Using Inflammatory Biomarkers and EMG Results to Predict Epidural Injection Response in Patients Diagnosed With Lumbar Stenosis
Phase: NA
Conditions: Lumbar Spinal Stenosis
Sponsor: Dallas VA Medical Center

Using Inflammatory Biomarkers and EMO results to Predict 
Epidural Injection Response in Patients Diagnosed with
Lumbar Stenosis
Clinical Study Protocol 
NTC Number: 03511053 
Principal Investigator: Thiru Annaswamy, M.D. 
VA North Texas Healthcare System 
4500 S Lancaster Road 
Dallas, TX 75216 
214-857-0273
01 May 2017 

TITLE / MAIN QUESTION 
Do inflammatory biomarkers and needle electromyography (EMG) findings have independent 
predictive ability to identify patients with lumbar spinal stenosis and neurogenic claudication 
who are more likely to benefit from epidural steroid injections?  
BACKGROUND & SIGNIFICANCE 
Lumbar spinal stenosis is a common cause of back pain and mobility impairment in older adults 
[1]. It is often a multifactorial condition resulting from degenerative changes in the spine, and 
may result in severe disability, with symptoms of lower back pain and/or pain, numbness and 
weakness of the lower extremities that are often exacerbated by walking and/or standing [2]. 
Since lumbar spinal stenosis mostly stems from slowly progressive degenerative changes, 
symptoms often worsen over time, leading to poor health outcomes and high rates of healthcare 
utilization.  
Epidural steroid injection (ESI) with anti-inflammatory compounds such as glucocorticoids is 
commonly provided to alleviate pain from neurogenic claudication in spinal stenosis: it is 
estimated that 25% of ESIs performed in the Medicare population and 74% of ESIs in the 
Veterans Affairs system are for spinal stenosis [3,4]. However, one recent, large, multi-center, 
randomized controlled trial (RCT) demonstrated no significant benefit of epidural corticosteroids 
in alleviating symptoms of spinal stenosis [2]. In this study, Friedly et al. conducted a 
doubleblind, RCT comparing patient outcomes with epidural injection of glucocorticoid plus 
anesthetic (lidocaine) vs. anesthetic (lidocaine) only [5]. They observed no significant 
differences at 6 weeks between the two groups of patients with respect to pain-related functional 
disability or pain intensity. However, a subset of patients who received glucocorticoids plus 
lidocaine reported significantly higher treatment satisfaction and higher reductions in depressive 
symptoms [6]. This suggests that ESIs may be effective for a subset of patients with spinal 
stenosis.   
Another treatment modality for spinal stenosis is decompression surgery, which may be effective 
for some patients but is associated with higher risk especially in the elderly and patients with 
multiple medical comorbidities. In Davis et al.’s observational study, in a two-year period with 
68 patients, 32% of patients opted for surgery, 44% of patients were satisfied with non-surgical 
management and were discharged after 2 years, but the remaining 24% with non-surgical 
management (some of whom chose to decline surgery) did not seem to be satisfied with 
treatment [7]. This study indicates the potential key role that non-surgical management options 
such as ESIs may play, in some patients. However, better patient selection using indicators or 
biomarkers for patients who may most likely benefit from ESIs and other non-surgical treatments 
would be extremely beneficial.  
In studying bio-markers that may predict patients’ response to ESIs, Scuderi et al. found 
interferon-gamma (IG) levels to have high predictive value for patients with lumbar nerve root 
irritation [8], while Golish et al. and Smith et al. found fibronectin-aggrecan complex (FAC) 
levels to have high predictive value for patients with herniated nucleus pulposus (HNP) [9, 10]. 

In addition, many other factors (such as lower age and higher education) have been found to 
predict better outcome for radiculopathy [11]. In particular, needle electromyography (EMG) has 
been shown in several studies to be a strong predictor for response to lumbar epidural steroid 
injection (LESI) and transforaminal epidural steroid injection (TFESI) for patients with 
lumbosacral radiculopathy (LSR) [12-14]. Inspired by these studies, we would like to explore if 
certain bio-markers such as IG & FAC along with EMG findings can help us predict which 
patients with spinal stenosis and neurogenic claudication will optimally benefit from ESIs.  
  
METHODS  
  
Subject Recruitment: Recruit 10 adults (who can read English and complete assessment 
instruments) referred to the UT Southwestern Spine Clinic aged 18 years or older with 
mildsevere lumbar central canal stenosis identified by Magnetic Resonance Imaging (MRI) or 
Computerized Tomography (CT) scan, who have symptoms consistent with neurogenic 
claudication such as pain, weakness, and/or numbness triggered by standing or walking and 
relieved by sitting. Exclude patients with cognitive impairment; clinical co-morbidities 
interfering with data collection; severe vascular, pulmonary, or coronary artery disease that limits 
ambulation; spinal instability requiring surgical fusion; severe osteoporosis; metastatic cancer; 
excessive alcohol consumption or evidence of non-prescribed or illegal drug use; pregnancy; 
concordant pain with internal rotation of the hip; active local or systemic infection; abnormal 
coagulation; allergy to local anesthetic, steroid, or contrast; previous lumbar spine surgery; 
prisoners; epidural steroid injection within previous 6 months; rheumatologic disorders such as 
rheumatoid arthritis, psoriatic arthritis, and systemic lupus erythematosus.  
  
Study procedures: Once enrolled, all of the patients will undergo routine sensory and motor 
nerve conduction studies with EMG and blood tests. Afterwards patients will be scheduled to 
undergo an ESI of steroid (dexamethasone) under fluoroscopic guidance at or below the level of 
the suspected pathology. Prior to the injection, a maximum of 3 ml of normal saline will be 
injected into the epidural space, and aspirated shortly thereafter, and sent for specified 
inflammatory laboratory tests. The ESI will then take place as per standard procedure.  
Independent clinical variables will be assessed at three time points including at the initial visit, at 
1 month, and 2 months after the ESI. Additional measures used will include the pain disability 
questionnaire (PDQ), the Swiss Spinal Stenosis Questionnaire, and Numerical Rating Scale 
(NRS) for back and leg pain.  
  
Lab Collections for Inflammatory Lab Tests: Complete blood count, High sensitivity CRPs 
(hsCRPs).  Bio-Plex Pro Human Cytokine 27-plex Assay, 1x96:  coupled magnetic beads, 
detection antibodies, standards, assay buffer, wash buffer, detection antibody diluent, 
streptavidin-PE, filter plate, sealing tape, standard diluent, sample diluent for the detection of IL-
1beta, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p70), IL-13, IL-15, IL-17, 
eotaxin, basic FGF, G-CSF, GM-CSF, IFN-gamma, IP-10, MCP-1 (MCAF), MIP-1alpha, MIP-
1beta, PDGFBB, RANTES, TNF-alpha, VEGF.  
  

SPECIFIC AIMS & HYPOTHESES  
  
Specific Aim 1: Identify biomarkers that can predict if patients will experience significant pain 
relief and/or improvement of quality of life following ESI, defined as minimum of 30% 
improvement in pain and/or PDQ scores.  
  
Hypothesis 1: Since steroids relieve pain mainly through anti-inflammatory effects, patients who 
have pain caused by inflammation, should have certain associated inflammatory biomarkers in 
high concentration, which will predict their response to the steroid injection resulting in 
significant pain relief. Patients who have pain not associated with inflammation, as indicated by 
biomarker levels will therefore not experience significant pain relief after steroid injections.  
  
Therefore, we hypothesize that patients, who have high levels of specific biomarkers identified in 
their blood or epidural aspirate, will respond favorably to an ESI and experience significant pain 
and functional improvement following the ESI.  
  
Specific Aim 2: Identify EMG findings of acute denervation that can predict pain relief from 
ESI.  
  
Hypothesis 2: EMG findings of acute denervation in leg and/or paraspinal muscles are 
indicators/markers of abnormal neural activities associated with pain and inflammation, and 
hence will predict pain and functional improvement from ESI in patients with such EMG 
findings.   
  
Therefore, we hypothesize that patients, who have EMG findings of acute denervation in leg 
and/or paraspinal muscles, will experience significant pain and functional improvement 
following the ESI.  
  
ANALYSIS PLAN: This pilot study of 10 patients will yield preliminary data that will lead to 
standardizing methods of data collection and inform us for a future RCT that is being planned to 
follow soon after.  
  
EXPECTED RESULTS AND RATIONALE:  
 Findings from this pilot study, and data on specific biomarkers including blood tests, epidural 
aspirate analysis and EMG findings that can predict patients’ response to ESI will provide us with 
preliminary data to inform a fully powered clinical trial. Thus informed, this future RCT will be 
designed to scientifically evaluate patients’ long-term response to ESI, determine appropriate 
attribution to epidural steroids, and refine our understanding of the predictive capabilities of 
biomarkers including blood tests, epidural aspirate analysis and EMG findings that can be 
optimally used for better selection for ESI in patients with lumbar spinal stenosis with neurogenic 
claudication. Eventually, similar studies like this that seek to find biomarkers to predict steroid 
effects on health management for a wide spectrum of human pathologies will help clinicians use 

steroids more selectively and effectively, and hence reduce healthcare utilization and unnecessary 
patient care, while optimizing their pain and function.  
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1. Harrast MA: Epidural steroid injections for lumbar spinal stenosis. Curr Rev 
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protocol-Lumbar Epidural steroid injections for Spinal Stenosis (LESS): A double-blind 
randomized controlled trial of epidural steroid injections for lumbar spinal stenosis 
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