
Fax: +82-53-620-4508
E-mail: [email protected]
• Cerebral concussion and mild traumatic brain injury (TBI) have been used interchangeably,
although the two terms have different definitions.
• Traumatic axonal injury (TAI) is a more severe subtype of TBI than concussion or mild TBI.
• In this review article, we reviewed the history of TAI in patients with concussion and mild TBI.
Copyright © 2016 Korea Society for Neurorehabilitation
i
Brain Neurorehabil. 2016 Sep;9(2):e1
https://doi.org/10.12786/bn.2016.9.e1
pISSN 1976-8753·eISSN 2383-9910
Review
Brain & NeuroRehabilitation
Diagnostic History of Traumatic
Axonal Injury in Patients with Cerebral
Concussion and Mild Traumatic Brain
Injury
Sung Ho Jang
Department of Physical Medicine and Rehabilitation, Yeungnam University College of Medicine, Daegu, Korea
Received: May 26, 2016
Accepted: May 26, 2016
ABSTRACT
Correspondence to
Sung Ho Jang
Department of Physical Medicine and
Rehabilitation, Yeungnam University College of
Medicine, 170 Hyunchung-ro, Nam-gu, Daegu
42415, Korea.
Tel: +82-53-620-3269
Fax: +82-53-620-4508
E-mail: [email protected]
Cerebral concussion and mild traumatic brain injury (TBI) have been used interchangeably,
although the two terms have different definitions. Traumatic axonal injury (TAI) is a more
severe subtype of TBI than concussion or mild TBI. Regarding the evidence of TAI lesions
in patients with concussion or mild TBI, since the 1960’s, several studies have reported
on TAI in patients with concussion who showed no radiological evidence of brain injury
by autopsy. However, conventional CT and MRI are not sensitive to detection of axonal
injury in concussion or mild TBI, therefore, previously, diagnosis of TAI in live patients
with concussion or mild TBI could not be demonstrated. With the development of diffusion
tensor imaging (DTI) in the 1990’s, in 2002, Arfanakis et al. reported on TAI lesions in live
patients with mild TBI using DTI for the first time. Subsequently, hundreds of studies have
demonstrated the usefulness of DTI in detection of TAI and TAI lesions in patients with
concussion or mild TBI. In Korea, the term “TAI” has rarely been used in the clinical field
while diffuse axonal injury and concussion have been widely used. Rare use of TAI in Korea
appeared to be related to slow development of DTI analysis techniques in Korea. Therefore, we
think that use of DTI analysis techniques for diagnosis of TAI should be facilitated in Korea.
Copyright © 2016 Korea Society for
Neurorehabilitation
This is an Open Access article distributed
under the terms of the Creative Commons
Attribution Non-Commercial License (http://
creativecommons.org/licenses/by-nc/4.0/)
which permits unrestricted non-commercial
use, distribution, and reproduction in any
medium, provided the original work is properly
cited.
ORCID
Sung Ho Jang
http://orcid.org/0000-0001-6383-5505
Funding
This work was supported by the National
Research Foundation (NRF) of Korea Grant
funded by the Korean Government (MSIP)
(2015R1A2A2A01004073).
Conflict of Interest
The author has no potential conflicts of
interest to disclose.
Keywords: Diffusion Tensor Imaging; Concussion; Mild Traumatic Brain Injury; Traumatic
Axonal Injury
INTRODUCTION
Traumatic brain injury (TBI) is a major cause of mortality and disability. TBI is classified as
mild, moderate, and severe based on the severity and 70%–90% cases of TBI are classified
as mild TBI [1-3]. The incidence of hospital-treated patients with mild TBI is approximately
100–300/100,000 population, however, the true population-based rate is probably above
600/100,000 when including mild TBI not treated in hospitals [4].
Despite having different definitions, cerebral concussion and mild TBI have been used
interchangeably, therefore the terminology regarding head trauma has caused confusion for
patients and doctors [5]. Since the development of diffusion tensor imaging (DTI), many
studies have demonstrated traumatic axonal injury (TAI) lesions in patients with concussion
http://e-bnr.org
1/8
Diagnostic History of Traumatic Axonal Injury
Table 1. Traumatic brain injury subtypes
Diffuse
Concussion
Traumatic axonal injury/diffusion axonal injury
Blast
Abusive head trauma
Brain & NeuroRehabilitation
Focal
Contusion
Penetrating
Hematoma
- Epidural
- Subarachnoid
- Subdural
- Intraventricular
- Intracerebral
Classification by severity
- Mild
- Moderate
- Severe
or mild TBI [6-14]. 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). We think that reviewing the history of terminology of ‘TAI’ with
concussion and mild TBI would be helpful to clarifying this debate and confusion in Korea.
In this review article, we reviewed the history of TAI in patients with concussion and mild TBI.
DEFINITION OF CEREBRAL CONCUSSION, MILD TBI,
AND TRAUMATIC AXONAL INJURY
Cerebral concussion is defined as a transient, temporary, neurological dysfunction resulting
from application of force to the brain: in detail, cerebral concussion is an acute traumainduced change of mental function generally lasting less than 24 hours and usually recovering
within 2–3 weeks [5,15]. Concussion is not usually associated with visible lesions that can be
detected by conventional CT or MRI [5,16-18].
In 1993, the American Congress of Rehabilitation Medicine defined mild TBI as a
traumatically induced physiological disruption of brain function resulting from the head
being struck or striking an object or an acceleration and deceleration movement of the brain,
as manifested by at least one of the following: any period of loss of consciousness up to 30
minutes; post-traumatic amnesia not exceeding 24 hours and a Glasgow Coma Scale score of
13–15 [16,19-21]. In 1995, Alexander added two more conditions for diagnosis of mild TBI: the
patient has no focal signs and conventional neuroimaging studies are negative [16].
TAI is a more severe subtype of TBI than concussion or mild TBI (Table 1) [22]. 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 [6-14,25-28].
There have been opposing opinions regarding the use of the terms “concussion” and
“mild TBI.” Sharp and Jenkins [18] insisted that mild TBI is not always a benign condition
as its name implies and patients sometimes fail to recover. They proposed that the term
“concussion” should be avoided because it has no clear definition and no pathological
meaning, therefore, at worst it encourages an apathetic diagnostic approach [18]. McMahon
http://e-bnr.org
https://doi.org/10.12786/bn.2016.9.e1
2/8
Diagnostic History of Traumatic Axonal Injury
Brain & NeuroRehabilitation
et al. [29] insisted that the term “mild TBI” is a misnomer for patients with severe postconcussion syndrome. Rapp and Curley [30] reported that mild TBI is a category mistake
because of the heterogeneity of the clinical population and clinical presentations, the absence
of a unitary etiology of post injury deficits, and the complex idiosyncratic time course of the
appearance of these deficits in mild TBI.
PROBLEMS IN DIAGNOSIS OF CEREBRAL CONCUSSION
AND MILD TBI
Cerebral concussion is a transient disorder of brain function without long-term sequelae
[18]. Therefore, patients with concussion should make a complete recovery with no
sequelae. However, a significant proportion of patients with concussion showed sequelae
with a reported incidence of approximately 15% at one year following concussion [31].
These patients were grouped as post-concussion syndrome, which has been regarded as a
psychological problem [31,32]. By contrast, in a recent large multicenter study conducted
in America and England, McMahon et al. [29] reported that 82% of patients reported at
least one post-concussion syndrome and 22.4% of patients were still below functional state
at 12 months after onset. As a result, the opinion that post-concussion syndrome is not a
psychological problem but a physical problem, especially TAI, has been suggested [9,32,33].
Messé et al. [33], who detected TAI lesions using DTI in patients with poor outcome
following mild TBI, suggested that post-concussion syndrome might be a consequence of
TAI. Other researchers have also suggested a possible association between post-concussion
syndrome and TAI [9,32].
It is well-known that conventional CT and MRI are not sensitive to detection of TAI in
patients with concussion or mild TBI [9,34]. 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 [6-14]. 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].
HISTORY OF TRAUMATIC AXONAL INJURY IN
CONCUSSION AND MILD TBI
TAI has been used for several decades as a subtype of TBI [24]. However, in Korea, it has
rarely been used in the clinical field while diffuse axonal injury (DAI) and concussion have
been widely used. Since the middle of the last century, several studies have demonstrated
trauma related axonal injury in the human brain using autopsy [35]. In 1982, Adams et al.
[36], who introduced the term “DAI” by characterizing the extent and distribution of axonal
injury in patients with TBI, defined DAI as the presence of microscopic axonal injury in
the white matter of the cerebral hemisphere, corpus callosum, and brainstem caused by
mechanical forces following head trauma [37,38]. Many subsequent studies have reported
DAI in patients with moderate or severe TBI. Efforts have been made to use terms including
“TAI” or “diffuse TAI” to correct the false term “diffuse” (actual distribution of axonal injury
http://e-bnr.org
https://doi.org/10.12786/bn.2016.9.e1
3/8
Diagnostic History of Traumatic Axonal Injury
Brain & NeuroRehabilitation
lesion is not diffuse but multifocal) and underline the etiology of the axonal injury in trauma
instead of DAI [23,24]. On the other hand, since the 1980’s, many researchers, including
Povlishock, have used the term “TAI” in their histopathological studies [23,25,26,39].
Patients with the traditional definition of DAI are in profound coma from the onset of injury
and usually have a poor outcome [36,40]. Because patients have more restricted patterns
of axonal injury than that seen in the classic DAI with the development of neuroimaging
techniques, the term “TAI” has been used for these more limited injuries: in practice, TAI
has been used in milder cases than DAI [40]. The current tendency is to use one term “TAI”
including DAI and the unification of terms “TAI” and “DAI” is necessary to make clear
confusion and debate for these terms.
Regarding the evidence of TAI lesions in patients with concussion or mild TBI, since the
1960’s, several studies have reported on TAI in patients with concussion who showed no
radiological evidence of brain injury by autopsy [41-43]. One famous study was published by
Lancet in 1994: Blumbergs et al. [42] reported on detection of axonal injury by autopsy in
the brain of 5 patients with concussion, who died of other causes. However, conventional CT
and MRI are not sensitive to detection of axonal injury in concussion or mild TBI, therefore,
previously, diagnosis of TAI in live patients with concussion or mild TBI could not be
demonstrated.
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 [6-14]. 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. 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 [6-14].
DTI AND DTI TRACTOGRAPHY
DTI provides invaluable information about subcortical white matter not available with
conventional CT and MRI, thus development of DTI in the 1990’s has led to a new era for
examination of the subcortical white matter in the live human brain [9,45,46]. DTI is a
sensitive measure of axonal injury that is particularly important for evaluation of small and
subtle brain alterations in patients with mild TBI [9]. DTI was first employed in examination
of white matter pathology in various other brain pathologies, including multiple sclerosis,
stroke, Alzheimer’s disease, and schizophrenia [9]. Regarding mild TBI, Arfanakis et
al. [6], the first researchers to use DTI for examination of TAI in patients with mild TBI,
demonstrated TAI lesions in the subcortical white matter in five patients with mild TBI;
they concluded that DTI is a powerful technique for evaluation of axonal injury in mild TBI.
Subsequently, many researchers including Inglese et al. [7], Niogi et al. [8], and so on have
reported on TAI in patients with mild TBI [6,9]. Recently, in a review article on DTI and mild
TBI, Shenton et al. [9] described DTI as the best imaging technique available for detection of
subcortical white matter damage, therefore, DTI will likely become an important diagnostic
tool for patients with mild TBI, particularly in cases where conventional CT and MRI are
negative.
http://e-bnr.org
https://doi.org/10.12786/bn.2016.9.e1
4/8
Diagnostic History of Traumatic Axonal Injury
Brain & NeuroRehabilitation
DTI tractography, which is reconstructed from DTI data, was developed for visualization and
estimation of the neural tracts in the subcortical white matter of the brain [47]. The main
advantage of DTI tractography is that the whole neural tract, instead of just a portion of the
neural tract, can be evaluated [9]. Therefore, DTI tractography is a promising tool that can be
used to find where damage occurs along the neural tracts [9]. As a result, DTI tractography
can be used for both visualization and quantification of injury of the neural tracts in the
subcortical white matter in a single patient and thus these methods are potentially important
for diagnosis of TAI in patients with concussion or mild TBI [9]. Recently, TAI of various
neural tracts in patients with mild TBI has been demonstrated in tens of studies: these neural
tracts include the corticospinal tract, spinothalamic tract, fornix, cingulum, optic radiation,
and so on (Fig. 1) [10-14].
Fig. 1. Traumatic axonal injuries of various neural tracts in patients with concussion or mild traumatic brain injury.
http://e-bnr.org
https://doi.org/10.12786/bn.2016.9.e1
5/8
Diagnostic History of Traumatic Axonal Injury
Brain & NeuroRehabilitation
CONCLUSION
In this review article, we reviewed history of TAI in cerebral concussion and mild TBI. The
introduction of DTI has enabled accurate diagnosis of TAI in patients with concussion or
mild TBI. Therefore, rare use of TAI in Korea appeared to be related to slow development of
DTI analysis techniques in Korea. Because TAI is a more severe TBI subtype than concussion
and mild TBI, accurate diagnosis of TAI in patients with concussion or mild TBI is important
for the following problems: false diagnosis of TAI with milder TBI subtype (concussion and
mild TBI), delayed diagnosis of TAI, and loss of the critical period for recovery following
TAI. Therefore, we think that use of DTI analysis technique for diagnosis of TAI should be
facilitated in Korea.
REFERENCES
1. Kraus JF, Nourjah P. The epidemiology of mild, uncomplicated brain injury. J Trauma 1988;28:1637-1643.
PUBMED | CROSSREF
2. De Kruijk JR, Twijnstra A, Leffers P. Diagnostic criteria and differential diagnosis of mild traumatic brain
injury. Brain Inj 2001;15:99-106.
PUBMED | CROSSREF
3. Decuypere M, Klimo P Jr. Spectrum of traumatic brain injury from mild to severe. Surg Clin North Am
2012;92:939-957.
PUBMED | CROSSREF
4. Cassidy JD, Carroll LJ, Peloso PM, Borg J, von Holst H, Holm L, et al. Incidence, risk factors and
prevention of mild traumatic brain injury: results of the WHO Collaborating Centre Task Force on Mild
Traumatic Brain Injury. J Rehabil Med 2004;36:28-60.
PUBMED | CROSSREF
5. Anderson T, Heitger M, Macleod AD. Concussion and mild head injury. Pract Neurol 2006;6:342-357.
CROSSREF
6. Arfanakis K, Haughton VM, Carew JD, Rogers BP, Dempsey RJ, Meyerand ME. Diffusion tensor MR
imaging in diffuse axonal injury. AJNR Am J Neuroradiol 2002;23:794-802.
PUBMED
7. Inglese M, Makani S, Johnson G, Cohen BA, Silver JA, Gonen O, et al. Diffuse axonal injury in mild
traumatic brain injury: a diffusion tensor imaging study. J Neurosurg 2005;103:298-303.
PUBMED | CROSSREF
8. Niogi SN, Mukherjee P, Ghajar J, Johnson C, Kolster RA, Sarkar R, et al. Extent of microstructural white
matter injury in postconcussive syndrome correlates with impaired cognitive reaction time: a 3T diffusion
tensor imaging study of mild traumatic brain injury. AJNR Am J Neuroradiol 2008;29:967-973.
PUBMED | CROSSREF
9. Shenton ME, Hamoda HM, Schneiderman JS, Bouix S, Pasternak O, Rathi Y, et al. A review of magnetic
resonance imaging and diffusion tensor imaging findings in mild traumatic brain injury. Brain Imaging
Behav 2012;6:137-192.
PUBMED | CROSSREF
10. Jang SH, Kim SY. Injury of the corticospinal tract in patients with mild traumatic brain injury: a diffusion
tensor tractography study. J Neurotrauma. Forthcoming 2016.
PUBMED | CROSSREF
11. Yang DS, Kwon HG, Jang SH. Injury of the thalamocingulate tract in the papez circuit in patients with
mild traumatic brain injury. Am J Phys Med Rehabil 2016;95:e34-e38.
PUBMED | CROSSREF
12. Jang SH, Kim TH, Kwon YH, Lee MY, Lee HD. Postural instability in patients with injury of corticoreticular
pathway following mild traumatic brain injury. Am J Phys Med Rehabil. Forthcoming 2016.
PUBMED | CROSSREF
13. 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 (Baltimore) 2016;95:e3007.
PUBMED | CROSSREF
http://e-bnr.org
https://doi.org/10.12786/bn.2016.9.e1
6/8
Diagnostic History of Traumatic Axonal Injury
Brain & NeuroRehabilitation
14. Jang SH, Kwon HG. Injury of the ascending reticular activating system in patients with fatigue
and hypersomnia following mild traumatic brain injury: two case reports. Medicine (Baltimore)
2016;95:e2628.
PUBMED | CROSSREF
15. Aubry M, Cantu R, Dvorak J, Graf-Baumann T, Johnston K, Kelly J, et al. Summary and agreement
statement of the First International Conference on Concussion in Sport, Vienna 2001. Recommendations
for the improvement of safety and health of athletes who may suffer concussive injuries. Br J Sports Med
2002;36:6-10.
PUBMED | CROSSREF
16. Alexander MP. Mild traumatic brain injury: pathophysiology, natural history, and clinical management.
Neurology 1995;45:1253-1260.
PUBMED | CROSSREF
17. Belanger HG, Vanderploeg RD, Curtiss G, Warden DL. Recent neuroimaging techniques in mild
traumatic brain injury. J Neuropsychiatry Clin Neurosci 2007;19:5-20.
PUBMED | CROSSREF
18. Sharp DJ, Jenkins PO. Concussion is confusing us all. Pract Neurol 2015;15:172-186.
PUBMED | CROSSREF
19. Mild Traumatic Brain Injury Committee of the Head Injury Interdisciplinary Special Interest Group of the
American Congress of Rehabilitation Medicine. Definition of mild traumatic brain injury. J Head Trauma
Rehabil 1993;8:86-87.
CROSSREF
20. Carroll LJ, Cassidy JD, Holm L, Kraus J, Coronado VGWHO Collaborating Centre Task Force on Mild
Traumatic Brain Injury. Methodological issues and research recommendations for mild traumatic
brain injury: the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury. J Rehabil Med
2004;36:113-125.
PUBMED | CROSSREF
21. Levin HS, Diaz-Arrastia RR. Diagnosis, prognosis, and clinical management of mild traumatic brain
injury. Lancet Neurol 2015;14:506-517.
PUBMED | CROSSREF
22. Hill CS, Coleman MP, Menon DK. Traumatic axonal injury: mechanisms and translational opportunities.
Trends Neurosci 2016;39:311-324.
PUBMED
23. Maxwell WL, Povlishock JT, Graham DL. A mechanistic analysis of nondisruptive axonal injury: a review. J
Neurotrauma 1997;14:419-440.
PUBMED | CROSSREF
24. Johnson VE, Stewart W, Smith DH. Axonal pathology in traumatic brain injury. Exp Neurol 2013;246:35-43.
PUBMED | CROSSREF
25. Povlishock JT. Traumatically induced axonal injury: pathogenesis and pathobiological implications. Brain
Pathol 1992;2:1-12.
PUBMED
26. Povlishock JT, Christman CW. The pathobiology of traumatically induced axonal injury in animals and
humans: a review of current thoughts. J Neurotrauma 1995;12:555-564.
PUBMED | CROSSREF
27. Parizel PM, Ozsarlak, , Van Goethem JW, van den Hauwe L, Dillen C, Verlooy J, et al. Imaging findings in
diffuse axonal injury after closed head trauma. Eur Radiol 1998;8:960-965.
PUBMED | CROSSREF
28. Büki A, Povlishock JT. All roads lead to disconnection?--Traumatic axonal injury revisited. Acta Neurochir
(Wien) 2006;148:181-193.
PUBMED | CROSSREF
29. McMahon P, Hricik A, Yue JK, Puccio AM, Inoue T, Lingsma HF, et al. Symptomatology and functional
outcome in mild traumatic brain injury: results from the prospective TRACK-TBI study. J Neurotrauma
2014;31:26-33.
PUBMED | CROSSREF
30. Rapp PE, Curley KC. Is a diagnosis of “mild traumatic brain injury” a category mistake? J Trauma Acute
Care Surg 2012;73:S13-S23.
PUBMED | CROSSREF
31. Rutherford WH, Merrett JD, McDonald JR. Symptoms at one year following concussion from minor head
injuries. Injury 1979;10:225-230.
PUBMED | CROSSREF
http://e-bnr.org
https://doi.org/10.12786/bn.2016.9.e1
7/8
Diagnostic History of Traumatic Axonal Injury
Brain & NeuroRehabilitation
32. D’souza MM, Trivedi R, Singh K, Grover H, Choudhury A, Kaur P, et al. Traumatic brain injury and the postconcussion syndrome: a diffusion tensor tractography study. Indian J Radiol Imaging 2015;25:404-414.
PUBMED | CROSSREF
33. Messé A, Caplain S, Paradot G, Garrigue D, Mineo JF, Soto Ares G, et al. Diffusion tensor imaging and
white matter lesions at the subacute stage in mild traumatic brain injury with persistent neurobehavioral
impairment. Hum Brain Mapp 2011;32:999-1011.
PUBMED | CROSSREF
34. Mittl RL, Grossman RI, Hiehle JF, Hurst RW, Kauder DR, Gennarelli TA, et al. Prevalence of MR evidence
of diffuse axonal injury in patients with mild head injury and normal head CT findings. AJNR Am J
Neuroradiol 1994;15:1583-1589.
PUBMED
35. Rand CW, Courville CB. Histologic changes in the brain in cases of fatal injury to the head; alterations in
nerve cells. Arch Neurol Psychiatry 1946;55:79-110.
PUBMED | CROSSREF
36. Adams JH, Graham DI, Murray LS, Scott G. Diffuse axonal injury due to nonmissile head injury in
humans: an analysis of 45 cases. Ann Neurol 1982;12:557-563.
PUBMED | CROSSREF
37. Adams JH, Doyle D, Ford I, Gennarelli TA, Graham DI, McLellan DR. Diffuse axonal injury in head injury:
definition, diagnosis and grading. Histopathology 1989;15:49-59.
PUBMED | CROSSREF
38. Blumbergs PC. Changing concepts of diffuse axonal injury. J Clin Neurosci 1998;5:123-124.
PUBMED | CROSSREF
39. Povlishock JT, Becker DP, Cheng CL, Vaughan GW. Axonal change in minor head injury. J Neuropathol
Exp Neurol 1983;42:225-242.
PUBMED | CROSSREF
40. Saatman KE, Duhaime AC, Bullock R, Maas AI, Valadka A, Manley GTWorkshop Scientific Team and
Advisory Panel Members. Classification of traumatic brain injury for targeted therapies. J Neurotrauma
2008;25:719-738.
PUBMED | CROSSREF
41. Oppenheimer DR. Microscopic lesions in the brain following head injury. J Neurol Neurosurg Psychiatry
1968;31:299-306.
PUBMED | CROSSREF
42. Blumbergs PC, Scott G, Manavis J, Wainwright H, Simpson DA, McLean AJ. Staining of amyloid precursor
protein to study axonal damage in mild head injury. Lancet 1994;344:1055-1056.
PUBMED | CROSSREF
43. Bigler ED. Neuropsychological results and neuropathological findings at autopsy in a case of mild
traumatic brain injury. J Int Neuropsychol Soc 2004;10:794-806.
PUBMED | CROSSREF
44. Mac Donald CL, Dikranian K, Bayly P, Holtzman D, Brody D. Diffusion tensor imaging reliably detects
experimental traumatic axonal injury and indicates approximate time of injury. J Neurosci 2007;27:11869-11876.
PUBMED | CROSSREF
45. Basser PJ, Mattiello J, LeBihan D. MR diffusion tensor spectroscopy and imaging. Biophys J 1994;66:259-267.
PUBMED | CROSSREF
46. Basser PJ, Pajevic S, Pierpaoli C, Duda J, Aldroubi A. In vivo fiber tractography using DT-MRI data. Magn
Reson Med 2000;44:625-632.
PUBMED | CROSSREF
47. Mori S, Crain BJ, Chacko VP, van Zijl PC. Three-dimensional tracking of axonal projections in the brain by
magnetic resonance imaging. Ann Neurol 1999;45:265-269.
PUBMED | CROSSREF
http://e-bnr.org
https://doi.org/10.12786/bn.2016.9.e1
8/8