- Academic Editor
Objectives: Using diffusion tensor tractography (DTT), we demonstrated
the spinothalamic tract (STT) injury in patients with central pain following
whiplash injury. Our primary hypothesis is that fractional anisotropy (FA) and
tract volume (TV) of the STT in injured people differ from non-injured people.
Our secondary hypothesis is that the direction of the collision results in a
different type of injury. Methods: Nineteen central pain patients
following whiplash injury and 19 normal control subjects were recruited. The STT
was reconstructed by the DTT, the FA and TV of the STT were measured. In
addition, different characteristics of the STT injury according to the collision
direction were investigated. Results: The FA value did not differ
significantly between the patient and control groups (p
Whiplash injury is caused by sudden acceleration-deceleration, to the above cervical level such as head and neck [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14]. The patient with whiplash injury suffers varied symptoms, including some suggesting brain injury such as posttraumatic headache, posttraumatic concussion syndrome and posttraumatic chronic pain [2, 3, 4, 5, 6, 7, 8, 9, 10]. Example studies of symptoms indicating brain injury in whiplash injury patients describe changes of perfusion or blood flow in functional neuroimaging studies, increased gray matter density in voxel-based morphometry study and axonal injury in brain dissection study for post-mortem brain [12, 13, 14].
Pain is a common and cardinal symptom in patients with whiplash injury [1, 15]. Although neck pain due to sprain is the most common pain following whiplash injury, a significant portion of patients with whiplash show neuropathic pain: 34% of patients have neuropathic pain component following acute whiplash [1, 16, 17]. Possible mechanisms for neuropathic pain include central hypersensitivity, increased activity in brain areas of pain and additional cortical areas, maladaptive neuroplasticity and cortical reorganization, structural brain change, alterations in neurochemistry, and disruption of the brain default mode network [1, 12, 13, 14, 16, 18, 19, 20].
Since development of diffusion tensor imaging (DTI), a few studies using diffusion tensor tractography (DTT), reported injuries of the corticospinal tract, corticoreticulospinal tract (CRT), dentatorubrothalamic tract (DRTT), ascending reticular activating system (ARAS), auditory radiation (AR), and spinothalamic tract (STT) following whiplash injury [21, 22, 23, 24, 25, 26, 27]. However, all of these studies were case reports, and only one case study reported specifically an injury of the STT [21, 22, 23, 24, 25, 26, 27].
In this study, we demonstrated the STT injury in central pain patients following whiplash injury, using DTT. Our primary hypothesis is that fractional anisotropy (FA) and tract volume (TV) of the STT in injured people differ from non-injured people. Our secondary hypothesis is that the direction of the collision results in a different type of injury.
Nineteen patients (man: 11, women: 8, mean-age: 44.7
|Patient group||Control group||p-value|
|Mean age, year||44.7 (12.6)||41.1 (11.3)||0.75|
|LOC, minutes||1.1 (2.0)||-|
|PTA, minutes||5.0 (13.5)||-|
|GCS score||15.0 (0.0)||-|
|VAS score||5.1 (1.1)||-|
|Mean duration to DTI (months)||9.25 (13.9)||-|
|Location of central pain||Head||18 (94.7%)|
|Arm and Leg||15 (78.9%)|
Values represent mean (
Central pain was selected highest score using Visual Analogue Scale (VAS). The
reliability and validity of the VAS are well-established . The average VAS
score was 6.2
DTI scanning was performed at an average of 9.3
Fiber tracking was performed by FMRIB Software Library (FSL, https://www.fmrib.ox.ac.uk/datasets/techrep/tr04ss2/tr04ss2/node19.html) with the default tractography option . Head motion effect and image distortion due to eddy current were corrected by affine multi-scale two-dimensional registration. For reconstruction of the STT, the regions of interest (ROIs) of the STTs were placed. A seed ROI was placed on the posterolateral medulla on an axial slice . Two target regions of interest were placed on the portion of the ventro-postero-lateral nucleus of the thalamus and primary somatosensory cortex on the axial images . A threshold of two streamlines was applied for the results of fiber tracking. The values of fractional anisotropy (FA) and tract volume (TV) of the STT were measured in both hemispheres.
SPSS software (SPSS for Windows, Version 15.0. SPSS Inc., Chicago, IL, USA) was
used for statistical analysis. An independent t-test was used to compare
FA and TV between the patient and control groups. Regarding the value of FA,
there was no significant differences were observed (p
The result of DTT parameters of the STT between the patient and control groups
is shown in Table 2. The FA value did not differ significantly between the
patient and control groups (p
|Patient group||Control group||p-value|
|DTT Parameters||FA||Right||0.39 (0.06)||0.41 (0.03)||0.41|
|Left||0.41 (0.06)||0.43 (0.04)||0.44|
|TV||Right||908.32 (458.82)||1800.83 (617.34)||0.01|
|Left||982.42 (651.59)||1896.28 (795.27)||0.01|
Values represent mean (
In this study, the patient with frontal or rear-end car collision was
registered. The onset of central pain was significantly delayed (13.5 days) in
patients who were involved in a frontal collision, compared to patients in a
rear-end collision (0.6 days) (p
|Frontal collision||Rear-end collision||p-value|
|Duration to pain onset (days)||13.5||0.6||0.01|
|Primary injury||0/6 (0%)||7/13 (53.8%)|
|Secondary injury||6/6 (100%)||6/13 (46.2%)|
VAS, visual analogue scale.
In this study, we demonstrated the STT injury using DTT parameters in patients with central pain following whiplash injury and found the following results (Fig. 1, Tables 1,2,3). First, TV of the STT in the patient group was lower than the control group; however, FA value did not differ. Second, patients in a frontal collision (13.5 days) showed delayed onset of central pain more than the patients in a rear-end collision (0.6 days). All patients in a frontal collision suffered secondary axonal injury, but approximately half of patients in a rear-end collision did.
Examples of injury of the spinothalamic tract on diffusion tensor tractography.
Result of DTT parameters, FA and TV are most commonly used to evaluate the condition of a neural tract with brain injury. FA value indicates water diffusion directionality degree, and the white matter organization . In detail, it indicates the degree of directionality of white matter microstructures such as axon, myelin, and microtubule . TV indicates the included number of voxels in a neural tract, suggests fiber numbers of a neural tract . Therefore, the decrease of TV without change of FA value in the patient group appeared to indicate injury of the STT. Because the conventional brain MRI, electromyography, and nerve conduction studies in the patient group were normal, traumatic axonal injury (TAI) was the most likely pathogenic mechanism for injuries of the STT [37, 38, 39, 40].
The primary axonal injury indicates that the axons are damaged by shear or strain injury at the time of injury that lead to disconnection or malfunction of neuron’s interconnection . In contrast, the secondary axonal injury refers to a condition in which axons were not damaged at the time of injury (evolve over a period of time from hours to days after the primary brain injury), but undergo axonal injury caused by the sequential process of cellular, chemical, or tissue such as decreased axoplasmic transport, continued axonal swelling, and subsequent ~ ultimate disconnection that lead to increased mortality [38, 41]. Central pain onset was delayed in the patients in a frontal collision (13.5 days) compared with patients in a rear-end collision (0.6 days). Considering the definition of the primary and secondary axonal injury, the patients in a frontal collision had secondary injuries (the onset duration of the central pain was more than four hours after whiplash injury) much more than the patients in a rear-end collision. In detail, usually, we could not take a defensive physical position when the accident occurs rear-end collision and it may result the direct injury (primary injury). However, when the accident occurs frontal collision, the occupant could take a defensive physical position. Although it prevents direct injury (primary injury), but due to the acceleration-deceleration force, the brain shaking is unavoidable. We assume that this may results secondary injury. Therefore, these results suggest that TAIs in the patients in a frontal collision were mainly attributed to the secondary injury than the patients in a rear-end collision [38, 41].
We think that the higher risk of secondary injury in the patients in a frontal collision might be related to time to protect their body when colliding in front rather than the rear.
TAI is demonstrably associated with whiplash injury [19, 20, 21, 22, 23, 24]. Before introduction of DTI, a few studies reported on TAI following whiplash injury in the post-mortem brain dissection study [19, 20]. In 1982, Gennarelli et al.  applied artificial whiplash force to 45 monkeys, and 26 of 45 monkeys suffered brain injury, with 18 of those 26 monkeys revealed to have diffuse axonal injury on post-mortem brain dissection. In 1998, Shannon et al.  reported that axonal injury was detected on post-mortem brain dissection in 14 children with shaken baby syndrome. After introduction of DTI, several studies using DTT demonstrated TAI following whiplash injury in patients with mild TBI [21, 22, 23, 24, 25, 26, 27]. In 2019, Jang and Seo reported on two patient with mild TBI who showed injury of STT with central pain following whiplash injury . From 2015 to 2019, Jang et al. [21, 22, 23, 24, 25, 26, 27] reported several manuscripts of TAI using DTT in the patient (suffering tremor, ataxia, hypersomnia, impaired motor function, tinnitus and neural pain) with neural tract injury such as DRTT, ARAS, Corticospinal tract (CST), CRT, AR and STT after whiplash injury. Therefore, to the best of our knowledge, this is the first original study to demonstrate the STT injury in large number of patients after whiplash injury.
However, some limitation of this study should be considered. First, this study included a small number of subjects. In addition, we recruited patients who visited the rehabilitation department of a university hospital, therefore, it is possible that severe clinical manifestation mild TBI patients would be recruited. Second, although DTT is a powerful anatomic imaging technique that can demonstrate gross fiber architecture, it can produce both false positive and negative results due to crossing fiber or partial volume effect [42, 43].
In this study, we found injury of the STT in patients with mild TBI who suffered central pain after whiplash injury, using DTT. In addition, we demonstrated different characteristics of the STT injury according to the collision direction. We believe that DTT would be a useful technique for detection of injury of the STT following whiplash injury and can be recommended for patients who complain of brain symptoms after whiplash injury.
All data generated or analysed during this study are included in this published article.
SHJ—Project administration, Writing – original draft. KK—Data curation, Methodology. YSS—Formal analysis, Methodology, Writing – review & editing.
All subjects gave their informed consent for inclusion before they participated in the study. The protocol was approved by the Yeungnam University Hospital Institutional Review Board (approval number: YUMC 2021-03-014).
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean Government (MSIP) (No. 2022R1F1A1073458). This work was supported by the Korea Medical Device Development Fund grant funded by the Korea government (the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, the Ministry of Health & Welfare, the Ministry of Food and Drug Safety) (Project Number: KMDF_PR_20200901_0199).
The authors declare no conflict of interest.
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