Pathogenic Mechanisms of a Stroke-like attack Elicited by Epidural Steroid Injection Therapy

Author(s): Zhen He*

Journal Name: Current Neurovascular Research

Volume 17 , Issue 3 , 2020

Become EABM
Become Reviewer
Call for Editor


Background: The pathogenic mechanisms involved in a disastrous scenario, following epidural steroid injections (ESI), remain unclarified. Intra-arterial injection of steroids with needlepenetrating vascular injury would be the culprit, as particulate medicine elicits a brain or spinal cord stroke-like attack.

Methods: On the other hand, the limited experimental approaches simulating an accidental steroid intra-arterial injection for ESI conflicted in their results: hemorrhage vs. ischemia.

Results: This article dissects the potential pathogenic mechanisms at a neurovascular unit. Noticeably, a schematic representation provides an explanation of how emboli formed by particulate steroids elicit either hemorrhagic, or ischemic lesion.

Conclusion: In addition, the development of a rat model with intravertebral artery steroid injection is a proposal to address the unmet need in evaluating steroids and vascular injury in ESI.

Keywords: Epidural steroid injections, stroke, living neurovascular unit, pathogenic mechanism, particulate steroids, spinal cord.

FDA briefing document: epidural steroid injections (ESI) and the risk of serious neurologic adverse reactions. Anesthetic and analgesic drug products advisory committee meeting November 24-25, 2014.. 20Documents/The%20Pink%20Sheet%20DAILY/2014/November/ 112114%20FDA%20edpidural%20adcom%20background.pdf
Manchikanti L, Hirsch JA. Neurological complications associated with epidural steroid injections. Curr Pain Headache Rep 2015; 19(5): 482.
[] [PMID: 25795154]
He Z, Cui L, Ferguson SA, Paule MG. Epidural steroid injection therapy, complications and experimental approaches simulating accidental intra-arterial injection. J Neurol Disord Stroke 2016; 4(2): 1113.
Huntoon MA. Anatomy of the cervical intervertebral foramina: vulnerable arteries and ischemic neurologic injuries after transforaminal epidural injections. Pain 2005; 117(1-2): 104-11.
[] [PMID: 16055268]
Rathmell JP, Aprill C, Bogduk N. Cervical transforaminal injection of steroids. Anesthesiology 2004; 100(6): 1595-600.
[] [PMID: 15166582]
Rathmell JP, Benzon HT, Dreyfuss P, et al. Safeguards to prevent neurologic complications after epidural steroid injections: consensus opinions from a multidisciplinary working group and national organizations. Anesthesiology 2015; 122(5): 974-84.
[] [PMID: 25668411]
Benzon HT, Huntoon MA, Rathmell JP. Improving the safety of epidural steroid injections. JAMA 2015; 313(17): 1713-4.
[] [PMID: 25822848]
Diehn FE, Murthy NS, Maus TP. Science to practice: what causes arterial infarction in transforaminal epidural steroid injections, and which steroid is safest? Radiology 2016; 279(3): 657-9.
[] [PMID: 27183400]
Dawley JD, Moeller-Bertram T, Wallace MS, Patel PM. Intra-arterial injection in the rat brain: evaluation of steroids used for transforaminal epidurals. Spine 2009; 34(16): 1638-43.
[] [PMID: 19770605]
Manchikanti L, Candido KD, Singh V, et al. Epidural steroid warning controversy still dogging FDA. Pain Physician 2014; 17(4): E451-74.
[PMID: 25054397]
Popescu A, Lai D, Lu A, Gardner K. Stroke following epidural injections--case report and review of literature. J Neuroimaging 2013; 23(1): 118-21.
[] [PMID: 21699610]
Ibrahim AS, Tawfik AM, Hussein KA, et al. Pigment epithelium-derived factor inhibits retinal microvascular dysfunction induced by 12/15-lipoxygenase-derived eicosanoids. Biochim Biophys Acta 2015; 1851(3): 290-8.
[] [PMID: 25562624]
He Z, He YJ, Day AL, Simpkins JW. Proestrus levels of estradiol during transient global cerebral ischemia improves the histological outcome of the hippocampal CA1 region: perfusion-dependent and-independent mechanisms. J Neurol Sci 2002; 193(2): 79-87.
[] [PMID: 11790387]
Benzon HT, Chew TL, McCarthy RJ, Benzon HA, Walega DR. Comparison of the particle sizes of different steroids and the effect of dilution: a review of the relative neurotoxicities of the steroids. Anesthesiology 2007; 106(2): 331-8.
[] [PMID: 17264728]
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): 468-74.
[] [PMID: 15246308]
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): 1932-8.
[] [PMID: 18762654]
Kim JS, Han YS. Medial medullary infarction: clinical, imaging, and outcome study in 86 consecutive patients. Stroke 2009; 40(10): 3221-5.
[] [PMID: 19628797]
Cole DJ, Matsumura JS, Drummond JC, Schultz RL, Wong MH. Time- and pressure-dependent changes in blood-brain barrier permeability after temporary middle cerebral artery occlusion in rats. Acta Neuropathol 1991; 82(4): 266-73.
[] [PMID: 1759559]
He Z, Cui L, Ferguson SA, Paule MG. A Working Module for the Neurovascular Unit in the Sexually Dimorphic Nucleus of the Preoptic Area. Mol Neurobiol 2018; 55(1): 156-63.
[] [PMID: 28840477]
He Z, Patterson TA. A Potential Role for the Existence of Pericytes in the Neurovascular Unit of the Sexually Dimorphic Nucleus of the Rat Preoptic Area to Control Blood-Brain Barrier Function. Curr Neurovasc Res 2019; 16(3): 194-201.
[] [PMID: 31244439]
Hatan M, Shinder V, Israeli D, et al. Pigment epithelium-derived factor inhibits retinal microvascular dysfunction induced by 12/15-lipoxygenase-derived eicosanoids. Biochim Biophys Acta 2011; 1851(3): 290-8.
Kaneko D, Nakamura N, Ogawa T. Cerebral infarction in rats using homologous blood emboli: development of a new experimental model. Stroke 1985; 16(1): 76-84.
[] [PMID: 3966271]
He Z, Meschia JF, Brott TG, Dickson DW, McKinney M. Aging is neuroprotective during global ischemia but leads to increased caspase-3 and apoptotic activity in hippocampal neurons. Curr Neurovasc Res 2006; 3(3): 181-6.
[] [PMID: 16918382]
He Z, He B, Behrle BL, et al. Ischemia-induced increase in microvascular phosphodiesterase 4D expression in rat hippocampus associated with blood brain barrier permeability: effect of age. ACS Chem Neurosci 2012; 3(6): 428-32.
[] [PMID: 22860212]
Lee RM. Morphology of cerebral arteries. Pharmacol Ther 1995; 66(1): 149-73.
[] [PMID: 7630927]

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2020
Published on: 15 April, 2020
Page: [312 - 318]
Pages: 7
DOI: 10.2174/1567202617666200415143201
Price: $65

Article Metrics

PDF: 25