Guest Discussants: W. Jeremy Beckworth, MD, Susan Dreyer, MD
SpineLine Section Editor: Heidi Prather, DO

Case Presentation
A 55-year-old, right-handed woman presents with complaints of severe left upper limb pain that has been ongoing for three months. Her pain radiates down the posterior arm and forearm. She does not have progressive weakness, gait dysfunction, loss of dexterity, or bowel or bladder dysfunction. She has been managed with medications and physical
therapy but continues to have severe pain that is functionally limiting.

Physical examination shows full strength in upper limbs but there is a decrease in light touch and pinprick over the dorsum of the third finger. Muscle stretch reflex at the left triceps is decreased compared to the right. Upper motor neuron signs are negative. Neural tension signs reproduce left upper limb pain. MRI is obtained and noted
below. The plan is to proceed with a cervical epidural injection.

Several questions arise when doing this injection. What type of steroid should be used in the epidural injection based on safety and efficacy? Does the approach of a transforaminal versus interlaminar injection make a difference when selecting a steroid? What would be the considerations if this was a lumbar injection?


Figure 1. T2 axial MRI showing foraminal narrowing at the C6-7 level

Jeremy Beckworth, MD and Susan Dreyer, MD, Respond
Particulate steroids have been used in epidural injections for decades. In recent years, embolic events have been reported after transforaminal epidural steroid injections with particulate sterioids. These embolic phenomena have resulted in spinal cord injuries, strokes and deaths.1-5 Undetected vascular injections of the vertebral artery or spinal radicular arteries with particulate steroids are postulated to have caused embolic infarctions.5,6

In cervical transforaminal injections, the vertebral artery should not be encountered if the needle is kept in the posterior
foramen and appropriate needle depth is obtained.7 Conversely, spinal radicular arteries may be encountered even with appropriate needle placement.5 Additionally, detection of intravascular injections into a spinal radicular artery is limited due to the brief flow of contrast in this small caliber vessel. Anatomic studies suggest the location of these radicular arteries may vary within the neural foramen, sometimes with arterial branches in the posterior foramen.8,9 In one case report, a patient developed temporary quadraparesis following the injection of a test dose of local anesthetic despite appropriate needle placement. The injection was aborted and no permanent injuries occurred. The temporary quadriparesis was thought consistent with spinal cord anesthesia in the anterior spinal artery territory.10

Vascular infiltration after cervical transforaminal injections are relatively common. A study of 504 epidurals reported a 19% vascular injection rate.11 It is unclear if any of the vascular injections were arterial in the study. The authors do not specifically state, but the reader suspects, most were primarily intravenous. Either way, their frequency requires that the interventionalist recognize intravascular injections and reposition the needle or abort the procedure.

A survey of pain physicians revealed a total of 78 reported neurologic complications following cervical transforaminal
injections. Among these were: 16 vertebrobasilar brain infarcts, 12 cervical spinal cord infarcts, and two combined brain/spinal cord infarcts. Thirteen cases resulted in death: five with brain infarcts, one with combined brain/spinal cord infarcts, one following high spinal anesthesia, one associated with a seizure and five of unspecified etiology.12

Anatomical studies show that the size of particles in commonly used steroid preparations like triamcinolone (Kenalog), methyprednisolone (Depo-Medrol) and betamethasone (Celestone) equals or exceeds the caliber of many radicular arteries. 13,14 These particulate steroids either are larger in diameter than a red blood cell or tend to form aggregates larger than a red blood cell. In that its particles are smaller and do not aggregate, intravascular injection of dexamethasone should reduce embolic infarct risk.14

Another study compared particulate and nonparticulate steroid injections into the vertebral arteries of pigs under general anesthesia.  Those injected with particulate steroids never regained consciousness.  Subsequent MRIs revealed upper cervical cord and brain stem edema and histologic analysis showed ischemic changes.  The animals injected with nonparticulate steroids did not have ischemic events and recovered without apparent adverse effects.  In the nonparticulate group,  MRIs and subsequent histologic analysis were also normal.15

Thoracic and lumbar transforaminals have similarly been implicated in neurologic complications related to particulate
steroids. Major complications have been attributed to the reinforcing radicular artery of Adamkiewicz.16 This artery typically arises at thoracic levels but it can occur as low as L2 or L3 in about 1% of patients and more rarely at lower levels.17

Paraplegia from transforaminal particulate steroid injections at lumbar levels has been reported in the literature. These cases have been documented at the following levels: L2-3,18 L3-4 in two cases,19 L4-520 and S1.21 After all of these injections, patients developed thoracic paraplegia and most cases reported signal intensity changes within the lower thoracic cord on MRI. This suggests a vascular communication with the arterial supply to the lower thoracic cord. Although quite rare, even lumbosacral injections could precipitate significant complications.

Efficacy of Steroids in Epidural Injections
Very little data compare the clinical efficacy of particulate versus nonparticulate steroids. In 2006, Dreyfuss21 compared the efficacy of dexamethasone to triamcinalone in cervical transforaminal epidural injections. Both groups exhibited statistically and clinically significant improvements in pain at four weeks. The triamcinolone group demonstrated a non–statistically significant trend toward more improvement.

Then, in 2008, O’Donnell22 compared the efficacy of triamcinolone to dexamethasone transforaminal ESI in the treatment of low back and/or radicular pain. Both groups showed statistically significant improvement but more so in the triamcinolone group. This study is limited by its inclusion of patients with both low back pain and lumbar radiculitis. The clinical efficacy of transforaminal injections is documented in patients with radicular pain22 as opposed to low back pain. A recent review concluded that evidence of efficacy was lacking for transforaminal injections
for discogenic low back pain.23 In O’Donnell’s study, a greater prevalence of primary radicular or low back pain in one group or the other could conceivably confound results.

Considerations Concerning What to Inject
Cervical epidurals are arguably the most hazardous of all nonoperative interventional spine procedures. The catastrophic complications associated with cervical transforaminal injections are thought to result from particulate steroids causing embolic infarctions when injected into the vertebral artery or spinal radicular artery.5,6 If appropriate technique is used, the vertebral artery should not be encountered. Even with ideal needle location, the spinal radicular artery can be encountered.5,8,9 Given that the size of particles in commonly used steroids preparations equals or exceeds the caliber of many radicular arteries,13,14 use of a particulate steroid is not wise in cervical transforaminal
injections. In our practice, all interventional physiatrists use dexamethasone.

Cervical interlaminar epidural injections have different considerations. Some have considered this approach to be safer than a transforaminal approach but it still has significant risks which include epidural hematoma, epidural abscess and cord injury from direct needle injury. The concern of arterial embolic infarcts has not been reported with this approach and thus particulate steroids should be safe. Because particulate steroids may be slightly more efficacious,21,22 it is reasonable to use them for interlaminar injections, whether for cervical, thoracic or lumbar injections.

Thoracic and lumbar transforaminal injections also run the risk of arterial vascular injections and embolic infarction leading to neurologic complications. As noted previously, the artery of Adamkiewicz is believed to be a source of major complications.16 Although this artery generally lies above L2, in rare cases it occurs lower. One should be cognizant of this when doing a procedure in this region. Even lumbosacral transforaminal particulate steroid injections have precipitated thoracic paraplegia.

The choice of particulate versus nonparticulate steroids in lumbosacral transforaminal injections is debatable. Even within our practice, there is a variance in what interventionally trained physiatrists use. With appropriate safety measures, particulates may be reasonable.

First, to visualize a vascular injection, inject contrast under live fluoroscopy. In one case of paraplegia after a T12-L1
transforaminal injection, the contrast was injected under lateral fluoroscopic imaging and with the needle at the upper end of the screen.25 Utilizing AP and lateral images as well, positioning the injection in the middle of the screen, may improve the ability to pick up vascular flow with contrast administration. An additional safeguard employs a test dose injection of local anesthetic. In the transient quadriplegia case, a test dose of local anesthetic resulted in symptoms leading to cessation of the procedure. The patient recovered without deficits.10 Fluoroscopic digital subtraction is an invaluable tool in detecting vascular flow. Yet even with ideal needle placement, vascular uptake can be encountered.

Conclusion
In summary, rare but significant complications of transforaminal injections have been associated with injection of particulate steroids. Particulate steroids appear to be slightly more efficacious than nonparticulate steroids but further studies need to be done. In our estimation, it is wise to use a nonparticulate steroid like dexamethasone in cervical and thoracic transforaminal injections. The choice in lumbosacral transforaminal injections is debatable, especially if appropriate safety measures are used. The risk with particulate steroid injections has not been associated with
interlaminar epidural steroid injections nor with intra-articular injections.

References
1. McMillan MR, Crumpton C. Cortical blindness and neurologic injury complicating cervical transforaminal injection for cervical radiculopathy. Anesthesiology. 2003;99:509–511.

2. Rozin L, Rozin R, Koehler SA, et al. Death during a transforaminal epidural steroid nerve root block(C7) due to perforation of the left vertebral artery. Am J Forensic Med Path. 2003;24:351–355.

3. Tiso RL, Cutler T, Catania JA, Whalen K. Adverse central nervous system sequelae after selective transforaminal block: The role of corticosteroids. Spine J. 2004;4:468–474.

4. Brouwers PJAM, Kottnik EJBL, Simon MAM, Prevo RL. A cervical anterior spinal artery syndrome after diagnostic blockade of the right C6-nerve root. Pain. 2001;91:397–399.

5. Baker R, Dreyfuss P, Mercer S, Bogduk N. Cervical transforaminal injection of corticosteroids into a radicular artery: A possible mechanism for spinal cord injury. Pain. 2003;103:211–215.

6. Rathmell JR, Aprill C, Bogduk N. Cervical transforaminal injection of steroids. Anesthesiology. 2004;100:1595–1600.

7. 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;87:1025-1030.

8. Hoeft MA, Rathmell JP, Monsey RD, Fonda BJ. Cervical transforaminal injection and the radicular artery: variation in anatomical location within the cervical intervertebral foramina. Reg Anesth Pain Med. 2006;31:270-274.

9. Huntoon MA, Anatomy of the cervical intervertebral foramina: vulnerable arteries and ischemic neurologic injuries after transforaminal epidural injecitons. Pain. 2005;117:104-111.

10. Karasek M, Bogduk N. Temporary neurologic deficit after cervical transforaminal injection of local anesthetic. Pain Med. 2004;5:202-205.

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

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

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

14. Derby, R, Date E, Lee CH, Lee JH, Lee SH. Size and aggregation of corticosteroids used for epidural injections. Interventional Spine, ISIS Newsletter. 2005 5(4):30-37.

15. 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;90:1932-1938.

16. Bogduk N, Dreyfuss P, Baker R, et al. Complications of spinal diagnostic and treatment procedures. Pain Med. 2008;9:S11-34.

17. Lo D, Vallee JN, Spell L, et al. Unusual origin of the artery of Adamkiewicz from the fourth lumbar artery. Neuroradiology. 2002;44:153-157.

18. Somyaji HS, Saifuddin A, Casey ATH, Briggs TWR. Spinal cord infarction following therapeutic CT-guided left L2 nerve root injection. Spine. 2005;30:E106-108.

19. Houten JK, Errico TJ. Paraplegia after lumbosacral nerve root block: report of three cases. Spine J. 2002;2:70-75.

20. Quintero N, Laffont I, Bouhmidi L, et al. Transforaminal epidural steroid injection and paraplegia: case report and bibliographic review. Ann Readapt Med Phys. 2006;49:242-247.

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

22. O’Donnell C, Cano W, Eramo G. Comparison of triamcinolone to dexamethasone in the treatment of low back pain and leg pain via lumbar transforaminal epidural steroid injection. Spine J. 2008;8:65S.

23. DePalma M, 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;86:1477-1483.

24. DePalma MJ, Slipman CW. Evidence-informed management of chronic low back pain with epidural steroid injections. Spine J. 2008;8:45-55.

25. Glaser SE, Falco F. Paraplegia following a thoracolumbar transforaminal epidural steroid injection. Pain Physician. 2005;8:309-314.

Author Disclosures

• J Beckworth: nothing to disclose
• S Dreyer: Speaking/Teaching Arrangement: Level B, Pfizer.

 See Results.