- Academic Editor
Background: The cerebellum is connected to the brain stem by three
pairs of cerebellar peduncles (CPs)—superior (SCP), middle (MCP), and inferior
(ICP)—which carry proprioceptive information to regulate movement and maintain
balance and posture. Injury or damage to the CPs caused by tumors, infarcts, or
traumatic brain injuries (TBI) results in poor coordination and balance problems.
Current data on CP-related injuries and their effect on balance control are
sparse and restricted to a few case studies. There have been no studies to date
that have investigated CP injuries in a large sample of patients with balance
problems following a mild TBI. Hence, we investigated CP-related injuries in
patients with balance problems following mild TBI using diffusion tensor
tractography (DTT). Methods: Twenty-one patients with TBI and 21 normal
subjects were recruited for this study. Balance was evaluated using the Balance
Error Scoring System (BESS). Three DTT-related parameters—fractional anisotropy
(FA), apparent diffusion coefficient (ADC), and fiber number (FN) of the
CPs—were measured. Results: The FN values of the SCP and ICP in the
patient group were significantly lower than those in the control group (p
The cerebellum plays a crucial role in the regulation of movement and maintenance of balance and posture. In addition to its well-defined role in motor coordination, there is increasing evidence that the cerebellum contributes to several cognitive features and emotional control [1, 2, 3]. The three cerebellar peduncles (CPs), which connect the cerebellum to the brain stem and cerebrum, are involved in motor control and carry somatosensory information, such as that involved with proprioception (the body’s ability to sense movement, action, and location), and vestibular information (the sense of balance and information about body position) [1, 2, 3]. The superior cerebellar peduncles (SCPs) are paired (afferent and efferent) tracts that connect the cerebellum to the mid-brain containing the red nucleus and the ventrolateral thalamus involved in motor control and continue to the cerebral cortex via the thalamocortical pathway [4]. They carry vestibular information and proprioceptive inputs for motor control [4]. The middle cerebellar peduncle (MCP) contains only the afferent tract connecting the pontine nucleus to the cerebellum and is associated with higher cognitive and motor-sensory functions, thereby modulating skilled movements [4]. The inferior cerebellar peduncle (ICP) has four afferent tracts and one efferent tract connecting the spinal cord to the cerebellum [4]. It integrates somatosensory information, including the proprioceptive and motor vestibular inputs for balance and posture maintenance [4], for motor control, such as motor coordination, balance control, and gait, and other types of skilled movements [1, 2, 3, 4, 5]. Injuries to the CPs caused by tumors, infarcts, and traumatic brain injury (TBI) can result in loss of motor control [5, 6, 7, 8, 9, 10, 11, 12, 13, 14].
Traumatic brain injury is a broad term that describes a vast array of injuries from focal to diffuse and is a major cause of functional disabilities such as motor weakness, imbalance [15, 16]. Studies have reported that TBIs to the medial lemniscus and cerebellum are associated with poor balance [17, 18, 19, 20, 21, 22]. Caeyenberghs et al. (2012) [19] demonstrated that lower connectivity between the cerebellum and parietal gyrus was significantly correlated with poor balance in young patients with traumatic axonal injury (TAI). In terms of severity, TBI is classified into three types: mild, moderate, and severe [23]. Mild TBI accounts for 70–85% of all TBIs [23, 24]. While loss of balance and stability is a common physical symptom following mild TBI, it is difficult to detect the lesion using conventional brain computed tomography (CT) and magnetic resonance imaging (MRI) [25, 26]. However, diffusion tensor imaging (DTI) makes it possible to probe microscopic or small injuries that are invisible in two-dimensional images by measuring the directional coherence of water diffusion in white matter [27]. Furthermore, diffusion tensor tractography (DTT), derived from DTI, has the advantage of using three dimensions to visualize and evaluate specific neural tracts by measuring the quantitative indices of fractional anisotropy (FA), apparent diffusion coefficient (ADC), and fiber number (FN) [28, 29]. Thus, many studies have used DTT to evaluate neural tract injuries following mild TBI [30, 31, 32]. Specifically, injuries to several neural tracts, including the corticobulbar tract, fornix, and spinothalamic tract following mild TBI, have been reported using DTT [30, 31, 32]. However, there is very little data on CP-related injuries in mild TBI, barring one case study on an injury to the ICP [13]. To date, no study has investigated a large sample of patients with balance problems following a mild TBI for injuries to the three CPs. This study hypothesized that injury to CPs and mild TBI could be the cause of balance problems in these patients.
Thus, we used DTT to investigate injuries to the three CPs in patients with balance problems following mild TBI.
We recruited twenty-one patients (male: 10, female: 11, mean age: 42.4
Patient group | Control group | p-value | |
Sex (male:female) | 10:11 | 10:11 | 1.000 |
Mean age, years | 42.4 (9.6) | 40.5 (9.2) | 0.373 |
LOC, minutes | 5.14 (6.97) | ||
PTA, minutes | 14.62 (21.67) | ||
GCS score | 14.86 (0.48) | ||
Mean duration to DTI, months | 5.4 (3.9) | ||
BESS score | 20.7 (5.8) | 10.6 (4.3) | 0.000 |
Values represent mean (
Balance was evaluated using the Balance Error Scoring System (BESS), a reliable
and valid tool for assessing postural stability [33]. Three different stances
(double-leg [hands on the hips and feet together], one-leg [standing on the
non-dominant leg with hands on hips], and tandem stances [non-dominant foot
behind the dominant foot]) were tested twice, once on a firm surface and once on
balance foam for a total of six trials. The order of the clinical tests was
randomized between subjects and sessions, with each test lasting 20 seconds.
Subjects were instructed to maintain balance, make any necessary adjustments, and
return to the testing position as quickly as possible. Performance was scored by
the addition of 1 error point for each error committed, and the range of scores
was 0–60 (lower scores indicate better balance and fewer errors). The average
BESS score in the patient group (20.7
Diffusion tension imaging data were acquired 5.4
SPSS software (SPSS for Windows, Version 15.0; SPSS Inc., Chicago, IL, USA) was
used for the statistical analysis. Levene’s Test for equality of variances was
used to assess the meeting of the statistical assumption of homogeneity of
variance between the patient and control groups, and equal variance was met. An
independent t-test was used to compare the BESS score and DTT parameters
(FA, ADC, and FN values) between the patient and control groups. The null
hypothesis of no difference was rejected if the p-values were less than 0.05. The
statistical power of the sample size was calculated using G*Power 3.1 (Version
9.4, Heinrich Heine University Düsseldorf, Düsseldorf, North
Rhine-Westphalia, Germany) and showed a 0.5 effect size, 0.05
Thinning of both SCPs and discontinuation of both ICPs were observed in the
patient group when compared with the control group (Fig. 1). A summary of the
results of the CP-related DTI parameters measured in the patient and control
groups is shown in Table 2. The FN values of the SCP and ICP in the patient group
were significantly lower than the values in the control group (p
Results of brain magnetic resonance (MR) images and diffusion tensor tractography of the three cerebellar peduncles. (A) T2-weighted brain MR images show no abnormalities in a patient and a control. (B) Results of diffusion tensor tractography of the three cerebellar peduncles in a patient and a control. Compared with the control, thinning (purple arrows) of both superior cerebellar peduncles and discontinuation (sky-blue arrows) of both inferior cerebellar peduncles are seen in the patient.
Patient group | Control group | ||||||
FA | ADC | FN | FA | ADC | FN | ||
SCP | Right | 0.48 (0.03) | 0.84 (0.06) | 1086.38 (574.94) | 0.48 (0.02) | 0.82 (0.03) | 1456.41 (519.43) |
Left | 0.49 (0.03) | 0.81 (0.04) | 1121.10 (620.93) | 0.50 (0.03) | 0.80 (0.03) | 1603.36 (546.23) | |
Both | 0.49 (0.03) | 0.82 (0.05) | 1103.74 |
0.49 (0.03) | 0.81 (0.03) | 1529.89 (531.98) | |
MCP | Right | 0.51 (0.02) | 0.79 (0.03) | 4879.43 (1243.08) | 0.51 (0.01) | 0.80 (0.03) | 4606.55 (1193.04) |
Left | 0.51 (0.02) | 0.80 (0.03) | 4902.76 (1105.38) | 0.52 (0.01) | 0.80 (0.03) | 4774.23 (922.01) | |
Both | 0.51 (0.02) | 0.79 (0.03) | 4891.10 (1161.87) | 0.51 (0.01) | 0.80 (0.03) | 4690.39 (1057.11) | |
ICP | Right | 0.48 (0.03) | 0.84 (0.04) | 279.57 (83.13) | 0.48 (0.02) | 0.85 (0.03) | 326.32 (64.39) |
Left | 0.48 (0.03) | 0.86 (0.06) | 239.29 (102.18) | 0.47 (0.03) | 0.86 (0.03) | 319.59 (76.36) | |
Both | 0.48 (0.03) | 0.85 (0.05) | 259.43 |
0.48 (0.03) | 0.85 (0.03) | 322.95 (69.89) |
Values represent mean (
In the current study, injuries to the three CPs were investigated using DTT in patients with balance problems following mild TBI. The patient group showed injuries to the SCP and ICP (as observed by a decrease in the FN value) compared with the control group. However, based on the FN values, the MCPs in the patient group did not appear to be injured. This could be attributed to the more robust anatomical characteristics of the MCP, with large or thick fibers relative to the SCP and ICP [4]. In addition, the junction areas between the brain stem and the cerebellum involving the SCP and ICP are probably the most vulnerable to injuries [6]. Among the commonly assessed DTT parameters, the FA, ADC, and FN have been widely used to detect injuries of the neural tracts [27, 37]. The FA value measures the directionality of diffusion and reflects fiber density and axonal diameter, ranging from 0 to 1 [37]. The ADC value is an index of the rate of diffusion averaged over all directions [37]. The FN value indicates the volume of the neural tract based on the number of voxels within the neural tract [37]. Thus, a decrease in the FA or FN or an increase in the ADC represents injuries of the neural tract [27, 37]. As the patients did not show any specific lesions on conventional MRIs, we believe the decrease in the FN of the SCP and ICP in the patient group could be at least partly ascribed to balance problems.
Several DTI-based studies have reported damage to CPs in patients with brain injuries caused by tumors, multiple sclerosis, and infarcts [5, 6, 7, 8]. Hong et al. (2009) [6] investigated the CPs in six patients with gait and balance problems and found injuries to the SCP and ICP at the junction area between the brain stem and cerebellum following a diffuse axonal injury. In 2015, Drijkoningen et al. [7] demonstrated that improvements in balance were associated with recovery of the injured ICP in 19 patients with moderate to severe TBI. In 2020, Gera et al. [5] reported that SCP and ICP injuries were related to posture sway in 29 patients with multiple sclerosis. They asserted that the SCP contributed to the control of the standing posture with visual information, and that the ICP contributed to the control of standing balance regardless of visual information. Kim et al. (2021) [8] demonstrated that an injured ICP showed a moderate correlation with gait function in 27 patients with hemorrhagic stroke. All the studies indicated that injuries to the SCP and ICP were associated with balance or gait problems in patients with brain injuries. The results of our study agree with the results of these earlier studies.
Few DTT-based studies have reported CP injury in patients with balance problems [9, 10, 11, 12, 13, 14]. Yamada et al. (2003) [9] demonstrated that the forward-leaning posture and inability to walk in a patient with a lateral medullary infarct were ascribed to an injury of the ICP. In 2010, Hong and Jang described injuries to the three CPs that were involved with poor balance in six patients with cerebellar infarcts [10]. Kwon and Jang (2012) [11] found injuries of various neural tracts, including the corticospinal tract, fornix, and ICP, in a patient with gait disturbance following a diffuse axonal injury. Subsequently, Kim et al. (2014) [12] found that an injured SCP affected the gait and balance in a patient with a tumor. They also reported that the recovery of the SCP mainly contributed to an improvement of the balance and gait function after 3 months. In 2019, Kim et al. [14] demonstrated that decreased axial diffusivity in the left ICP positively correlated with poor balance control in 15 patients with mild to moderate TBI. One case study in three patients with mild TBI investigated the injury to the ICP and demonstrated that the gait and balance problems could be ascribed to a decrease in the FN of the ICP [13]. In all these studies, injuries to the SCP and ICP were related to balance problems, as was seen in our study. In addition, because the functions of the SCP and ICP are to carry and integrate vestibular and proprioception information, the balance problems in our patients appeared to be ascribed to injuries to the SCP and ICP. To the best of our knowledge, this is the first study to demonstrate injuries to both the SCP and ICP using DTT in a large number of patients with mild TBI. However, some limitations of this study should be considered [38, 39]. First, we recruited patients who had been admitted for rehabilitation at a university hospital. Therefore, it is possible that among all the patients with mild TBI, we only recruited chronic patients with severe clinical manifestations. Second, the fiber tracking technique is operator dependent. Third, DTT could lead to both false-positive and false-negative results throughout the white matter of the brain because of complex fiber configurations such as crossing or kissing fiber and partial volume effects.
Using DTT, we demonstrated that the balance problems in patients with mild TBI could be attributed to injuries to the SCP and ICP. Our results suggest that DTT could be useful in detecting injuries to CPs that may not be detected on conventional brain MRI in patients with mild TBI.
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
SHJ: study concept and design, manuscript development, writing, and critical revision of the manuscript for intellectual content. HGK: study concept, funding, design, data analysis, and critical revision of the manuscript for intellectual content. Both authors contributed to editorial changes in the manuscript. Both authors read and approved the final manuscript. Both authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.
The patients and control subjects provided signed, informed consent, and the study protocol was approved by Yeungnam University Hospital institutional review board (approval number: YUMC 2021-03-014).
Not applicable.
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2022R1F1A1066512).
The authors declare no conflict of interest.
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