Predictors of successful treatment after transforaminal epidural steroid injections in patients with lumbar disc herniation

Abstract

BACKGROUND:

Epidural steroid injections are common procedures used to treat lumbosacral radicular pain due to lumbar disc herniation (LDH). It is crucial for the clinician to anticipate which patients can benefit from interventional treatment options.

OBJECTIVE:

This study aimed to examine the effect of radiological and clinical parameters on lumbar transforaminal epidural steroid injections (TFESI)/local anesthetic injection outcomes in patients with LDH.

METHODS:

This study included 286 patients with LDH (146 males and 140 females). All patients received a fluoroscopically guided TFESI (triamcinolone acetonide 40 mg, lidocaine 2%, and 2.5 ml of physiological saline). Patients were evaluated according to radicular pain, the Oswestry Disability Index (ODI) and the Hospital Anxiety and Depression Scale at baseline and 3 months after the injections. Demographic, clinical and magnetic resonance imaging (MRI) findings were recorded to assess the predictive factors for TFESI outcomes. Pfirrmann Grades 1 and 2 were classified as low-grade nerve root compression and Grade 3 was classified as highgrade nerve root compression.

RESULTS:

Compared to baseline measurements there were significant improvements in radicular pain, ODI score, Laseque angle, and Schober test scores 3 months after injection. Improvements of at least 50% in radicular pain relief and the ODI functionality index were ( $n=$ 214) 82%, ( $n=$ 182) 70% respectively at 3 months. Correlation analyses revealed that a shorter duration of symptoms, lowgrade nerve root compression and foraminal/extraforaminal location on MRI findings were associated with a favorable response.

CONCLUSIONS:

Lowgrade nerve root compression was a predictor of a favorable response to TFESI.

Keywords

Epidural injection lumbar disc herniation MRI imaging treatment response nerve root compression

1. Introduction

Lumbar disc herniation (LDH) is a major health issue that restricts daily life activities and causes considerable medical and economic costs to individuals, families and society. Therefore it is crucial for the clinician to anticipate which patients can benefit from nonsurgical treatment options. Intervertebral disk herniation is a common cause of lumbosacral radiculopathy. Radicular pain caused by inflammation of the affected spinal nerve roots [1, 2, 3, 4]. Nonsurgical treatment options include systemic analgesic drugs, physical therapy and epidural steroid/local anesthetic injections in the lumbar radiculopathy. An image-guided lumbar nerve root injection with corticosteroids and/or local anesthetics is a well-recognized technique for the treatment of LDH [3, 5]. Epidural steroid injections are common procedures used to treat lumbosacral radicular pain due to LDH. Transforaminal epidural steroid injections (TFESI)/local anesthetic injections have been advocated as an alternative to surgical treatment for lumbar radiculopathy caused by LDH [5, 6, 7].

Corticosteroids and local anesthetic agents have beneficial effects in reducing inflammation and membrane stabilization in the nerve root as well as removing cytokines from the epidural space due to the washout effect [6, 7, 8]. There are several approaches to epidural injection techniques, including caudal, interlaminar, and transforaminal. The transforaminal approach requires the smallest dose of medication to reach the epidural space [9, 10, 11, 12, 13]. Related studies have reported that transforaminal injections provide better pain relief in the short and medium terms than caudal and interlaminar injections in patients with radicular pain due to LDH [7, 9, 14, 15, 16, 17, 18, 19].

It has been determined that TFESI can be a suitable treatment option with no pain recurrence for long periods of time in many patients. However TFESI had little therapeutic effect in some patients necessitating surgical intervention. Many clinical and radiological factors can affect the success of TFESI treatment for lumbar radiculopathy [19, 20, 21, 22]. Few studies have investigated the clinical and radiological parameters of LDH that influence TFESI outcomes. Results from existing studies are conflicting [23, 24, 25, 26, 27, 28, 29, 30, 31, 32]. Some studies [20, 21, 30] have shown that high-grade nerve root compression detected on MRI is the key predictor of poor recovery. On the contrary, it has been concluded that high-grade nerve root compression has no effect on recovery [32]; moreover, it has positively influenced recovery [23, 26] in other studies. In the majority of previous studies, a correlation was found between short symptom duration and treatment success [8, 22, 30, 32]. In some of these studies, correlation analysis was performed, and it was observed that symptom duration had no predictive value in relation to improvement [22, 32]. However, some studies have found no relationship between symptom duration and treatment response [21, 27]. The aim of this study is to determine the effect of radiological and clinical parameters on lumbar TFESI outcomes in patients with lumbar radiculopathy due to the LDH.

2. Methods

2.1 Patient characteristics

Between May 2019 and October 2022, 286 patients who were diagnosed with LDH underwent lumbar TFESI at the Yardımeden Physical Medicine and Rehabilitation Department and were enrolled in this prospective study. The participants age range were 18–68 years, having body mass index (BMI) of $<$ 40 and had radicular leg pain with positive straight leg raise test (30–70 degrees) and Laseque sign with or without low-back pain. The inclusion criteria were: unilateral leg pain due to the lumbar radiculopathy, correspondence of MRI findings of LDH with clinical manifestation, history of failure to conservative treatments. The diagnosis of LDH and the level of TFESI was based on the magnetic resonance imaging (MRI) and physical examination findings, and all patients had monosegmental dermotomal pain distribution at L4, L5 or S1 root levels. The exclusion criteria were: Patients who underwent lumbar disc surgery had non-concordant pain based on MRI findings, neurologic deficits or progressive muscle weakness, bladder/bowel disturbances, spondylolysis or spondylolisthesis, central canal stenosis, former lowback surgery, grade 0 hernias according to Pfirmann and Lee grading system, malignancies, inflammatory rheumatic diseases (such as spondyloarthritis, rheumatoid arthritis), and spinal infection; those with coagulopathy or a previous allergic reaction to local anesthetics. Additional patient data, including age, gender, duration of symptoms, and injection level were recorded. All patients were informed of the study and injection protocol and consented to participate. This study was approved by the local ethics committee of Dicle University Medical School (approval number: 364 (17.10.2014)).

Psychological status was measured using the Hospital Anxiety and Depression Scale (HADS) [33, 34]. HADS is a Likert-type selfevaluation scale that consists of 14 items: 7 to investigate depression symptoms (HADS-D) and 7 to investigate anxiety symptoms (HADS-A). Higher scores indicate poor psychological status.

2.2 Measurement of the clinical data and pain score

Figure 1.

Epidural contrast spread patterns under fluoroscopy guidance during transforaminal epidural injections. (a) L4 nerve root, (b) L5 nerve root, (c) S1 nerve root.

All clinical data were recorded at baseline and 3 months after the injection. Pain scores (lumbar/radicular pain) were recorded using a 10-point visual analog scale (VAS). After the first injection patients with a pain improvement of less than 50% according to the VAS were considered inadequate pain relief. At the 2-week follow-up, the TFESI procedure was repeated in patients with inadequate pain relief. No additional intervention was performed during the 3-month period. At 3-month follow-up, a reduction in the VAS score of 50% or more was accepted as a recovering group, 50% or less was non-recovering group. Percentage reduction in the VAS was accepted as a primary outcome. Analyses were performed to identify possible predictive factors on lumbar TFESI outcomes in patients with LDH. Measurements of finger-tofloor distance with the patient in fully tolerated hip flexion and findings of the modified Schober test were recorded. The Oswestry Disability Index (ODI) questionnaire was completed at the same time points. Patients scores between zero and five, where zero indicated “normal” and five indicated “complete impairment”. The total scores could range from 0 to 100 [35, 36].

2.3 Radiological assessment

Morphology and location (central, subarticular/paracentral, foraminal and extraforaminal) of disc herniation was categorized using the classification system of Fardon and Milette [37, 38] in terms of bulging; disc material overlaps the vertebral body endplates between 50% and 100% of the circumference, protrusion broad-based herniation which involves 25–50 % of axial disc/vertebral body endplate circumference, extrusion in at least one plane, any one distance between the edges of the disc material beyond the disc space is greater than the distance between the edges of the base in the same plane, sequestration the displaced disc material has lost all continuity with the disc body [26, 37].

The grading system of Pfirrmann et al. [39] was used to assess the severity of nerve root compression in paracentral discal herniation. The grade of nerve compression was assessed on axial T2-weighted images and sagittal T1-weighted images. Accordingly, Grade 0 (normal) indicates that there is no contact between the disc material and nerve root and that the epidural fat layer between the nerve root and disc material is preserved. Grade 1 (contact) indicates that there is visible contact between the disc material and nerve root, no epidural fat layer is visible between the nerve root and disk material and the nerve root is in the normal position and not dorsally deviated. Grade 2 (deviation) indicates dorsal deviation of the nerve root. Grade 3 (compression) indicates compression of the nerve root between the disc material and the wall of the spinal canal. Grades 1 and 2 are classified as low-grade nerve root compression, whereas Grade 3 is classified as high-grade nerve root compression.

In cases of foraminal DH, the severity of NR compression was analyzed in the sagittal plane and classified according to Lee et al. [40]. Grade 0, no foraminal stenosis. Grade 1 (mild), Narrowing of perineural fat in two opposing directions (vertical or transverse). Contact of disc material with the superior to inferior or the anterior to posterior direction of the nerve root. Grade 2 (moderate), obliteration of perineural fat in all four directions without morphologic changes in both vertical and transverse directions. Grade 3 (severe), collapse or morphologic change of nerve root. Grades 1 and 2 are classified as low-grade nerve root compression, whereas Grade 3 is classified as high-grade nerve root compression. Magnetic resonance images were analyzed by an experienced radiologist (author S.H.) who used previously published classification systems. The radiologist was blind to all clinical information. TFESI levels were determined according to the MRI findings.

2.4 Treatment procedure

All patients received the same injection technique. TFESIs were administered under fluoroscopic guidance and strict aseptic conditions. A single fluoroscopy C-arm system (Ziehm Vista Imaging Systems, Germany, 2008) was used and all procedures were performed by the same physiatrist (experienced in more than 30,000 TFESI procedures) at the interventional pain unit of a secondary medical center in order to eliminate variability in outcomes related to interphysician technique differences. Patients were placed in the prone position with a pillow under the lower abdomen to minimize lumbar lordosis on the fluoroscopy table. The skin under and around the site marked for injection was prepared and draped under aseptic conditions. The soft tissue was anesthetized using 2 mL of 1% lidocaine. TFESIs were administered using 22G, (3.5–5 inches) short beveled spinal needles. Anatomical regions were identified. The needle was advanced and inserted into the area beneath the pedicle. As the needle was advanced, anteroposterior and lateral views were obtained to confirm the correct needle positioning. To confirm the epidural space and the lack of intravascular contrast flow, 0.5–1 mL of Iohexol was injected (Fig. 1). After confirmation, 1.5 mL of triamcinolone acetonide 40 mg, 2 mL of 2% lidocaine and 2.5 mL of physiological saline (total of 6 mL) were injected. The patients were observed for 3 hours after the injection. No major complications such as nerve damage, constant hemorrhage, or infection were observed.

2.5 Statistical analysis

The calculations were carried out using the Statistical Package for Social Sciences software version 26.0 for Windows (SPSS Inc., Chicago, IL, USA). Descriptive data were expressed in mean $\pm$ standard deviation, or number and frequency. The Kolmogorov–Smirnov and Shapiro–Wilk tests were used to analyze normally distributed variables, while nonparametric tests were used to analyze non-normally distributed variables. The continuity correction chi-square test or Fisher’s exact test was used to analyze categorical data. The Student $t$ -test (paired samples $t$ -test) was used to evaluate the pre- and post-TFESI application differences within the groups. The comparison of the data between the recovering/non-recovering groups was conducted using the independent samples $t$ -test. Correlations between different continuous variables were evaluated by Pearson’s or Spearman’s correlation analyses depending on the distribution of the variables. Factors with a $p$ -value of $<$ 0.05 in univariate analysis were included in the multivariate binary logistic regression analysis. A multivariate analysis was performed using a binary logistic regression analysis to determine the independent predictors of successful treatment in the pain score as well as the effects of confounding factors among potentially independent predictors. A forward stepwise method was used to construct multivariate logistic regression models in relation to various dependent variables. A $p$ -value $<$ 0.05 and a 95% confidence interval were considered statistically significant.

3. Results

Table 1
Clinical and demographic characteristics of the patients with LDH (mean $\pm$ SD or %)

Patient characteristics	Mean $\pm$ SD ( $n$ , %)
Age	43.39 $\pm$ 12.39
BMI	28.21 $\pm$ 4.55
Sex (m/f, %)	53/47
Disc location
Median/paramedian	244 (93.8%)
Foraminal/far lateral	16 (6.2%)
Disc morphology
Protrusion	114 (43.8%)
Extrusion	142 (54.6%)
Sequestration	4 (1.5%)
Paracentral nerve root compression ( $n=$ 244)
Pfirrmann grade 1	40 (16.4%)
Pfirrmann grade 2	151 (61.8%)
Pfirrmann grade 3	53 (21.7%)
Foraminal nerve root compression ( $n=$ 16)
Lee grade 1	2 (12.5%)
Lee grade 2	9 (56.2%)
Lee grade 3	5 (31.2%)
Injection levels
L4	17 (6.5%)
L5	138 (53.1%)
S1	105 (40.4%)

BMI: body mass index; m: male; f: female.

Table 2

Disease related characteristics of Favorable/non favorable patients

Patient characteristics	Recovering responders ( $n=$ 46)	Non recovering responders $n=$ 46	$p$
Age	44.14 $\pm$ 9.23	43.41 $\pm$ 10.55	0.736
BMI	28.72 $\pm$ 4.45	28.47 $\pm$ 5.22	0.714
Symptom duration	16.27 $\pm$ 9.45	26.80 $\pm$ 11.65	0.009
Pain change score ^VAS	69.35 $\pm$ 15.67	22.85 $\pm$ 9.25	$<$ 0.001
ODI change score	41.29 $\pm$ 8.07	14.87 $\pm$ 5.57	$<$ 0.001
Disc morphology
Protrusion	99 (46.2%)	15 (32.6%)	0.234
Extrusion	112 (52.3%)	30 (65.2%)
Sequestration	3 (1.5%)	1 (2.1%)
Disc location
Median/paramedian	199 (92.9%)	45 (97.8%)	0.084
Foraminal/far-lateral	15 (7.8%)	1 (2.2%)
Median/Paramedian nerve root compression ( $n=$ 244)
Pfirrmann gr 1	40 (16.4%)	0
Pfirrmann gr 2	145 (59.4%)	6 (15.2%)	$<$ 0.001
Pfirrmann gr 3	14 (5.7%)	39 (84.8%)
Foraminal/far lateral nerve root compression ( $n=$ 16)
Lee gr 1–2	11 (68%)	0	0.312
Lee gr 3	4 (32%)	1 (100%)
Laseque test change score ^angle	40.43 $\pm$ 9.88	21.86 $\pm$ 4.09	$<$ 0.001
Schober test change score ^cm	1.45 $\pm$ 0.76	0.78 $\pm$ 0.34	$<$ 0.001
Muscle weakness	57 (26.6%)	17 (36.4%)	0.207
HADS depression	5.93 $\pm$ 0.42	6.02 $\pm$ 0.54	0.412
HADS anxiety	6.43 $\pm$ 0.38	6.87 $\pm$ 0.81	0.359

BMI: body mass index, ODI: Oswestry disability index, HADS: hospital axiety and depression scale.

Table 3

Final logistic regression model; Pfirrmann scale as dependent variable (nerve root compression grade 1–2 vs grade 3)

	B	SE	Wald	$p$	OR
Nerve root compression	$-$ 4.377	0.495	78.217	$<$ 0.001	0.013
Constant	1.025	0.312	10.813	0.001	2.786

A total of 286 patients diagnosed with LDH underwent the TFESI procedure. No major complications such as nerve damage, constant hemorrhage or infection were observed. At the 2-week followup, the TFESI procedure was repeated for 68 patients because of inadequate pain relief. At the 3-month follow-up, 26 patients were excluded from the study because they had undergone surgery. The majority of the patients were males (53%). The mean age was 43.39 $\pm$ 12.39 years. The mean duration of symptoms was 19.89 $\pm$ 5.22 weeks. The levels of injections were determined as L4 root in 17 (6.5%) patients, L5 root in 138 (53.1%) patients and S1 root in 105 (40.4%) patients. The demographic and diseaserelated characteristics of the patients are listed in Table 1. Compared to baseline measurements there were significant improvements in radicular pain, the ODI score, the Laseque angle and the Schober test scores 3 months after the injection. The characteristics of recovering and non-recovering patients are listed in Table 2. Improvements of at least 50% in radicular pain relief and the ODI functionality index were 82% ( $n=$ 214), 70% ( $n=$ 182) respectively at 3 months.

Correlation analyses revealed that shorter duration of symptoms, lowgrade nerve root compression and foraminal/extraforaminal location on MRI findings were associated with a favorable response. The multivariate logistic regression analysis revealed that only lowergrade nerve root compression was a predictor of a favorable response to TFESI (Table 3).

4. Discussion

Previous studies [1, 2, 3, 5, 20, 21] have shown that TFESI relieves pain and improves functional status in patients with LDH. In this study, 82% of our patients who underwent TFESI experienced pain relief and 70% noticed an improvement in their functional status Our findings suggest that the major factor in the healing of LDH was not the morphological size of the hernia but the grade of nerve root compression. Patients with Pfirrmann Grade 3 on MRI had lower recovery (pain and functional status) scores than patients with Grades 1 and 2. The relationship between the radiological extent of lumbar discopathy and patient recovery is difficult to establish. Some studies [20, 21, 30] have shown that highgrade nerve root compression detected on MRI is the key predictor of poor recovery, which is consistent with our data. On the contrary, it has been concluded that highgrade nerve root compression has no effect on recovery [32, 41, 42]; moreover it has positively influenced recovery [23, 26] in other studies. However, in these studies, Pfirrmann Grades 0 and 1 were accepted as low grades and Pfirrmann Grades 2–3 were accepted as high grades. In our statistical analysis, we classified stages 1–2 as low grades and stage 3 as high grades. Studies showing that nerve root compression is not associated with treatment outcomes have reported that radicular pain is associated with neurogenic inflammation rather than mechanical compression of the nerve root [24, 43, 44]. However, it should be noted that neurogenic inflammation in LDH is associated with direct compression of nerve roots. These discrepancies could be attributed to the use of two-dimensional MR images in the diagnosis of LDH. Morphologically, a large hernia may exert less pressure on the nerve root, whereas a small hernia may exert too much pressure on the nerve root. Such overlooked cases can be detected more easily with the widespread use of three-dimensional MRI in the following years. The main complaint in patients with LDH is radicular pain radiating to the leg rather than low back pain. In fact, many patients do not show symptoms until the compression of the nerve root and the first symptom is the sudden onset of leg pain. In the present study, no correlation was found between the morphological size of the herniated material according to the Fardon-Millette classification (bulging, protrusion, extrusion, sequester) and recovery. Although the hernia is large in disc extrusion and sequestred disc, because the annulus fibrosis fibers are completely ruptured, the surplus material content has less annulus fibrosa and more nucleus pulposus As the nucleus pulposus is a softer material, neovascularization and phagocytosis function more effectively in this type of hernia [45, 46, 47]. In addition to these data, transligamentous hernias are recognized as a foreign substance, which results in an increased immune response, leading to increased inflammation and phagocytosis. Accordingly, all these reasons may facilitate the shrinkage of the disc material in extruded and sequestred hernias [26, 48].

Almost all previous studies agreed that TFESI was much more effective in farlateral hernias [21, 24, 26, 49, 50, 51, 52]. In our study, we found that foraminal and extraforaminal hernias had higher recovery rates than paracentral and central hernias, but this result was not statistically significant. This contradictory result may be due to the relatively small number of patients with far-lateral/foraminal hernias. The transforaminal approach improves access to the foraminal area and allows drugs to be injected just around the compressed nerve root. Large hernias may prevent the passage of the drug (steroid/local anesthetic) to the medial nerve root in paracentral hernias. Therefore, farlateral hernias may respond better to TFESI treatment. In addition, in farlateral hernias, the nerve root is not compressed between the vertebral lamina and the disc; there is only disc compression, which may explain why far-lateral hernias heal more easily [21, 24, 26, 49, 50, 51, 52]. Because farlateral hernias respond better to treatment, surgical treatment should not be recommended to the patient until all conservative treatments have been applied and there is loss of muscle strength [24, 26].

In this study, we found no correlation between the patients’ age, body mass index, and gender and their level of improvement. Similarly, previous studies have also reported that body mass index and gender had no effect on treatment outcomes [8, 20, 24, 25, 27]. However, the effect of age on TFESI is a controversial issue. Many studies have found that age does not affect treatment outcomes, which is consistent with our data [20, 22, 25]. However, Lee et al. [24] demonstrated that recovery scores were better in elderly patients than in younger patients; however, because the follow-up period was short in this study, no conclusions about long-term results can be drawn. In contrast to this finding, Ekedahl et al. [30] reported higher effectiveness in treatment outcomes with TFESI in young individuals in a 1-year follow-up study. The authors explained this as prolonged stenosis causing ischemia in the nerve root and decreased inflammatory responses in elderly patients.

In our study and in the majority of previous studies, a correlation was found between short symptom duration and treatment success [8, 22, 30, 32, 41, 53]. In some of these studies, logistic regression analysis was performed and it was observed that symptom duration had no predictive value in relation to improvement [22, 32, 41]. In chronic cases with long symptom duration, recovery may be more limited because further fibrosis and ischemia of nerve fibers develop in the epidural space [8, 22]. However, some studies have found no relationship between symptom duration and treatment response [21, 27].

Previous studies have shown that high anxiety and depression scores negatively affect treatment success [3, 31]. In addition, the presence of depressive symptoms in patients undergoing TFESI was found to be associated with high pain scores, and postoperative recovery levels were also low in the same group of patients [53, 54]. In contrast to these data, Kim et al. [55] reported that TFESI efficacy was not different between the patients with and without depression. In our study, anxiety and depression scores were similar in the recovered and non-recovered patient groups.

Our study was limited by a 3-month follow-up period, which was insufficient for a disease that often has a chronic course, such as LDH. A second limitation is that we excluded elderly patients with lumbar stenosis; therefore, we could not evaluate the recovery patterns of LDH in the elderly patient group. Finally, because the number of our patients with foraminal/farlateral disc herniation was relatively small, we could have more clearly demonstrated the effectiveness of TFESI in this group of patients if our study had a larger sample size with foraminal hernias.

5. Conclusion

The present study demonstrated that TFESI is a practical, safe and effective treatment for LDH. We discovered that recovery in patients undergoing TFESI is associated with high-grade nerve root compression rather than hernia size. We also found that farlateral and foraminal hernias responded better to TFESI than paracentral hernias. Approaching a global health problem such as LDH necessitates identifying the factors involved in recovery, both in terms of treatment costs and the prevention of workforce loss.

Ethics statement

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. All patients were informed of the study and injection protocol and provided written informed consent.

Funding

No financial support was received from any person or institution.

Author contributions

MAS: Performed transforaminal epidural injections, planned the investigation, and wrote the manuscript; IB: Collected patient data and current literature and planned the investigation; SH: Evaluated MRI findings

Footnotes

Conflict of interest

The authors declare that they have no conflict of interest.

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Predictors of successful treatment after transforaminal epidural steroid injections in patients with lumbar disc herniation

Abstract

BACKGROUND:

OBJECTIVE:

METHODS:

RESULTS:

CONCLUSIONS:

Keywords

1. Introduction

2. Methods

2.1 Patient characteristics

2.2 Measurement of the clinical data and pain score

2.4 Treatment procedure

2.5 Statistical analysis

3. Results

Table 1 Clinical and demographic characteristics of the patients with LDH (mean ± SD or %)

5. Conclusion

Ethics statement

Funding

Author contributions

Footnotes

Conflict of interest

References

Table 1
Clinical and demographic characteristics of the patients with LDH (mean $\pm$ SD or %)