Guest Discussants: David E. Fish, MD, James P. Behr, MD, Matthew Smuck, MD
SpineLine Section Editor: Heidi Prather, DO

Case Presentation
A 42-year-old right-handed male police officer presents with a nine-week history of neck, right shoulder and arm pain. He has not noticed changes in gait or balance, bowel or bladder funtion, or strength. His pain increases when he  looks up or rotates right. He has missed several days of work and is unable to sleep at night because of pain. Previous treatment included narcotics and anti-inflammatory medication. On physical examination, he reports pain on palpation of the cervical paraspinals. The neurological exam for muscle strength, muscle stretch reflexes and  sensation is normal. Spurling’s and adverse neural tension signs reproduce the patient’s symptoms into the arm along the biceps and into the wrist, thumb and index finger.

You recommend physical therapy and order an MRI, shown here. The axial (below) and sagittal (right) images demonstrate a right para central C5-6 disc protrusion. You consider offering a cervical injection. What are the pros and cons of that consideration and what type of injection would you recommend?

David Fish, MD, and James Behr, MD, Respond
This 42-year-old man presents with a nine-week history of cervical radicular symptoms and concordant findings of a C5-6 paracentral disc protrusion. So far he has not responded to limited conservative treatment including opioid and anti-inflammatory medications. Currently, treatment of cervical radiculopathy is variable. Recommendations consist of analgesics, cervical collar, traction, physical therapy, interlaminar and transforaminal epidural steroid injections, and surgery.1 Moderate evidence supports the efficacy of conservative therapies when compared to placebo. Given the limited evidence of the safety and efficacy of injection therapies, noninvasive management should be exhausted before proceeding.

Epidural steroid injections are the most common interventional pain procedure performed in the United States. The available literature demonstrates moderate evidence that lumbar epidural steroid injections are effective in reducing pain in the short term and improving functional outcomes.2-5 Additionally, there is convincing evidence that all commonly used approaches for lumbar epidural steroid injections including transforaminal,6 caudal and interlaminar are relatively safe with low reported complication rates. This combination of documented efficacy with a high safety margin justifies their frequent use. However, these generalizations of efficacy and safety cannot be extended to cervical transforaminal epidural steroid injections. Cervical injections are most frequently performed as a therapeutic infiltration of steroid with or without a local anesthetic into the epidural space using either a transforaminal or interlaminar approach. Occasionally, selective nerve root blocks (SNRB), in which a small amount of local anesthetic is applied to the dorsal root ganglion, aids surgical planning by gauging pain relief at that level. Despite conflicting evidence of effectiveness, these procedures are commonly used. No well-designed randomized controlled trials confirm efficacy of any cervical epidural steroid injections regardless of the approach or technique used. In 2001, Riew et al5 evaluated the role of cervical SNRB to avoid surgical intervention. There was no difference in surgery rates between the patients undergoing SNRBs with bupivicaine alone or with steroid.

Both cervical epidural steroid injections and SNRBs confer a significant risk of potentially devastating complications. Derby et al7 described the experience of 17 of 29 International Spine Intervention Society instructors who responded to a retrospective survey. The report included a total of 5,968 cervical epidural steroid injections. In the interlaminar group, 23 minor complications were reported in 4,389 consecutive injections. In the transforaminal group, there were five minor complications in 1,579 injections (0.32%).There were no serious complications in either group. The study’s retrospective nature likely underestimated the true incidence of complications. The reported safety of these procedures must be considered with caution.

In 2003, Botwin et al8 reviewed the charts of 157 patients who received 345 interlaminar epidural steroid injections and reported complications without resulting significant morbidity or mortality in 16.8%. Twenty-three (6.7%) patients reported increased neck pain; 16 (4.6%) reported transient nonpositional headaches that resolved within 24 hours; six patients (1.7%) reported insomnia the night of the injection; six patients (1.7%) vasovagal reactions; five patients (1.5%) facial flushing; one patient (0.3%) fever the night of the procedure; and one patient (0.3%) dural puncture. These side effects and complications were all self limited and did not differ substantially from those seen in lumbar epidural steroid injections.

Contrary to these studies, a growing body of literature reports serious complications including central nervous system
injury. The exact number of events is unknown. Scanlon et al9 reported a total of 78 cases including 30 cases of brain or spinal cord infarction, 16 vertebrobasilar brain infarcts, 12 cervical spinal cord infarcts, and two combined brain and cervical spinal cord infarcts. The brain infarcts invariably involved the cerebellum, brainstem or posterior cerebral artery territory. The extent of infarct ranged from unilateral cerebellar infarct to extensive right hemisphere and thalamic infarct in the posterior cerebral artery distribution. Another case resulted in bilateral “top of the basilar” syndrome following injection of methylprednisolone and lidocaine. The remaining 24 neurologic complications included five deaths from unknown causes, three cases of high spinal anesthesia, three cases of transient ischemic attack, two seizures, two cases of spinal cord edema, one case of brainstem edema with herniation, one case of brain edema with reversible ischemic neurologic deficit (RIND), one case of cortical blindness due to air embolus, one case of cervical epidural hematoma, one case of paraspinal hematoma, one case of peripheral neurapraxia and one case of vasovagal response. The majority of these cases are thought to result from a combination of the transforaminal approach with the dense cervical spinal vascular network. Aspiration prior to injection is inadequate to prevent intravascular injection. Furman et al10 demonstrated that 19.4% of fluoroscopically guided cervical injections resulted in vascular spread despite negative aspiration.

The injection of particulate steroids into vulnerable arteries with the transforaminal approach is the likely cause of many of these devastating complications. As a result, many practitioners use only the interlaminar approach. Others perform digital subtraction angiography and injecting non-particulate steroids with the transforaminal approach. While these measures appear to improve the relative safety of cervical epidural steroid injections, no single well-designed study compares the efficacy of the interlaminar approach compared to the transforaminal approach. No studies confirm improved safety conferred by either digital subtraction angiography or of nonparticulate steroid injection. Limited evidence suggests that interlaminar injections in the lumbar spine are less efficacious than transforaminal injections. 11 Finally, nonparticulate steroid may be less effective than particulate steroid.12

More research is needed to clearly demonstrate the effectiveness and safety of cervical epidural steroid injections. At
this time, no convincing evidence supports their efficacy and disastrous complications have occurred. Until studies confirm effectiveness and safety, these procedures should be performed by experienced practitioners only after all other conservative options have been explored. If performed, an interlaminar approach or digital subtraction angiography and nonparticulate steroid with the transforaminal approach should be employed.

References
1. Carette S, Fehlings MG. Clinical practice. Cervical radiculopathy. N Engl J Med. 2005;353(4):392-399.

2. DePalma MJ, Bhargava A, Slipman CW. A critical appraisal of the evidence for selective nerve root injection in the treatment of lumbosacral radiculopathy. Arch Phys Med Rehabil. 2005;86(7):1477-1483.

3. Abdi S, Datta S, Trescot AM, et al. Epidural steroids in the management of chronic spinal pain: a systematic review. Pain Physician. 2007;10(1):185-212.

4. Carette S, Leclaire R, Marcoux S, et al. Epidural corticosteroid injections for sciatica due to herniated nucleus pulposus. N Engl J Med. 1997;336(23):1634-1640.

5. Riew KD, Yin Y, Gilula L, et al. The effect of nerve-root injections on the need for operative treatment of lumbar radicular pain. A prospective, randomized, controlled, double-blind study. J Bone Joint Surg Am. 2000 Nov;82-A(11):1589-93

6. Botwin KP, Gruber RD, Bouchlas CG, et al. Complications of fluoroscopically guided transforaminal lumbar epidural injections. Ach Phys Med Rehabil. 2001;81(8):1045-1050.

7. Derby R, Lee SH, Kim BJ, Chen Y, Seo KS. Complications following cervical epidural steroid injections by expert interventionalists in 2003. Pain Physician. 2004;7(4):445-449.

8. Botwin KP, Castellanos R, Rao S, et al. Complications of fluoroscopically guided interlaminar cervical epidural injections. Arch Phys Med Rehabil. 2003 May;84(5):627-633.

9. Scanlon GC, Moeller-Bertram T, Romanowsky SM, Wallace MS. Cervical transforaminal epidural steroid injections: more dangerous than we think? Spine. 2007;32(11):1249-1256.

10. Furman MB, Giovanniello MT, O’Brien EM. Incidence of intravascular penetration in transforaminal cervical epidural steroid injections. Spine. 2003;28(1):21-25.

11. Schaufele MK, Hatch L, Jones W. Interlaminar versus transforaminal epidural injections for the treatment of symptomatic lumbar intervertebral disc herniations. Pain Physician. 2006;9(4):361-366.

12. Stanczak J, Blankenbaker DG, De Smet AA, Fine J. Efficacy of epidural injections of Kenalog and Celestone in the treatment of lower back pain. AJR AM J Roentogenol. 2003;181(5):1255-1258.

Matthew Smuck, MD, Responds
This patient has symptoms of a right C6 radiculopathy. The positive Spurling test confirms the diagnosis as it has high specificity for cervical radiculopathy1 and subsequent imaging reveals a corresponding C5-6 disc protrusion. Despite the frequency of intervertebral disc herniations, controversies continue regarding optimal managment as the discussion illustrates.

In the nine weeks since his symptoms began, this policeman has received limited conservative treatment. The natural history of cervical radiculopathy is favorable. He lacks reflex and motor deficits on examination. I would encourage continuation of the conservative treatment plan, proceeding with the recommended physical therapy, adjusting his activities and medications as needed and frequent follow-up over the coming weeks to monitor his condition. Should he fail to improve, more invasive treatments would then be recommended. For purposes of this discussion, I will assume that he did not respond to the above treatments. Failure of conservative care in this setting is a relative indication for invasive treatment such as injections or surgery. Therefore, I recommend proceeding with a cervical epidural injection.

Because the terminology surrounding these injections is often interchanged, I will provide a brief description of the most common types of injections used in patients with cervical radiculopathy to inform the following discussion. Two approaches are used for epidural delivery of medications to the cervical spine, namely interlaminar and transforaminal. An interlaminar epidural (sometimes called “translaminar”) is a therapeutic injection of corticosteroids with or without local anesthetic placed from a posterior approach between the lamina. A transforaminal epidural is also a therapeutic injection of corticosteroids with or without local anesthetic placed from an anterolateral approach into the neuroforamen with confirmation of contrast spread medial to the pedicle and into the epidural space. Finally, selective nerve root blocks (often this terminology is incorrectly used to describe transforaminal epidural injections) are done with diagnostic intentions and utilize only a local anesthetic with confirmation of contrast spread to the dorsal root ganglion (DRG) but not more proximally into the epidural space. In a selective nerve root block, the amount of anesthetic injected is determined in part by the amount of contrast needed to spread to the DRG and does not typically exceed 1cc.

Compared to lumbar radiculopathy, cervical radiculopathy treatments are poorly researched and thus more controversial. In the lumbar spine, evidence suggests that epidural injections are sufficiently safe and are effective in reducing pain and need for surgery. In addition, randomized controlled trials demonstrate that outcomes of transforaminal epidural injections are a superior to interlaminar epidural injections.2,3 While I agree with my colleagues that these findings do not directly translate into treatment of cervical radiculopathy, I do think that they can inform our current choice of treatments as the biochemical insult caused by herniation of nucleus pulposus is the same in the cervical spine as it is in the lumbar spine. In practice, I find that cervical epidural injections are as helpful as lumbar injections in patients with radiculopathy.

Currently, the efficacy of cervical epidural injections, both interlaminar and transforaminal, remains unknown because neither has been randomized against placebo. Although the evidence is limited, it is not completely lacking. Multiple prospective studies have demonstrated their effectiveness in reducing pain and the need for surgery.4-6 In fact, in one study, the majority of patients reported recovery after a single injection.6 The primary objective of nonsurgical treatment of acute radicular pain is to ameliorate the symptoms and restore function while the favorable natural history runs its course. For this purpose, epidural corticosteroids have proven beneficial. Therefore, an epidural steroid injection is the best treatment option for this patient with potential to reduce his pain and increase his function while avoiding the risks of surgery.

What Injection is Best? My preference would be a right C5-6 transforaminal epidural injection. The goal of a therapeutic injection is to deliver a single dose of a potent corticosteroid to the site of pathology. In this case, a right C5-6 transforaminal injection is the most direct and selective route toward the observed disc protrusion. Theoretically, a concentrated deposition of steroid at this site may produce better results. An interlaminar injection at C5-6 is ill advised given the small size of the posterior epidural space here, so an injection at C7-T1 is required using the interlaminar technique. From this location, the medications may or may not reach their intended target. In fact, interlaminar epidural injections reach the site of pathology in as few as 26% of patients.7 In direct comparisons, transforaminal epidural injections have proven superior to interlaminar injections.2,3

Not long after the first arguments were proffered on behalf of transforaminal injections, catastrophic complications that can occur were reported.8,9 These reports led some to abandon the procedure. Others continued only after initiating additional safety measures. The relative effectiveness of safety measures such as digital subtraction angiogrpahy for cervical transforaminal epidural steroid injections have not been proven. These studies are impractical if not impossible, in part, because of the extremely low and undefined prevalence of these catastrophic complications. In the two large published case series of cervical transforaminal epidural injections, no serious complications occurred in more than 2,500 injections combined.10,11 An extremely large prospective trial will be required to demonstrate the effectiveness of any single safety method. Also, ethical concerns complicate the establishment of this type of trial. Fortunately, these limitations do not apply to testing the utility of the proposed
safety measures.

Reducing Risks. To understand the methods used to reduce the risks of cervical transforaminal epidural injections, a basic understanding of the mechanisms of injury is required. Serious injuries result from inaccurate needle placement and injection into the spinal cord, needle-induced arterial spasm or dissection, or inadvertent arterial cannulation followed by injection and embolization of particulate corticosteroids.12,8 Although procedural competency is difficult to measure objectively, practitioners must ensure that they have adequate training and experience to perform these potentially dangerous injections.13 Proponents of cervical transforaminal epidural injections have suggested several methods to reduce the incidence of these complications. Three of these methods have been subject to critical investigation of their utility.

Digital subtraction angiography (DSA) is often advocated, but is not one of the three risk reduction methods with a published critical investigation. I have seen preliminary results of two such investigations at national meetings, but their data have yet to be published. So, what three methods have been studied? First, aspiration for blood with a syringe has been shown to have good specificity but low sensitivity (45%).14 Therefore it is useful if positive but not if  negative. Second, using intermittent or static fluoroscopy to identify contrast spread caused a failure in the detection of more than 50% of the inadvertent vascular injections that were observed using live fluoroscopy during contrast injections.15 And third, using dexamethasone, a small particulate corticosteroid, can prevent neurologic injuries even with inadvertent intra-arterial injections.16 Because dexamethasone is not FDA-approved for epidural administration, its use in epidural injections is off-label. Further support for using dexamethasone in cervical transforaminal epidural injections comes from a small prospective randomized trial comparing it to a commonly used large-particulate corticosteroid with no significant differences in outcomes between the two treatment groups.17

In addition to these three risk-reducing practices with known utility, other methods suggested to maximize safety include blunt-tip needles, screening patients for dissection risk factors, minimizing sedation, avoiding needle manipulation after contrast confirmation by injection through extension tubing, and injecting an anesthetic test dose before the corticosteroids.8,9 Some suggest placing the needle tip further lateral in the foramen. However, anatomic dissections have shown that the vulnerable radiculomedullary arteries enlarge going from medial to lateral and are therefore more prone to inadvertent needle cannulation in the more lateral location.18

Other Options. Because the consequences of the serious complication associated with cervical transforaminal epidurals are so dire, it is reasonable to consider the alternatives. Interlaminar epidural injections are a time-honored alternative. Unfortunately, they have never been compared to transforaminal injections in the cervical spine so we know nothing of their relative effectiveness. We do know that they are less effective than transforaminal injections in the lumbar spine. Also, there is no evidence that cervical interlaminar injections are any safer than transforaminal injections. Multiple serious complications have been reported from cervical interlaminar injections including epidural hematoma,19 epidural abscess,20 cervical myelopathy12 and death.21Interlaminar injections are the most common procedure associated with a malpractice claim against a pain physician.

Instead of an epidural injection, another option to consider is systemic corticosteroids. Oral administration is simple and cheap and commonly employed in clinical practice. Here again, data exist to inform treatment in the lumbar spine but not in the cervical spine. Only one published study has investigated use of oral corticosteroids in the treatment of lumbar radiculopathy. In this well-designed randomized placebo controlled trial, oral corticosteroids were no better than placebo.22Several studies of intramuscular steroids for lumbar radiculopathy have also produced negative results. There is only one study of systemic (intramuscular) steroids for cervical radiculopathy, a randomized comparison to cervical interlaminar injections that demonstrated superior results in the latter group.4

Summary
In conclusion, cervical epidural injections are generally safe with a low incidence (0.32% to 1.6%) of minor  complications reported in patients treated by expert hands.10,11 Still, serious morbidity and death have been reported so their use should be carefully considered. In the case presented here, progressing to surgery is premature. Less invasive alternatives should be attempted first and, in my opinion, the potential benefits of cervical injections outweigh the risks. For the reasons outlined above, and given current evidence, I recommend a right C5-6 transforaminal epidural corticosteroid injection. It should be performed by a physician with adequate training and knowledge of all tested and untested methods of reducing the risks of the procedure. Future research will help to determine the exact incidence of serious injury and relative effectiveness between cervical transforaminal and interlaminar epidural injections; work will continue on improving the safety of each technique; and cost/benefit analysis will be performed to inform further our treatment of future patients.


References
1. Tong HC, Haig AJ, Yamakawa K. The Spurling test and cervical radiculopathy. Spine. 2002;27(2):156-159.

2. Schaufele MK, Hatch L, Jones W. Interlaminar versus transforaminal epidural injections for the treatment of symptomatic lumbar intervertebral disc herniations. Pain Physician. 2006;9(4):361-366.

3. Thomas E, Cyteval C, Abiad L, Picot MC, Taorel P, Blotman F. Efficacy of transforaminal versus interspinous corticosteroids injection in discal radiculalgia – a prospective, randomized, double-blind study. Clin Rheumatol. 2003;22(4-5):299-304.

4. Stav A, Ovadia L, Sternberg A, Kaadan M, Weksler N. Cervical epidural steroid injection for cervicobrachialgia. Acta Anaesthesiol Scand. 1993;37(6):562-566.

5. Bush K, Hillier S. Outcome of cervical radiculopathy treated with periradicular/epidural corticosteroid injections: a prospective study with independent clinical review. Eur Spine J. 1996;5:319–325.

6. Vallee JN, Feydy A, Carlier RY, Mutschler C, Mompoint D, Vallee CA. Chronic cervical radiculopathy: lateral approach periradicular corticosteroid injection. Radiology. 2001;218:886–892.

7. Fredman B, Nun MB, Zohar E, et al. Epidural corticosteroids for treating “failed back surgery syndrome”: is fluoroscopy really necessary? Anesth Analg. 1999;88(2):367-372.

8. Tiso RL, Cutler T, Catania JA, Whalen K. Adverse central nervous system sequelae after selective transforaminal block: the role of corticosteroids. Spine J. 2004;4(4):468-474.

9. Scanlon GC, Moeller-Bertram T, Romanowsky SM, Wallace MS. Cervical transforaminal epidural steroid injections: more dangerous than we think? Spine. 2007;32:1249-1256.

10. Derby R, Lee SH, Kim BJ, Chen Y, Seo KS. Complications following cervical epidural steroid injections by expert interventionalists in 2003. Pain Physician. 2004;7(4):445-9.

11. Ma DJ, Gilula LA, Riew KD. Complications of fluoroscopically guided extraforaminal cervical nerve blocks. An analysis of 1036 injections. J Bone Joint Surg Am. 2005;87(5):1025-1030.

12. Bose B. Quadriparesis following cervical epidural steroid injections: case report and review of the literature. Spine J. 2005;5(5):558- 563.

13. Smuck, M, Abbott Z, Zemper E. Interpretation of contrast dispersal patterns by experienced and inexperienced interventionalists. PM&R. 2009;1(1):55-59.

14. Furman MB, Giovanniello MT, O’Brien EM. Incidence of intravascular penetration in transforaminal cervical epidural steroid injections. Spine. 2003;28(1):21-25.

15. Smuck M, Fuller B, Chiodo A, et al. Accuracy of intermittent fluoroscopy to detect intravascular injection during transforaminal epidural injections. Spine. 2008; 33(7):E205-210.

16. Okubadejo GO, Talcott MR, Schmidt RE, et al. Perils of intravascular methylprednisolone injection into the vertebral artery. An animal study. J Bone Joint Surg Am. 2008;90(9):1932-1938.

17. Dreyfuss P, Baker R, Bogduk N. Comparative effectiveness of cervical transforaminal injections with particulate and nonparticulate corticosteroid preparations for cervical radicular pain. Pain Medicine. 2006;7(3):237-242.

18. Huntoon MA. Anatomy of the cervical intervertebral foramina: vulnerable arteries and ischemic neurologic injuries after transforaminal epidural injections. Pain. 2005;117(1-2):104-111.

19. Williams KN, Jackowski A, Evans PJ. Epidural haematoma requiring surgical decompression following repeated cervical epidural steroid injections for chronic pain. Pain. 1990;42:197-199.

20. Huang RC, Shapiro GS, Lim M, Sandhu HS, Lutz GE, Herzog RJ. Cervical epidural abscess after epidural steroid injection. Spine. 2004;29:E7-9.

21. Reitman CA, Watters W, 3rd. Subdural hematoma after cervical epidural steroid injection. Spine. 2002;27:E174-176.

22. Haimovic IC, Beresford HR. Dexamethasone is not superior to placebo for treating lumbosacral radicular pain. Neurology. 1986;36(12):1593-1594.

Disclosures

• DE Fish: e, Allergan, Sanofi-Aventis; k-3, Medtronic, Boston Scientific.
• JP Behr: nothing to disclose.
• M Smuck: c-2, k-2, Arthrocare, Inc. 
  
  

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