http://informahealthcare.com/bij ISSN: 0269-9052 (print), 1362-301X (electronic) Brain Inj, 2015; 29(1): 110–114 ! 2015 Informa UK Ltd. DOI: 10.3109/02699052.2014.973447

CASE STUDY

Traumatic axonal injury of the corticospinal tract in the subcortical white matter in patients with mild traumatic brain injury Jeong Pyo Seo & Sung Ho Jang

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Department of Physical Medicine and Rehabilitation, College of Medicine, Yeungnam University, Taegu, Republic of Korea

Abstract

Keywords

Background: Little is known about injury of the corticospinal tract (CST) in patients with mild traumatic brain injury (TBI). This study reports on patients with mild TBI who showed traumatic axonal injury of the CST in the sub-cortical white matter, as demonstrated by diffusion tensor tractography (DTT). Methods: Four patients with mild TBI who complained of motor weakness and had DTT parameters within the normal range, including fractional anisotropy, apparent diffusion coefficient and fibre number of the CST, and 10 normal control subjects were recruited for this study. Results: All four patients showed partial tearing of the CSTs in a portion of the sub-cortical white matter in both hemispheres on DTT. However, three patients showed low amplitude on motor evoked potential obtained from both hand muscles by transcranial magnetic stimulation and two patients revealed abnormality of hand motor function in terms of grip strength or Purdue Pegboard score. Conclusions: This study demonstrated traumatic axonal injury of the CST using configurational evaluation of DTT in patients with mild TBI. It is believed that configurational evaluation using DTT would be a useful technique for detection of localized traumatic axonal injury in patients with mild TBI.

Axonal injury, corticospinal tract, diffusion tensor imaging, mild traumatic brain injury

Introduction Traumatic brain injury (TBI) is a major cause of mortality and disability. Motor weakness is one of the main sequelae, along with cognitive dysfunction and behaviour problems in patients with TBI [1, 2]. Incidence of motor weakness following TBI of 9–56% has been reported [1, 2]. The corticospinal tract (CST) is an important neural tract for motor function in the human brain, particularly fine motor activities of the hand [3, 4]. Recently-developed diffusion tensor imaging (DTI) enables estimation of the CST in terms of quantitative evaluation using DTI parameters and configurational evaluation using diffusion tensor tractography (DTT) in the live human brain [5]. As a result, many studies have demonstrated injury of the CST in patients with TBI, using these two methods for evaluation using DTI [6–10]. Regarding mild TBI, although a few studies have reported injury of the CST using quantitative evaluation of DTI parameters, diagnosis of injury of the CST could be difficult if the values of DTI parameters are within normal

Correspondence: Sung Ho Jang, MD, Department of Physical Medicine and Rehabilitation, College of Medicine, Yeungnam University 317-1, Daemyungdong, Namku, Taegu, 705-717, Republic of Korea. Tel: 82-53-620-3269. Fax: 82-53-620-3269. E-mail: strokerehab@ hanmail.net

History Received 1 January 2014 Revised 4 August 2014 Accepted 2 October 2014 Published online 30 October 2014

range because injury of the CST is localized to certain areas [11–13]. Therefore, it was hypothesized that configurational evaluation using DTT would be helpful in demonstration of a mild localized injury of the CST in patients with mild TBI The current study reports on patients with mild TBI who showed axonal injury of the CST in the sub-cortical white matter, as demonstrated by DTT.

Patients and methods Subjects Four patients and 10 normal control subjects (six males, four females; mean age ¼ 38.6 years, range ¼ 35–44) with no history of neurologic or psychiatric disease were recruited for this study. Patients were enrolled according to the following inclusion criteria: (1) loss of consciousness (LOC) for 30 minutes or less, post-traumatic amnesia (PTA) for less than 24 hours and Glasgow Coma Scale (GCS) score of 13–15 recorded 30 minutes post-injury or later upon presentation for healthcare [14], (2) DTT parameters for both CSTs in terms of FA, ADC and fibre number were within normal range (Table I), (3) no visible lesion on T1-weighted, T2-weighted, Fluid attenuated inversion recovery (FLAIR) and T2-weighted gradient recall echo (GRE) images and an electromyography study showing no evidence of peripheral nerve injury or radiculopathy and (4) no history of previous

Traumatic axonal injury of the CST in mild TBI

DOI: 10.3109/02699052.2014.973447

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Table I. Diffusion tensor tractography parameters of patients and normal control subjects.

FA Rt Lt ADC Rt Lt Fibre number Rt Lt

Patient 1

Patient 2

Patient 3

Patient 4

Controls (range of 2SD)

0.514 0.531

0.530 0.513

0.499 0.515

0.497 0.495

0.529 (0.483  0.574)

0.903 0.813

0.810 0.797

0.835 0.850

0.804 0.840

0.840 (0.773  0.906)

1125 1509

1632 1505

1390 1098

1523 1240

1577 (1094  2061)

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Control data are presented as mean (±standard deviation); SD, standard deviation; FA, fractional anisotropy; ADC, apparent diffusion coefficient.

head trauma. All subjects provided signed, informed consent and the Institutional Review Board approved the study protocol. Patient 1 was a 39-year-old right-handed male who had suffered head trauma resulting from a car accident. While driving his sedan, his car collided with a truck; consequently, he suffered an acceleration–deceleration injury during flexion– extension of his head. The patient did not show LOC or PTA at the time of head trauma and his GCS was 15 when he arrived at the hospital. He complained of mild weakness of all four extremities and impairment of fine motor activities of both hands. At the time of DTI scanning (15 months after onset), the grip strength of both hands was within the normal range (28/ 21 Kg, normal range ¼ 31.2 ± 8.7/29.8 ± 6.9); however, the fine motor function of both hands had deteriorated to such an extent that the Purdue Pegboard score was 12/11 (normal range ¼ 15.9 ± 1.4/15.4 ± 1.7) [15]. Patient 2 was a 35-year-old female who had suffered head trauma resulting from a car accident. While driving, her car collided with a guard rail in order to avoid an oncoming car. As a result, her head hit the steering wheel and was then moved to the right side and then hit the left car window. The patient experienced LOC for 3 seconds without PTA. Her GCS score was 15 when she arrived at the hospital. At the time of DTI scanning (1 month after onset), the fine motor function of both hands was impaired to such an extent as 10/12 (normal range ¼ 16.4 ± 1.4/16.1 ± 1.2) on the Purdue Pegboard score, although the grip strength of both hands was within the normal range (16/20 Kg, normal range ¼ 13.1 ± 4.7/12.2 ± 4.3) [15]. Patient 3 was a 52-year-old right-handed female who had suffered head trauma resulting from a car accident: while riding her bicycle, she collided with a car. The patient experienced LOC for 10 minutes and PTA for 15 minutes at the time of head trauma and her GCS was 15 when she arrived at the hospital. At the time of DTI scanning (6 weeks after onset), the grip strength of both hands (6/4 Kg, normal range ¼ 15.2 ± 4.3/11.9 ± 4.5) and the fine motor function of both hands on the Purdue Pegboard score (12/8, normal range ¼ 15.6 ± 2.2/14.1 ± 1.8) had deteriorated [15]. Patient 4 was a 30-year-old male who had suffered head trauma resulting from a car accident: while he was sitting in a stopped sedan, the sedan was struck from behind by a bus. As a result, his head hit the steering wheel and was then hyper-extended backward. The patient did not show LOC or PTA at the time of head trauma and his GCS was 15

when he arrived at the hospital. At the time of DTI scanning (12 months after onset), he complained of mild weakness of both hands; however, the grip strength of both hands (48/45 Kg, normal range ¼ 31.2 ± 8.7/29.8 ± 6.9) and the fine motor function of both hands on the Purdue Pegboard score (17/16, normal range ¼ 15.9 ± 1.4/15.4 ± 1.7) were within normal range [15]. Diffusion tensor imaging A synergy-L Sensitivity Encoding (SENSE) head coil on a 1.5 T Philips Gyroscan Intera (Hoffman-La Roche, Best, Netherlands) with single-shot echo-planar imaging and a navigator echo was used for acquisition of DTI data. For each of the 32 non-collinear diffusion sensitizing gradients, 65 contiguous slices were acquired parallel to the anterior commissure–posterior commissure line. Imaging parameters were as follows: matrix ¼ acquisition matrix ¼ 96  96; reconstructed to matrix ¼ 192  192 matrix; field of view ¼ 240 mm  240 mm; TR ¼ 10 398 ms; TE ¼ 72 ms; parallel imaging reduction factor (SENSE factor) ¼ 2; EPI factor ¼ 59; b ¼ 1000 s mm2; NEX ¼ 1; slice gap ¼ 0 mm; and a slice thickness of 2.5 mm. Fibre tracking was performed using the fibre assignment continuous tracking (FACT) algorithm implemented within the DTI task card software (Philips Extended MR WorkSpace 2.6.3). Each of the DTI replications was intra-registered to the baseline ‘b0’ images in order to correct for residual eddy-current image distortions and head motion effect, using a diffusion registration package (Philips Medical Systems, Netherland) (threshold fractional anisotropy ¼ 0.15, angle ¼ 27). For reconstruction of the CST, the first ROI was placed on the anterior blue portion of the upper pons on the axial image of the colour map and the second ROI was placed on the anterior blue portion of the lower pons on the axial image of the colour map [16]. This study measured the value of fractional anisotropy (FA), apparent diffusion coefficient (ADC) and fibre number of the CST. DTI parameter values showing a deviation of more than 2 SD from normal control values were defined as abnormal. Transcranial magnetic stimulation Transcranial magnetic stimulation (TMS) was performed using a Magstim Novametrix 200 magnetic stimulator with a 9 cm mean diameter circular coil (Novametrix Medical Systems Inc, Wallingford, CT, USA). Cortical stimulation was performed with the coil held tangentially over the vertex. The circular coil

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was positioned flat on the scalp with its centre over Cz (international 10/20 system). A counterclockwise current provided stimulation to the left hemisphere and the right hemisphere was stimulated by a clockwise current. Motor evoked potentials (MEPs) were obtained from both abductor pollicis brevis (APB) muscles in a relaxed state. Magnetic stimulation was applied at 100% of maximal output. Each site was stimulated three times with an interval of at least 10 seconds between stimulation. The shortest latencies and average peak-to-peak amplitudes were calculated from the data obtained.

Results

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Patient 1 On 15-month DTT, partial tearing of the CSTs was observed in the middle portion at the sub-cortical white matter in both hemispheres (Figure 1). The MEPs evoked from both APB muscles showed normal latencies and low amplitudes (latencies: 19.7/19.1 milliseconds [normal value ¼ 21.00 ± 0.39 milliseconds], amplitudes: 500/2700 mV [normal value ¼ 4300 ± 400 mV]) [17]. Patient 2 On 1-month DTT, partial tearing of the right CST was observed in the anterior portion at the sub-cortical white matter; in contrast, the left CST showed partial tearing in the middle portion at the sub-cortical white matter. In addition, transcallosal fibres from the right CST were observed (Figure 1). Although the latencies of MEPs evoked from both APB muscles were within normal range, the amplitudes were low (latencies ¼ 17.3/18.5 milliseconds [normal value ¼ 21.00 ± 0.39], amplitudes ¼ 2600/1400 mV [normal value ¼ 4300 ± 400 mV]) [17]. Patient 3 Partial tearing of both CSTs was observed in the middle (right) and posterior (left) portions at the sub-cortical white matter on 6-week DTT (Figure 1). The latencies and amplitudes of MEPs evoked from both APB muscles were within normal range (latencies ¼ 22.1/22.1 milliseconds [normal value ¼ 21.00 ± 0.39], amplitudes ¼ 5500/5100 mV [normal value ¼ 4300 ± 400 mV]) [17]. Patient 4 On 12-month DTT, partial tearing of both CSTs was observed in the posterior (right) and middle (left) portions at the subcortical white matter (Figure 1). However, the latencies and amplitudes of MEPs evoked from both APB muscles were within normal range (latencies ¼ 22.1/22.1 milliseconds [normal value ¼ 21.00 ± 0.39], amplitudes ¼ 5500/5100 mV [normal value ¼ 4300 ± 400 mV]) [17].

Discussion This study attempted to demonstrate injury of the CST in patients with mild TBI. Patients were recruited who corresponded to the criteria of mild TBI in terms of LOC, PTA and GCS and complained of motor weakness since the onset of

Brain Inj, 2015; 29(1): 110–114

head trauma. In addition, patients were enrolled who showed no abnormalities in the DTT parameters of the CST, including FA, ADC and fibre numbers. FA value represents the degree of directionality of microstructures (e.g. axons, myelin and microtubules) and ADC value indicates the magnitude of water diffusion [5]. In contrast, partial tearing of the CST in the subcortical white matter was observed in both hemispheres of these patients. The sub-cortical white matter is known to be a vulnerable area of diffuse axonal injury [10, 18–20]. It is believed that injury of the CST in these patients corresponded to the traumatic axonal injury because the conventional brain MRI of these patients showed no abnormality [21, 22]. Therefore, the results indicate that traumatic axonal injury of the CST could be demonstrated using configurational evaluation of DTT, even though the injured CST showed normal findings in quantitative evaluation using DTT parameters. However, two patients (patients 1 and 2) showed low amplitude of MEP obtained from the hand muscles, indicating low fibre numbers of the CST; in contrast, the two remaining patients (patients 3 and 4) did not show any abnormality on MEP [17]. In addition, one patient (patient 4) did not show abnormality in terms of grip strength or fine motor function of the hand, although he complained of motor weakness after the onset of head trauma. It is believed that two possibilities should be considered for these disparities in the results of clinical evaluation and MEP with DTT findings. First, partial tearing of the CST may not result in abnormalities on clinical evaluation and MEP because partial tearing of the CST is a mild injury and the rest of the CST can work for normal motor function and MEP. Second, patients with an injured CST can gain functional recovery, although the injured CST did not show structural recovery on the configuration. In particular, patient 4, who showed normal clinical finding, was evaluated at 12 months after onset, which seems to be enough time for functional recovery. To confirm this possibility, further follow-up studies from the acute stage to chronic stage should be encouraged. Since the introduction of DTI, many studies have reported on injury of the CST in patients with TBI [6–13, 23, 24]. Among these, only a few studies have reported injury of the CST in patients with mild TBI [11–13]. In 2007, Kraus et al. [11] investigated white matter integrity using ROI analysis in chronic patients with TBI and found that the FA value of the CST was decreased in 20 patients with mild TBI. In 2010, using individual and group analysis, Singh et al. [12] demonstrated injury of the CST in 12 patients with mild-tomoderate TBI (LOC 51 hour). In a recent study, Kasahara et al. [13] demonstrated increased axial diffusivity of the right CST in 10 patients with mild TBI. However, no study has reported configurational evidence of injury of the CST in patients with mild TBI. In conclusion, this study demonstrated axonal injury of the CST using configurational evaluation of DTT in patients with mild TBI. To the best of the authors’ knowledge, this is the first study to provide a visual demonstration of axonal injury of the CST, using DTT in patients with mild TBI. It is believed that configurational evaluation using DTT would be a useful technique for detection of localized traumatic axonal injury in patients with mild TBI. Therefore, DTI scanning can be recommended for patients with mild TBI who complain of

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DOI: 10.3109/02699052.2014.973447

Figure 1. (A) Brain MRIs showed no definite lesions. (B) Results of diffusion tensor tractography of the patients. Both corticospinal tracts showed partial tearing (arrows) in the subcortical white matter. (C) Results of diffusion tensor tractography of normal subjects (control 1: 37 year-old male, control 2: 38 year-old male, control 3: 35 year-old female, control 4: 44 year-old female).

motor weakness. Conduct of further complementary studies involving larger numbers of cases is warranted. Limitations of DTI should be considered; in particular, regions of fibre complexity and crossing can prevent full reflection of the underlying fibre architecture by DTT [25, 26].

Declaration of interest This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2012R1A1A4A01001873).

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Traumatic axonal injury of the corticospinal tract in the subcortical white matter in patients with mild traumatic brain injury.

Little is known about injury of the corticospinal tract (CST) in patients with mild traumatic brain injury (TBI). This study reports on patients with ...
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