Dural sac decompression and spinal cord untethering for treating obsolete spinal cord injury: protocol for a prospective, multicenter cohort study
Xin-ran Ji, Pei-fu Tang, Ning Lu
Chinese PLA General Hospital, Beijing, China
|Date of Web Publication||2-Aug-2017|
Chinese PLA General Hospital, Beijing
Chinese PLA General Hospital, Beijing
Source of Support: This study was supported by the Major Project of Beijing Science and Technology Commission of China, No. D16110000 2816005., Conflict of Interest: None
Background and objectives: Spinal cord injury is an irreversible pathological process. Clinical findings in recent years have demonstrated that dural sac decompression can scavenge subdural hematoma and necrotic tissue, alleviate compression of the injured spinal cord, create a favorable microenvironment for regeneration of nerve repair, and promote recovery of neurological function. Therefore, this trial aims to examine the effect of dural sac decompression and spinal cord untethering for treating obsolete spinal cord injury.
Design: This is a prospective, multicenter cohort study.
Methods: Seventy-two patients with obsolete spinal cord injury from four clinical sites in China will be assigned to the trial group (n = 36) or control group (n = 36) according to therapeutic methods. Patients in the trial group will receive dural sac decompression and spinal cord untethering. Patients in the control group will undergo conservative treatment. All patients were followed up for 24 months.
Outcome measures: The difference in American Spinal Injury Association scores between 3 months after treatment and before treatment is the primary outcome measure. For secondary outcome measures, the autonomic nervous scoring scale, the Visual Analog Scale, an electromyogram below the injured plane, somatosensory evoked potential, motor evoked potential, functional independent measure, the ID pain self-rating scale, the modified Ashworth Scale for grading spasticity, and the Penn Spasm Frequency Scale will be applied 3 months before treatment, and 1, 3, 6, 9, 12, 18, and 24 months after treatment. Urodynamic testing will be performed.
Discussion: This trial is expected to provide an experimental basis for dural sac decompression and spinal cord untethering in patients with obsolete spinal cord injury.
Ethics and dissemination: The protocols were approved by the Ethics Committee of Chinese PLA General Hospital on May 11th, 2016 (approval No. S2016-024-01). The study design was finished in April 2016. Recruitment of patients began in April 2017. Follow-up will be completed in December 2018. Data analysis will be completed in December 2019. The results of the trial will be published in a peer-reviewed journal and will be disseminated via various forms of media.
Trial registration: This trial has been registered in the Chinese Clinical Trial Registry (registration No. ChiCTR-ONC-17010479) on January 19th, 2017. Recruitment of patients is ongoing.
Keywords: clinical trial; obsolete spinal cord injury; dural sac decompression; spinal cord untethering; American Spinal Injury Association score; prospective, multicenter cohort study
|How to cite this article:|
Ji Xr, Tang Pf, Lu N. Dural sac decompression and spinal cord untethering for treating obsolete spinal cord injury: protocol for a prospective, multicenter cohort study. Asia Pac J Clin Trials Nerv Syst Dis 2017;2:117-23
|How to cite this URL:|
Ji Xr, Tang Pf, Lu N. Dural sac decompression and spinal cord untethering for treating obsolete spinal cord injury: protocol for a prospective, multicenter cohort study. Asia Pac J Clin Trials Nerv Syst Dis [serial online] 2017 [cited 2021 May 12];2:117-23. Available from: https://www.actnjournal.com/text.asp?2017/2/3/117/211593
| Introduction|| |
Spinal cord injury is one of the most serious complications of spinal injuries and often results in severe dysfunction of the limbs below the injured segment. The injured spinal cord is subjected to primary injury, such as epidural fracture fragments and spinal cord shear force, and secondary injury, such as intradural edema and hematoma. Simultaneously, the injured spinal cord is limited by a bony spinal canal and the dural sac. Therefore, inside and outside of the spinal cord are compressed, and the intramedullary pressure increases. This results in dural sac or subarachnoid space stenosis and adhesion, cerebrospinal fluid occlusion, and arteriovenous obstruction. These processes promote local ischemia and hypoxia, and aggravate secondary injury. Ischemia and hypoxia, in turn, aggravate edema, hematoma, necrosis, and intramedullary hypertension, forming a vicious circle and leading to chronic dysfunction of multiple organs and systems. Additionally, permanent functional changes, such as sensory and motor dysfunction below the injured plane can occur, and these decrease the patient's quality of life (Yu and He, 2015). Obsolete spinal cord injury in the thoracolumbar segment is often accompanied by intradural adhesion, traction of fibrous cords, scarring, softening, and cysts after trauma, and causes barriers to rehabilitation (Zhang et al., 2000).
Obsolete spinal cord injury, especially complete spinal cord injury, has little chance of recovery, and there is no uniform treatment for repair. Dural sac decompression plus spinal cord untethering releases the constraint of spinal dura mater on spinal cord tissue, scavenges hematomas and necrotic tissue, reduces the oppression of injured spinal cord, and decreases dural sac pressure. This technique also promotes blood perfusion of the spinal cord, reduces sustained stimulation to the spinal cord by inflammatory mediators, reduces spinal cord ischemia and hypoxia, decreases or inhibits the spread of secondary injury, and further prevents cell necrosis. Furthermore, dural sac decompression plus spinal cord untethering preserves residual spinal cord tissue, creates a good microenvironment for nerve repair and regeneration, and promotes the recovery of nerve function (Perkins and Deane, 1988; Zhu et al., 2008; Jones et al., 2012; Soubeyrand et al., 2013). Our team, the obsolete spinal cord injury special research group of the Department of Orthopedics, Chinese PLA General Hospital, has completed dural sac decompression and spinal cord untethering for treating obsolete spinal cord injury since January 2016. We have found that sensory and motor nerve function significantly improves in approximately 1/3 of patients.
The Department of Orthopedics of Chinese PLA General Hospital, China will lead this prospective, multicenter cohort study. The study will be completed in the First Affiliated Hospital of Chinese PLA General Hospital, Beijing Chao-Yang Hospital of Capital Medical University, Beijing Institute for Brain Disorders, and China Rehabilitation Research Center, China. This study aims to observe the efficacy of dural sac decompression and spinal cord untethering for treating obsolete spinal cord injury.
| Methods/Design|| |
This prospective, multicenter cohort study will be completed in the First Affiliated Hospital of Chinese PLA General Hospital, Beijing Chao-Yang Hospital of Capital Medical University, Beijing Institute for Brain Disorders, and China Rehabilitation Research Center. Seventy-two patients with obsolete spinal cord injury, who meet the inclusion criteria, will be equally assigned to the trial and control groups.
Patients in the trial group will receive dural sac decompression and spinal cord untethering. Patients in the control group will undergo conservative treatment. Evaluation will be carried out before treatment, and 1, 3, 6, 9, 12, 18, and 24 months after treatment.
Primary and secondary outcome measures: The difference in American Spinal Injury Association (ASIA) scores between 3 months after treatment and before treatment is the primary outcome measure. For secondary outcome measures, the autonomic nervous scoring scale, the Visual Analog Scale, an electromyogram below the injured plane, somatosensory evoked potential, motor evoked potential, functional independent measure, the ID pain self-rating scale, the modified Ashworth Scale for grading spasticity, and the Penn Spasm Frequency Scale will be applied 3 months before treatment, and 1, 3, 6, 9, 12, 18, and 24 months after treatment. Urodynamic testing will be performed.
We will recruit patients with obsolete spinal cord injury, who are treated in the First Affiliated Hospital of Chinese PLA General Hospital, Beijing Chao-Yang Hospital of Capital Medical University, Beijing Institute for Brain Disorders, and China Rehabilitation Research Center.
Patients presenting with all of the following criteria will be considered for inclusion in the study.
- Symptoms and signs are in accordance with International Standards for Neurological Classification of Spinal Cord Injury (Kirshblum et al., 2011), issued by the American Spinal Injury Association. The injury site is C5–T12, as detected by magnetic resonance imaging
- American Spinal Injury Association (ASIA, 2011) grades A, B, and C
- Good cardiorespiratory function can withstand surgery and conservative treatment
- Course of disease is &62; 6 months
- Patients are aged between 16 and 50 years old
- Informed consent signed by the patient (guardian) or the patient&39;s family
Patients with one or more of the following conditions will be excluded from this study.
- Other central and peripheral nervous system diseases
- Severe injury to other regions or limbs
- Moderate and severe cognitive impairment
- Severe Alzheimer&39;s disease and Parkinson&39;s disease greatly affect walking ability
- Tumor- and infection-induced spinal cord injury
- Severe heart, lung, gastrointestinal, and liver and kidney dysfunction
- Patients with diabetes who require insulin therapy
- Mental disorder
- Pregnant women
- Participation in other clinical trials
Patients who meet one or more of the following criteria during the trial will be withdrawn from this study.
- Complications that affect determination of efficacy and safety or onset of diseases that affect the outcome
- The use of other therapies or drugs that affect determination of efficacy
The study design was finished in April 2016. Ethical approval was received in May 2016. Clinical registration was conducted in January 2017. Recruitment of patients began in April 2017. Follow-up will be completed in December 2018. Data analysis will be completed in December 2019.
Recruitment information will be disseminated through viral spread using WeChat&39;s Circles function. Potential participants will be able to contact the project manager via telephone.
The Baseline Information Is Shown in [Table 1].
Group assignment and treatment
Patients will be divided into the trial group and control group (n = 36). Patients, surgeons, and evaluators will be informed about the group assignment.
(1) Trial group: The patients will undergo dural sac decompression and spinal cord untethering. After general anesthesia, patients will be in the prone position. A posterior median longitudinal incision will be made, and the muscle on both sides of the spinous process will be peeled off. Scars on the surface of dural sac will be dissociated to expose the spinal dura mater on the injured segment. The spinal cord will be lightly compressed by a nerve dissector to determine the superficial softened area of the spinal cord. A longitudinal incision will be made on the dural sac. After dural sac suspension, adhesion of the arachnoid will be separated, untethered, and longitudinally incised. After removal of the hematoma and scar, the spinal cord will be exposed. The scar damaged softened area in the spinal cord will be identified, and a longitudinal incision will be gently made at the avascular region. The spinal cord will be separated and untethered at the depth of softened necrotic foci, and subjected to gentle, low-pressure irrigation and decompression. The spinal dura mater or artificial dura mater will be sutured using 5-0 vascular suture. Without leakage of cerebrospinal fluid, a gelatin sponge will be used for coverage. The wound will be washed with physiological saline. The drainage tube will be maintained in the wound, and then the wound will be sutured layer by layer.
(2) Control group: Patients will receive conservative treatment of passive activity, skin traction, and symptomatic treatment with drugs.
Evaluation will be carried out before treatment, and 1, 3, 6, 9, 12, 18, and 24 months after treatment.
Primary outcome measure
The difference in ASIA scores between 3 months after treatment and before treatment is the primary outcome measure. The ASIA publishes the International Standards for Neurological Classification of Spinal Cord Injury, and provides a neurological exam that is widely used to document sensory and motor impairment. The sensory score is used to examine the main points in each of the 28 skin areas on both sides of the body. Acupuncture sensation and light touch are checked at each key point. The total score is 112 on both sides. The motor score is applied to examine muscles at elbow flexion, extension of the wrist and elbow, finger flexion and abduction, hip flexion, knee extension, ankle dorsiflexion, plantar flexion, and plantar flexion of the ankle. The total score is 100 (ASIA, 2011).
Secondary outcome measures
- The differences in ASIA scores between 3, 6, 9, 12, 18, and 24 months after and before treatment will be determined. Autonomic nervous scoring scale: This scale is formulated by the ASIA and International Spinal Cord Society, and can assess autonomic nerve function, and bladder, intestinal tract, and sexual function (Alexander et al., 2009).
- Visual Analog Scale: This scale is used to assess pain. We will draw a long line of 10 cm on a piece of paper. One end is painless (0 points) and the other end represents a sharp pain (10 points). Subjects will be asked to draw a position on the line according to the degree of pain that they experienced, as Visual Analog Scale scores (Langley and Sheppeard, 1985).
- Electromyogram below the injured plane: Electromyography will be used to evaluate nerve and muscle excitation and conduction function.
- Somatosensory evoked potential: This is a nervous system response caused by various sensory stimuli, and is mainly used in the diagnosis of various nervous system diseases and monitoring of spinal surgery. The somatosensory evoked potential provides a unique means of investigating physiological anatomy for understanding cognition and function of somatosensory pathways and the sensory system (Hua et al., 2016).
- Motor evoked potential: We will perform a noninvasive neurophysiological examination of motor nerve system function. This examination can be used to analyze the degree of injury to spinal cord motor function and prognosis by observing the changes in latency and amplitude (Kothbauer, 2017).
- Functional independent measure: This is a scale for assessing functional independence. Functional independent measure scores contain self-care, sphincter control, mobility, motor ability, communication, and social cognition. The total score of this scale is 126. A lower score represents poorer function (Chumney et al., 2010).
- ID pain self-rating scale: This scale is an internationally available, simple, effective, and sensitive tool for patients with neuropathic pain. The total score ranges from −1 to 5. The scoring system is as follows: −1 to 0, neuropathic pain is unlikely; 1, neuropathic pain is not completely excluded; 2 to 3, neuropathic pain; and 4 to 5, highly considered as neuropathic pain (Portenoy, 2006).
- Modified Ashworth Scale for grading spasticity: This scale is the main clinical measure of muscle spasms in the nervous system. The total score ranges from 0–4. A low score represents normal muscle tension. A high score represents spasticity or increased passive movement resistance (Ansari et al., 2008).
- Penn Spasm Frequency Scale: This scale is used to assess the frequency of double lower extremity spasticity in patients with spinal cord injury and to understand the degree of spasticity. The scoring system is as follows: 0, no spasticity; 1, mild spasticity, induced by stimulation; 2, spasticity once every hour; 3, spasticity more than once every hour; 4, spasticity more than 10 times every hour (Penn et al., 1989).
- Urodynamic testing: This test is used to detect pressure, flow rate, and bioelectric activity of various parts of the urinary tract. Additionally, this test is used to understand the length and pressure distribution of the urethral sphincter, bladder retention, the change in bladder pressure, coordination of the degree of the detrusor and sphincter, and the urinary flow rate during micturition. Furthermore, urodynamic testing is used to observe lower urinary tract dysfunction (Zhang et al., 2015).
The schedule of outcome measurement assessments is shown in [Table 2].
A trial flow chart is shown in [Figure 1].
All of the preparatory work will be carried out in the start-up phase. During the trial, an inspector will focus on monitoring the test schedule at each center, ensuring trial implementation, and the integrity and authenticity of the data and reporting. This inspector will also monitor adverse reactions and follow-up. After the clinical trial, case report forms will be collected to check cohort migration. The inspector will establish a database and audit data entry.
Sample size calculation: In accordance with the formula , p1 and p0 are the expected rate of improvement in the trial and control groups, respectively (Liang et al., 2016). The letter p indicates the average improvement rate. q=1−p. Zα and Zβ: Under standard normal distribution, α (0.05) and β (0.1) are the corresponding normal variable Z boundary values, separately. We will calculate a final effective sample size of n = 131 per group. If we assume a patient loss rate of 20%, we will require 158 patients per group. Because of limitations in experimental funding and time, we will include 36 patients per group, with a total of 72 patients.
Statistical method: Measurement data will be expressed as mean ± standard deviation. Count data will be expressed as percentages. Data will be analyzed using SPSS 23.0 software (IBM Corp., Armonk, NY, USA). Normal distribution of data will be analyzed. Normally distributed data will be evaluated using the paired t-test. Non-normally distributed data will be evaluated using a two related samples nonparametric test (Wilcoxon). A P value of &60; 0.05 will be considered statistically significant. Results will follow the intention-to-treat principle.
Data validation: Patients who receive at least one treatment and have evaluation data after drug administration constitute a full analysis population. Efficacy-related missing data will be supplemented by data from the last observation.
Case report forms will be completed by clinical researchers, who will ensure accurate, complete, timely data entry, and they will then record data electronically using a double-data entry strategy. After data entry, statisticians will further check the integrity and accuracy of the data. The project manager will lock the database. A professional statistician will statistically analyze the electronic database. Appropriate data will be published at Beijing Municipal Science &38; Technology Commission, China within 6 months after completion of the trial.
All participants will strictly follow the protocols. Standard operating procedures will be used to ensure the implementation of quality control and quality assurance systems. All observational results and findings will be verified. Quality will be controlled during each stage of data processing.
Ethical requirements and informed consent
The protocols were approved by the Ethics Committee of Chinese PLA General Hospital on May 11th, 2016 (approval number: S2016-024-01). Written informed consent will be provided by patients or their family after they have indicated that they fully understand the treatment plan. The trial will be reported in line with the Consolidated Standards of Reporting Trials (CONSORT) 2010 guidelines and the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist (Additional file 1).[Additional file 1]
Deviations from clinical trial protocols and revisions to clinical trial protocols
Before and after treatment, the same assessment staff will be arranged to prevent measurement bias. Confounding factors, such as cause and course of disease and sex, which may affect the curative effect, will be discussed as independent variables in multivariate analysis. Data loss will be reduced, and the intention-to-treat principle will be used.
Direct access to source data and files
Through informed consent, subjects will authorize the trial-related arbitrator, inspector, and ethics committee for direct access to the original medical record for verification of test procedures or test data. The information will be kept confidential.
According to the specific circumstances, the costs of surgery, postoperative rehabilitation, and follow-up will be derated. The costs will be covered by the research team.
The information, such as trial results and protocols, will be kept confidential. Any data cannot be published unless written authorization is provided by the sponsor.
| Results|| |
Trial status: This trial has been registered in the Chinese Clinical Trial Registry (registration No. ChiCTR-ONC-17010479) on January 19th, 2017. Recruitment of patients is ongoing.
| Discussion|| |
Importance of this study
Decompression can relieve an injured spinal cord, promote blood perfusion, reduce ischemia, and reduce spread of secondary damage. Decompression can also prevent further cell necrosis, preserve residual spinal cord tissue, and promote recovery of nerve function. Therefore, this prospective, multicenter cohort study was designed to observe the effect of dural sac decompression and spinal cord untethering for treating obsolete spinal cord injury. We believe that this study can provide an experimental basis for clinical application of the proposed treatment.
Advantages and limitations of this study
Based on our clinical experience, after treatment with dural sac decompression and spinal cord untethering, nerve function of approximately 1/3 of patients with obsolete spinal cord injury will significantly improve. This will indicate that this treatment has some effect in clinical practice. However, further randomized, controlled, clinical trials are required to examine the time window for decompression and whether to combine drug-assisted therapies.
Evidence for contribution to future studies
This trial is expected to provide an experimental basis for dural sac decompression and spinal cord untethering in patients with obsolete spinal cord injury. This will help to improve survival ability and reduce the social burden.
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All authors participated in the design of the clinical trial, manuscript elaboration and have agreed on the final version of this manuscript.
Conflicts of interest
The protocols have been approved by the Ethics Committee of Chinese PLA General Hospital of China (approval No. S2016-024-01). All protocols will be performed in accordance with the Ethical Principles for Medical Research Involving Human Subjects in the Declaration of Helsinki. The trial will be reported in line with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist.
Declaration of patient consent
The authors certify that they will obtain all appropriate patient consent forms. In the form, the patients will give their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Data sharing statement
No data is reported in the article.
Checked twice by iThenticate.
Externally peer reviewed.
Additional file 1: SPIRIT checklist.
[Table 1], [Table 2]