Erythropoietin Plus Methylprednisolone or Methylprednisolone in the Treatment of Acute Spinal Cord Injury: a Preliminary Report
Abstract
Recent studies in animal models indicate that recombinant human erythropoietin (rhEPO) is very effective in enhancing neurological recovery after spinal cord injury (SCI). We aimed to evaluate the effect of rhEPO plus methylprednisolone sodium succinate (MPSS) compared to MPSS alone to improve neurological function of patients after SCI in a randomized clinical trial. During a 15-month period 30 patients presenting to emergency departments of two university affiliated hospitals within less than 6 hours after acute SCI were randomized to two groups. Both groups received MPSS 30 mg/kg initially and 5.4 mg/kg every hour till 23 hours if admitted within 3 hours and till 47 hours if recruited within 3-6 hours after injury. Group EPO also received 500 unit/kg rhEPO on admission and another 500 unit/kg 24 hours later instead of placebo in group MPSS. Neurologic evaluation was performed on admission, 24, 48, 72 hours and one and 6 months later. Range of patients' age was 18-65 years. There was no significant difference between patients receiving two types of treatment in neurological exam on admission (P=0.125), 24 hours after admission (P=0.108) and 48 hours after admission (P=0.085). However, one week (P=0.046), one month (P=0.021) and six months (P=0.018) after admission these differences were significant. MPSS plus rhEPO started within 6 hours after acute spinal injury may be more effective than MPSS plus placebo in improvement of neurologic dysfunction. More studies with larger sample sizes are warranted.
Sekhon LH, Fehlings MG. Epidemiology, demographics and pathophysiology of acute spinal cord injury. Spine 2001;26(24 Suppl):S2-12.
Hawryluk GW, Rowland J, Kwon BK, et al. Protection and repair of the injured spinal cord: a review of completed, ongoing and planned clinical trials for acute spinal cord injury. Neurosurg Focus 2008;25(5):E14.
Hugenholtz H. Methylprednisolone for acute spinal cord injury: not a standard of care. CMAJ 2003;168(9):1145-6.
Bernaudin M, Marti HH, Roussal S, et al. A potential role for erythropoietin in focal permanent cerebral ischemia in mice. J Cereb Blood Flow Metab 1999;19(6):643-51.
Hasselblatt M, Ehrenreich H, Siren AL. The brain erythropoietin system and its potential for therapeutic exploitation in brain disease. J Neurosurg Anesthesiol 2006;18(2):132-8.
American Spinal Injury Association: International standards for neurological classifications of spinal cord injury. Scireport. (Accessed in Feb 5, 2014, at www.scireproject.com/.../american-spinal-injuryassociation-international...).
Ditunno JF Jr, Young W, Donovan WH, et al. The international standards booklet for neurological and functional classification of spinal cord injury. Paraplegia 1994;32(2):70-80.
Cetin A, Nas K, Buyukbayram H, et al. The effects of systemically administrated methylprednisolone and recombinant human erythropoietin after acute spinal cord injury in rats. Eur spine J 2006;15(10):1539-44.
Fehlings MG, Baptiste DC. Current status of clinical trials for acute spinal cord injury. Injury 2005;36(Suppl2):B113-22.
Kasper C. Erythropoietin. In: Thomson AW, Lotze MT, editors. The cytokine handbook. 4th ed. London: Elsevier; 2003: p. 149-66.
Jia H, Feng X, Li W, et al. Recombinant human erythropoietin attenuates spinal neuroimmune activation ofneuropathic pain in rats. Ann Clin Lab Sci 2009;39(1):84-91.
Ning B, Zhang A, Song H, et al. Recombinant human erythropoietin prevents motor neuron apoptosis in a ratmodel of cervical sub-acute spinal cord compression. Neurosci Lett 2011;490(1):57-62.
Mofidi A, Bader A, Pavlica S. The use of erythropoietin and its derivatives to treat spinal cord injury. Mini Rev Med Chem 2011;11(9):763-70.
Cerri G, Montagna M, Madaschi L, et al. Erythropoietin effect on sensorimotor recovery after contusive spinal cord injury: an electrophysiological study in rats. Neuroscience 2012;219(1):290-301.
Ehrenreich H, Hasselblatt M, Dembowski C, et al. Erythropoietin therapy for acute stroke is both safe and beneficial. Mol Med 2002;8(8):495-505.
King VR, Averill SA, Hewazy D, et al. Erythropoietin and carbamylated erythropoietin are neuroprotective following spinal cord hemi section in rat. Eur J Neurosci 2007;26(1):90-100.
Okutan O, Solaroglu I, Beskonakli E,et al. Recombinant human erythropoietin decreases myeloperoxidase and caspase-3 activity and improves early functional results after spinal cord injury in rats. J Clin Neurosci 2007;14(4):364-8.
Steeves JD, Lammertse D, Curt A, et al. Guidelines for the conduct of clinical trials for spinal cord injury as developed by ICCP panel: Clinical trial outcome measures. Spinal Cord 2007;45(3):206-21.
Angello D, Bigini P, Villa P, et al. Erythropoietin exerts an anti-inflammatory effect on the CNS in a model of experimental autoimmune encephalomyelitis. Brain Res 2002;952(1):128-34.
Brines M, Cerami A. Erythropoietin in spinal cord injury. In: Hoke A, editor. Erythropoietin and the nervous system. Novel therapeutic options for neuroprotection. New York: Springer; 2006: 147-64.
Files | ||
Issue | Vol 52, No 4 (2014) | |
Section | Original Article(s) | |
Keywords | ||
Pinal cord Erythropoietin Methylprednisolone sodium succinate Trauma |
Rights and permissions | |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |