Relationship between reticulospinal system sensitization and proprioceptive pathways in the development of dynamic spasticity (ReProDS) post-spinal cord injury: protocol for a prospective, observational cohort study

Abstract

Background

Dynamic spasticity (DS) is a common complication post-spinal cord injury (SCI), marked by intermittent increases in muscle tone during postural transitions or movement. Despite its prevalence, high-quality research on DS incidence, risk factors, and underlying mechanisms in SCI patients remains limited. With the growing application of spinal cord stimulation (SCS) for spasticity control, the role of proprioception in DS development has garnered attention. Additionally, advances in diffusion tensor imaging (DTI) allow for the analysis of the reticulospinal tract’s (RST) role in postural control among SCI patients. However, the impact of microstructural changes in RST and proprioception on DS following SCI remains unclear.

Objective

To investigate the relationship between microstructural changes in the RST and proprioceptive circuits in SCI patients, exploring their association with DS and potential predictive factors that influence recovery.

Methods

This is a 12-month prospective cohort study. The neurophysiological and global functional status of the participants will be assessed. Primary outcomes include DTI indices of RST and proprioception, and spasticity assessment. Secondary outcomes include auditory startle reflex (ASR), H-reflex, shear wave velocity (SWV), overall functional status including spinal cord independence measure, gait analysis, modified Barthel Index, and the 36-item short form health survey. Data will be collected at 1, 3, 6, and 12 months after enrolment. Matched healthy controls will be measured during the same period after recruitment.

Discussion

This study is the first to explore the role of microstructural changes in the RST and proprioception in the assessment and prediction of DS following SCI. The findings aim to enhance theoretical understanding of SCS in spasticity management and to establish pre-treatment criteria for SCS interventions targeting motor function recovery in SCI.

Trial registration number

ChiCTR2400090724.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12883-024-03947-y.

Introduction

Dynamic spasticity (DS) represents a significant complication of spinal cord injury (SCI) [1]. DS is typified by the presence of normal or mildly increased muscle tone at rest, which can precipitously increase during postural transitions (e.g., the transition from a lying to a sitting position), movement, or ambulation. Following a period of several minutes, the elevated muscle tone typically diminishes or returns to a state of normality. This intermittent increase in muscle tone can result in motor dysfunction and significant difficulty in performing activities of daily living [2, 3]. Despite the clinical relevance of this condition, there is a paucity of high-quality studies investigating the incidence and risk factors of DS in SCI patients. This deficiency can be attributed to three key factors: firstly, the challenges clinical practitioners face in recognizing DS; secondly, the limited awareness of assessment tools [4–6]; and thirdly, a lack of understanding of the underlying mechanisms contributing to its development [7].

It seems probable that the reticulospinal tract (RST) is the principal supra-medullary exposure factor responsible for the development of DS following SCI. The RST, which originates mainly from the pontomedullary reticular formation [8, 9], is the main fiber bundle for the regulation of posture and the control of movement [10]. A recent study used the auditory startle reflex (ASR) to reflect the functional status of the RST. It was observed that up to 70% of patients with chronic incomplete injuries with American Spinal Injury Association (ASIA) impairment scale (AIS) C or D exhibited quadriceps spasticity and a significantly shortened ASR response time, indicating that the RST was in a highly sensitive state [11]. Another study employed stretch functional magnetic resonance imaging (Stretch-fMRI), a recently developed technology designed to examine the functionality of the RST. Stretch-fMRI is a novel technique that combines robotic perturbations with electromyography and fMRI to simultaneously quantify muscle and neural activity evoked by stretch reflexes during a brief period of posture change [12]. This study proposes that the RST may be involved in the regulation of dynamic spasticity. The aforementioned studies indicate that the RST plays a pivotal role in the formation of DS. However, the precise mechanism by which the RST affects the spinal cord during posture changes or movement to cause DS remains unclear.

Disorders in the spinal cord proprioceptive circuit may be a key intramedullary exposure factor in the formation and development of DS [13, 14]. Proprioception can be defined as the sense of the position of a body part in space, the movement of a body part, and the sensation of vibration. Proprioceptive signals are initially detected by proprioceptors (such as muscle spindles and tendon organs), then transmitted to the posterior cord of the spinal cord through peripheral nerves, and then transmitted upward to the medulla oblongata through the cuneate fasciculus and thin fasciculus of the posterior column of the spinal cord. Prior research has indicated that spinal cord stimulation (SCS) can effectively regulate spasticity by improving proprioceptive input [7, 15]. Our team previously found that patients who underwent SCS exhibited a notable improvement in DS phenomena associated with posture changes. SCS is positioned in the posterior cord of the spinal cord, and the target muscle can be selectively stimulated by adjusting the electrode stimulation site [16]. The intensity and frequency of the current can be modified to enhance proprioceptive input, which in turn can alleviate DS.

In light of these findings, the present study hypothesizes that RST may affect proprioception after SCI, causing posture changes and the occurrence and development of movement-related DS. To verify this theory, this trial used a prospective observational cohort study, mainly using MRI to examine the DTI indicators of the spinal RST and posterior columns, while evaluating DS to explore its correlation and possible predictive factors. At the same time, we further explored the impact of DS on the recovery of spinal cord function.

Methods

Study design and setting

The current study is a 12-month, prospective, noninterventional cohort study to be conducted between October 2024 and December 2026 at Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Centre), a 1000-bed tertiary rehabilitation hospital in Shanghai, China.

The primary outcome measures will be spinal MR imaging and dynamic spasticity data, collected from SCI patients at baseline, 3 months, 6 months, and 12 months. The study will be designed, implemented, and reported following the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) [17] criteria. A flow chart of the study procedure is provided in Fig. 1.

Fig. 1.

Flow chart of the study design. Abbreviations SCI: spinal cord injury; DS: dynamic spasticity; AIS: American Spinal Injury Association (ASIA) impairment scale; RST: reticulospinal tract; ASR: auditory startle reflex; SWV: shear wave velocity; DTI: diffusion tensor imaging

Sample size calculation

This study aims to investigate the exposure factors for DS in hospitalized patients with SCI. In a preliminary trial, we found that approximately 50% of patients with AIS scores from B to D experience DS. The sample size calculation was conducted using G*Power software (version 3.1.9.2; Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany). With a significance level of α = 0.05 (two-tailed) and a power (1–β) of 80%, we determined that a minimum sample size of 78 individuals in both the DS and non-DS groups would be needed to detect an effect size of 0.40. To prevent data bias, we increased the sample size by 10% for each group, resulting in 86 patients per group. Therefore, our study will initially screen SCI patients based on AIS ratings, and since approximately 50% of patients with AIS ratings of B to D are expected to have DS, we aim to enroll a total of 172 participants.

Participants

Inclusion and exclusion criteria

The inclusion criteria for individuals with SCI were as follows: (a) 18∼75 years old; (b) diagnosis of thoracic spinal cord injury by CT or MRI; (c) presence of limb motor and sensory dysfunction (AIS B-D); (d) disease course exceeding one month (from SCI onset to first assessment); and (e) agreement to participate in this study and signed the informed consent form. Exclusion criteria: (a) patients with injury site in the cone or cauda equina; (b) patients with other diseases that may precipitate spasticity, such as stroke; (c) patients with spasticity caused by cold, mental stress, pain, etc.; (d) patients with mental illness and other reasons who are unable to cooperate with examination and rehabilitation assessment; (e) patients with claustrophobia and other reasons who are unable to complete MRI examination.

Recruitment and sample selection

The study will recruit hospitalized patients with SCI from Tongji University Affiliated Yangzhi Rehabilitation Hospital starting in October 2024. Eligible participants will be screened and enrolled consecutively based on the following inclusion and exclusion criteria. During hospitalization, eligible patients will be approached by a research team member, who will explain the study objectives, procedures, and follow-up requirements. Patients who meet the inclusion criteria and agree to participate will sign an informed consent form and undergo baseline assessments. To assess the external validity of the recruited sample of participants, age and gender will be collected for those participants who refuse to participate in the study.

Upon receipt of the signed informed consent form, participants will be registered in the electronic case report form (eCRF), and their basic information will be recorded at baseline. All eligible patients will undergo initial screening by evaluating their clinical history, physical examination, and imaging results, including CT or MRI scans, to confirm thoracic spinal cord injury. The doctor will assess the MR data, ASR, spasticity indicators, and other motor function-related indicators. Follow-up will continue through in-hospital assessments, as well as telephone and WeChat consultations after discharge, at 3, 6, and 12 months post-initial assessment. Participants will receive reminders or be contacted by phone at subsequent testing time points. Measurements are recorded by the nurse specialist in the electronic patient record (Table 1).

Table 1.

Summary of data collection plan in the cohort

	Enrolment	Follow-up
Timepoint	Healthy control	1 month	3month	6month	12month
Enrolment
Eligibility screen	×	×
Informed consent	×	×
Assessments
MRI (T1W, T2W, ME-GRE, GREMT1/MT0/T1w, DTI)	×	×
Spasticity assessment
PSFS		×	×	×	×
VAS		×	×	×	×
MAS		×	×
MTS		×	×
Electrophysiological evaluation
ASR		×	×
H-reflex		×	×
Shear wave velocity		×	×
Overall functional recovery evaluation
AIS grade		×	×
ICF		×	×
Quantitative gait analysis		×	×
Observational gait analysis		×	×
Ten-meter walk test		×	×
TUG		×	×
BBS		×	×
SCIM		×	×	×	×
MBI		×	×	×	×
SF-36		×	×	×	×
Basic characteristic
Age	×	×
Gender	×	×
Height, Weight	×	×
Education	×	×

Abbreviations DTI: Diffusion tensor imaging; PSFS: Penn spasm frequency scale; VAS: visual analog scale; MAS: modified Ashworth scale; MTS: modified Tardieu scale; ASR: Auditory startle reflex; SWV: Shear wave velocity; AIS: American spinal injury association (ASIA) impairment scale; ICF: International Classification of Functioning, Disability and Health scale; TUG: Timed Up and Go Test; BBS: Berg balance scale; SCIM: spinal cord independence measure; MBI: Modified Barthel index; SF-36: 36-item short form health survey

Each participant’s data file will be assigned a unique number and stored in a secure and accessible place. Patient privacy and data security will be ensured during the study.

Outcome measures

Primary outcomes

Microstructural changes reflected by DTI of the RST and proprioception in the DS group compared to the non-DS group.

Secondary outcomes

Correlation of ASR, H-reflex, shear wave velocity (SWV), and motor functional parameters with DS.

MRI protocol

This study will use a Siemens 3.0T (Vida) MRI scanner with a 20-channel coil for data acquisition. All participants will undergo MRI examinations at 1 month and 3 months after enrollment. The protocol adopted in this study follows the parameters suggested by the Spinal Cord Toolbox (SCT) team [18]. Enrolled patients will receive MRI scans, including DTI, ME-GRE, GRE-MT1/MT0/T1w, T1-weighted, and T2-weighted sequences, to obtain imaging characteristics (Fig. 2). This study uses a Siemens 3.0T (Vida) MRI scanner with a 20-channel coil for data acquisition. Detailed MRI information is provided in Table 2.

Fig. 2.

Spine cord MR series images. A. T1-weighted sagittal localization image; B. T2-weighted sagittal localization image; C. Transverse ME-GRE; D. Transverse GRE-MT1; E. Sagittal DTI image; F. Transverse DTI image. Abbreviations ME: multi-echo; GRE: gradient recalled echo; MT: magnetization transfer; DTI: diffusion tensor imaging

Table 2.

Information collection of imaging data

Parameter	Value
Manufacturer	SIEMENS
Model	Vida
Field strength	3.0T
Software	XA20
Voxel size (mm)
DTI	0.9 × 0.9 × 5.0
T1w (3D)	1.0 × 1.0 × 1.0
T2w (3D)	0.8 × 0.8 × 0.8
ME-GRE (2D)	0.5 × 0.5 × 5.0
GRE-MT1/MT0/T1w (3D)	0.9 × 0.9 × 5.0
DTI parameters
Receiver coil channels	20
Directions	30
b value	800 s/mm2

Abbreviations DTI: diffusion tensor imaging; T1W: T1-weighted image; T2W: T2-weighted image

Three-dimensional (3D) gradient-echo T1-weighted image

TR/TE 2000/3.72 ms, number of averages: 1, flip angle: 9°, voxel size: 1.0 × 1.0 × 1.0 mm³, field of view [FOV] 320 × 260 × 192 mm³, bandwidth 150 Hz/Px, phase encoding direction: A > > P.

Three-dimensional (3D) gradient-echo T2-weighted image

TR/TE 1500/120 ms, number of averages: 1.4, flip angle: 120°, voxel size: 0.8 × 0.8 × 0.8 mm³, field of view [FOV] 256 × 256 × 51 mm3, bandwidth 625 Hz/Px, phase encoding direction: H > > F.

ME-GRE(2D)

TR/TE 600/14 ms, number of averages: 2, flip angle: 30°, voxel size: 0.5 × 0.5 × 5.0 mm³, field of view [FOV] 224 × 224 × 75 mm3, bandwidth 260 Hz/Px, phase encoding direction: A > > P.

GRE-MT1/MT0/T1w (3D)

TR/TE 35/3.16 ms, number of averages: 1, flip angle: 9°, voxel size: 0.9 × 0.9 × 5.0 mm³, field of view [FOV] 230 × 230 × 110 mm3, bandwidth 260 Hz/Px, phase encoding direction: A > > P.

Diffusion tensor imaging (DTI)

TR/TE 580/75 ms, FOV 86 × 32mm², voxel size 0.9 × 0.9 × 5.0 mm³, 30 gradient directions, single shell with max b = 800 s/mm², number of b0 images = 5, acquisition mode MDDW, phase encoding direction A > > P.

Spasticity assessment

Penn spasm frequency scale (PSFS)

The PSFS is a self-reported or clinician-rated scale used to assess the frequency of dynamic spasticity in patients with spinal cord injury (SCI) or other neurological disorders. It is widely used in SCI patients, particularly for assessing spasticity in the lower extremities. The classification standards included 0, 1, 2, 3, and 4 [19] (Supplemental Table 1).

Visual analog scale (VAS)

The modified VAS is a measurement tool that employs a 10-cm straight line on a white paper, with the two ends labeled “no dynamic spasticity” and “worst dynamic spasticity”. The subject is instructed to mark the line according to the degree of dynamic spasticity they perceive, with the distance from the starting point to the mark representing the quantified degree of spasticity [20].

Modified Ashworth scale (MAS)

The MAS is the most commonly utilized clinical scale for the assessment of muscle tone. The classification standards included 0, 1, 1+, 2, 3, and 4 [21, 22] (Supplemental Table 2).

Modified Tardieu scale (MTS)

The test is comprised of three key components, namely the velocity of stretch, the quality of the muscle reaction, and the angle of the muscle reaction. The rater commenced the test by moving the joint in a slow, gradual manner (defined as V1) through its full range of motion. The angle was subsequently measured with a universal goniometer by a second physician, who positioned the goniometer close to the joints and recorded the values. The angle of the full range of motion was designated as R2. Subsequently, the rater moved the joint with the greatest possible speed (defined as V3) in the same direction and through the same full movement arc. The angle of muscle reaction (either a clear catch or clonus) was measured with the goniometer and recorded as R1. The distinction between R2 and R1 (R2-R1) represents the dynamic tonic component of spasticity. An increase in the spasticity angle is indicative of heightened spasticity in the muscle [22, 23] (Supplemental Table 3).

Electrophysiological evaluation

Auditory startle reflex (ASR)

Participants must be able to tolerate a period of sitting for a minimum of 40 min. On the day of the assessment, patients are required to wear loose-fitting trousers, preferably shorts, and must not present with a hearing loss or significant cognitive impairment.

The subjects were seated in a chair with a backrest, ensuring that the back was fully supported and the head was in a neutral position. The hip and knee joints were maintained in a position of 90° flexion. Subjects were instructed to close their eyes and relax, while avoiding drowsiness, and to record the surface electromyography signals of the gracilis, rectus femoris, and medial gastrocnemius muscles. The subjects were provided with headphones and received five sound stimuli. The interval between two consecutive sound stimuli was randomly generated within the range of 2–3 min. The frequency of the sound stimulation was 1 kHz, the duration of the platform was 50 ms, the rise and fall time was less than 0.1 ms, and the sound pressure level was 105 dB SPL. The electromyographic signals within 400 ms of each sound stimulation were subjected to a band-pass filter with a passband of 10 Hz to 10 kHz and sampled at a rate of 48 kHz with a sensitivity of 0.5 mV/div (Keypoint 9033A07, Natus Manufacturing Limited, Denmark). The temperature of the indoor environment was maintained at a constant 24–26 °C [24].

Data parameters will include the averaged latency, amplitude, and duration of ASR waveforms from both target muscles, as well as the probability of ASR occurrence.

H-reflex

The patient is positioned prone with both legs extended, thereby ensuring that the calf is fully relaxed and supported by a cushion. The skin is disinfected by cleansing it with an alcohol solution. The recording electrode is positioned over the mid-belly of the soleus muscle, the reference electrode is placed on the Achilles tendon, and the ground electrode is situated between the recording and stimulating electrodes. The stimulating electrode is then secured in the popliteal fossa, with the cathode oriented in a proximal direction. The intensity of the stimulation is increased gradually until the maximum H-reflex is elicited without the presence of an M-wave. It is customary to perform several consecutive recordings with intervals of 3–5 s, selecting the measurement with the shortest latency. The parameters are set to a sensitivity of 0.5 mV, a scanning speed of 10 ms/cm, and a time constant of 1 ms (Keypoint 9033A07, Natus Manufacturing Limited, Denmark) [25].

Shear wave velocity (SWV)

A Fortis Expert ultrasound system (GE LOGIQ, China) equipped with a 5- to 12-MHz linear transducer (L3-12-D, GE LOGIQ) was used to obtain B-mode scanning images and SWV values from both rectus femoris, gracilis, biceps brachii, and gastrocnemius.

Overall functional recovery evaluation

The evaluation of overall functional recovery in individuals with SCI is critical for understanding their progress and guiding rehabilitation efforts. This comprehensive assessment encompasses a variety of validated tools that measure various aspects of physical function, mobility, and quality of life.

ASIA impairment scale (AIS) grade

The AIS grade is primarily used to ascertain the degree of SCI (spinal cord injury) and can be classified into five categories: A, B, C, D, and E. A denotes a complete injury, while B-D indicates incomplete injuries, with the severity decreasing in successive order. Category E signifies normal sensorimotor function [26] (Supplemental Table 4).

International Classification of Functioning, Disability and Health (ICF) scale

The ICF scale, which was established and promulgated by the World Health Organization, offers a theoretical model for comprehending the impacts of impairments from biological, psychological, and social perspectives [27, 28].

Quantitative gait analysis

Electromyogram (EMG) activity during the act of walking was acquired bilaterally using 8-channel wireless sensors (Noraxon Ultium) placed over the rectus femoris, semitendinosus, tibialis anterior, and medial gastrocnemius muscles. Kinematic data were obtained through the use of a three-dimensional motion capture system (Vicon Motion Systems) [16].

Observational gait analysis

It is recommended that frontal and lateral views of the patient be collected while the patient is walking. To analyze the quality of gait from video recordings, a panel of physiotherapists was asked to score different walking trials using items in a validated scoring sheet, which is described in Supplemental Table 5 [16].

Ten-meter walk test

Walking speed was assessed by a timed ten-meter walk test without any external assistance. The participant was instructed to walk with the preferred assistive device as fast as he could.

Timed up and go test (TUG)

The TUG test is used to identify balance and gait disorders and assess a patient’s risk of falling. It consists of three components: evaluating lower extremity strength and function, assessing balance and stability, and measuring functional mobility. The total time taken to complete the test reflects the subject’s ability to perform daily activities effectively [29, 30].

The Berg balance scale (BBS)

The BBS is a widely used clinical assessment instrument designed to evaluate an individual’s balance abilities and fall risk, particularly among the elderly and neurorehabilitation patients. The BBS consists of 14 tasks, each scored based on the observer’s assessment of the subject’s performance, with a total score of 56 points [31].

Spinal cord independence measure (SCIM) version III

The SCIM III is a validated assessment tool designed to evaluate functional independence in individuals with SCI. It consists of three primary components: self-care, which includes activities such as bathing, dressing, grooming, and toileting; respiration and sphincter management, assessing the individual’s ability to manage breathing and bowel/bladder functions; and mobility, which evaluates the ability to perform transfers and navigate in a wheelchair [32].

Modified Barthel index (MBI)

The MBI is a widely used tool for assessing an individual’s ability to perform activities of daily living. The maximum score is 100 which consists of 10 items associated with different activities such as feeding, bathing, ambulation, dressing, and bowel and bladder control. Higher scores indicate greater independence in daily activities [33].

36-item short form health survey (SF-36)

The SF-36 is a questionnaire designed to measure health-related quality of life. It consists of 36 items across eight health concepts: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. Each item is scored on a scale, allowing for the calculation of physical and mental health component scores, as well as a profile of scores for the individual domains [34].

Data management

All recorded data will be collected in the form of paper CRFs. Two authorized clinical staff members will input the data into an electronic CRF. The data will be securely stored in a password-protected database. Quality control measures will include regular audits of the data entry process and training sessions for researchers to ensure consistency in data collection. Inputted data will undergo reliability checks, monitoring, and medical review. Any unreliable or missing data will be queried.

Statistical analysis

Descriptive statistics

The data will be analyzed descriptively and divided into a DS group and a non-DS group. Measurement data will be expressed as mean ± SD (standard deviation), median (quartile), or number [%] (N [%]). Data comparisons will be performed using a T-test, rank sum test, or chi-square test. P-value < 0.05 is considered to indicate a statistically significant difference.

Correlation analysis

Pearson correlation coefficients or Spearman rank correlation coefficients will be employed to assess the correlation between DTI metrics of the RST and proprioception (dorsal columns) and the dynamic spasticity assessment scale. P-value < 0.05 is considered to indicate a statistically significant difference.

Regression analysis and predictive model

Multiple linear regression analysis or Cox regression analysis will be conducted to explore the predictive effects of DTI parameters related to the RST and proprioception on dynamic spasticity, while controlling for potential confounding factors to establish a predictive model. Model performance will be evaluated using accuracy, sensitivity, specificity, ROC curves, and AUC values. Internal validity will primarily be assessed through bootstrapping methods. P-value < 0.05 is considered to indicate a statistically significant difference.

Sensitivity analysis

Sensitivity analysis will be performed by adjusting model parameters and analytical methods to verify the robustness of the results. All data will be processed using SPSS version 20.0, with a significance level set at P < 0.05.

Monitoring of the safety and potential risks

MRI is generally considered to be a safe procedure; however, patients with implanted devices or metal fragments must be carefully screened before undergoing the examination. Mild adverse effects, such as claustrophobia or anxiety, may manifest; therefore, the staff must be prepared to assist. Similarly, electrophysiological evaluation is considered a safe procedure; however, patients may experience discomfort or soreness at the electrode sites. The implementation of appropriate techniques can assist in the reduction of these risks. Ultrasound is a non-invasive procedure with minimal associated risks. Nevertheless, patients should be observed for any indications of an allergic reaction to the gel employed. It is of the utmost importance to maintain continuous communication regarding the patient’s comfort and any potential symptoms, to guarantee the safety of the patient throughout the procedure.

Discussion

This study is a clinical study of DS occurring during postural changes or movements after SCI. It is the first cohort study to explore the relationship between microstructural changes of the RST, proprioception, and DS in SCI patients. While previous research has focused on the variability of DS recovery post-SCI, our understanding of the underlying microstructural changes remains insufficient. This study aims to fill this knowledge gap and provide a more comprehensive perspective to help improve the assessment and rehabilitation strategies of DS following SCI.

Method selection for evaluating the microstructure of spinal cord RST and proprioception

The ASR can reflect the overall function of the RST [11], but it does not provide insight into microstructural changes within the RST, particularly in different segments of the spinal cord. Similarly, although stretch-fMRI can be used to assess RST function [12], its technical and equipment demands limit its feasibility in large-scale clinical trials. Furthermore, current assessments of spinal proprioception are largely based on subjective scales that cannot assess microstructural changes in the dorsal columns of the spinal cord. To overcome these limitations, this study has opted for spinal DTI, which facilitates localized and segmental assessment of microstructural changes in fiber tracts by observing the diffusion of water molecules [35]. However, the use of spinal DTI presents several challenges. For example, some patients have spinal implants that affect image quality, reducing the comparability of local DTI data. In addition, spinal DTI technology is less mature than brain DTI, with fewer established parameters and protocols, meaning that spinal DTI remains in an exploratory phase.

To address these issues, this study includes only patients with thoracic and lumbar spinal cord injuries, and all patients undergo uniform MRI scans of the cervical spine and brainstem [18]. In addition, we have adopted MRI acquisition protocols [18] suggested by the Spinal Cord Toolbox (SCT) team [36]. These protocols include T13w (3D) for spinal cord localization, T2w (3D) for observation of spinal cord atrophy, ME-GRE (2D) for grey matter atrophy, MT for detection of white matter demyelination and DTI for assessment of microstructural changes in the RST and proprioceptive fiber bundles [18].

Challenges in the clinical assessment of dynamic spasticity

In clinical practice, the assessment of dynamic spasticity presents several challenges [6]. Firstly, although the PSFS allows assessment of spasticity frequency, it relies on patient self-report, which can be influenced by cognitive ability and subjective perception [37]. Secondly, although the VAS provides a tool for patients to quantify the severity of spasticity, it is also based on subjective experience and cannot objectively measure the physiological changes associated with spasticity. Given the limitations of current rating scales and instruments for measuring dynamic spasticity, the PSFS and VAS remain an indispensable scale for the assessment of DS [20]. The MAS, commonly used to assess muscle tone during passive stretching, is a standard tool in clinical practice but has limited sensitivity in capturing dynamic spasticity, particularly when spasticity varies frequently [1, 6]. The MTS can assess muscle response at different speeds and better reflect spasticity under dynamic conditions, but it is difficult to assess changes in dynamic muscle tone during changes in posture, movement, or walking [22]. Thus, while each of these scales has its strengths, they collectively fall short of providing a comprehensive assessment of dynamic spasticity, particularly in accurately quantifying spasm frequency, intensity, and dynamic characteristics.

To better address DS in patients during postural changes, transfers, or walking, we have implemented the following measures. Firstly, recognizing that many patients may not fully understand what constitutes spasticity. They often confuse neuropathic pain with spasticity or misinterpret normal dynamic changes in muscle tone changes as spastic episodes. Therefore, we have conducted educational sessions on the identification and recognition of spasticity. Secondly, we have incorporated three additional dimensions into the PSFS assessment, focusing on the frequency of spasticity occurrences during postural changes, movement, and walking. This modification aids in capturing a more accurate reflection of the true frequency of DS. Furthermore, for patients capable of walking, we will perform a 3D gait analysis to provide a more comprehensive evaluation of dynamic spasticity. Additionally, two trained therapists will be involved in the assessment process to ensure consistency of assessment.

Clinical and research implications of the study

The significance of this study lies in its contribution to understanding the intricate relationship between dynamic spasticity and walking function in patients with SCI. As research increasingly focuses on spinal SCS for improving ambulation in individuals with paraplegia [16], the effective control of dynamic spasticity emerges as a crucial prerequisite for achieving optimal walking performance [15]. Previous studies have indicated that SCS can have a positive impact on spasticity, suggesting that targeted neuromodulation may enhance not only muscle control but also overall functional recovery [15, 16]. This research aims to delve deeper into the mechanisms by which proprioception and the RST interact with dynamic spasticity following SCI. By elucidating these relationships, the findings will provide a foundational framework for future studies exploring the role of SCS and other therapeutic interventions in managing spasticity and enhancing motor function.

Understanding how proprioceptive feedback and the integrity of the RST contribute to dynamic spasticity can inform clinical practices and rehabilitation strategies. This study’s insights may guide the development of tailored therapeutic approaches that integrate neuromodulation techniques like SCS with physical rehabilitation, ultimately improving the quality of life for individuals with SCI.

Limitations and future work

This study has several limitations that should be acknowledged. Firstly, reliance on self-report measures such as the PSFS and VAS may introduce bias as these assessments are dependent on patient perception and cognitive ability. In addition, the focus on specific levels of injury (thoracic and lumbar) may not fully capture the complexity of dynamic spasticity in patients with cervical SCI. Finally, the assessment of dynamic spasticity remains challenging due to the variability of symptoms, which may not be adequately represented in a controlled clinical setting. Future research should aim to address these limitations by including more diverse samples and utilizing more objective measures of dynamic spasticity.

In conclusion, this study provides valuable insights into the relationship between dynamic spasticity and spinal cord recovery following injury. By employing a comprehensive approach that combines advanced imaging techniques with standardized functional assessments, we have begun to elucidate the complexities of dynamic spasticity in this population. Despite the limitations noted, the findings highlight the need for enhanced assessment strategies and targeted rehabilitation interventions for individuals experiencing dynamic spasticity after spinal cord injury.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Abbreviations

DS

Dynamic Spasticity

SCI

Spinal Cord Injury

DTI

Diffusion Tensor Imaging

SCS

Spinal Cord Stimulation

RST

Reticulospinal Tract

AIS

American Spinal Injury Association (ASIA) impairment scale

Stretch-fMRI

Stretch Functional Magnetic Resonance Imaging

PSFS

Penn Spasm Frequency Scale

VAS

Visual Analog Scale

MAS

Modified Ashworth Scale

MTS

Modified Tardieu Scale

ASR

Auditory Startle Reflex

SWV

Shear Wave Velocity

ICF

International Classification of Functioning, Disability and Health scale

TUG

Timed Up and Go Test

BBS

Berg Balance Scale

SCIM

Spinal Cord Independence Measure

MBI

Modified Barthel Index

SF-36

36-item Short Form health survey

eCRF

Electronic Case Report Form

Author contributions

Jingrong Wang and Lianghua Fan: writing original draft. Jing Sun: spinal MRI data collection and analysis. Jibao Chen, Ying Wang, and ZengQiang OuYang: assessment and data compilation of spasticity and overall function. Zhihong Yuan: Electrophysiological data collection and analysis. Changqin Sun: Ultrasound data collection and analysis. Lingjing Jin and Yue Wang: writing, review & editing, Supervision, Conceptualization. All authors read and approved the final manuscript.

Funding

This study was supported by the National Key Research and Development Program (2023YFC3604500/2023YFC3604505), the Natural Science Foundation of Shanghai’s “Science and Technology Innovation Action Plan” (23ZR1459400), the Fundamental Research Funds for the Central Universities (22120220567), the National clinical key specialty construction project of China (Z155080000004), the Shanghai Rehabilitation Medical Research Center (Top Priority Research Center of Shanghai) (2023ZZ02027), the Shanghai Clinical Research Ward (SHDC2023CRW018B), and the Shanghai Hospital Development Center Foundation—Shanghai Municipal Hospital Rehabilitation Medicine Specialty Alliance (SHDC22023304).

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

This study will follow the ethical criteria for medical research involving human subjects of the Declaration of Helsinki and the ethical criteria for medical research of Shanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center) in the development of the study. This study was approved by the Ethics Review Committee of Shanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center) (No. YZ2024-073) and is registered in the Clinical Trial Registry (No. ChiCTR2400090724). All subjects will be required to agree to participate in the study and provide informed consent.

Consent for publication

All the detection personnel and subjects in the figures of this study fully understood the purpose of this research, agreed to appear in the figures of this study, and signed the Consent to Publish Declaration.

Competing interests

The authors declare no competing interests.