Scientific Journal

Scientific Journal of the Hellenic Companion Animal Veterinary Society (HCAVS)


Hellenic Journal of Companion Animal Medicine - Volume 8 - Issue 2 - 2019

Corticosteroids in acute traumatic injury of the central nervous system

George Kazakos DVM, PhD, Eirini Sarpekidou DVM

Companion Animal Clinic, School of Veterinary Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece


Acute traumatic injury of the central nervous system, both of the spinal cord and the brain, can lead to permanent damage in both organs. Despite the theoretical benefits and the inclusion of corticosteroids in the management of such cases for many years, substantiated and clinical value from these drugs has not been identified thus far, therefore their usefulness has been questioned (Alderson & Roberts 1997).

Spinal cord

Injury to the spinal cord can result in trauma because of concussion, compression, rupture or hyperextension of the spinal cord or its vascular bed. Within minutes of the original primary damage, a cascade of events which causes secondary injury is initiated, only to be completed in a few days (Tator & Fehlings 1991, Olby 1999, Dumont et al. 2001, Hall & Springer 2004, Olby 2010, Park et al. 2012). The latter is characterised by ischemia, cellular oedema, disruption in the levels of neurotransmitters, and increase in inflammatory mediators such as prostanoids, nitric oxide etc., finally leading to neuronal necrosis and apoptosis. Ischaemia, inflammation and haemorrhage can lead to the formation of free oxygen radicals, which result in lipid peroxidation of fatty acids across cellular membranes, therefore contributing to neuronal death (Tator & Fehlings 1991, Olby 1999, Dumont et al. 2001, Hall & Springer 2004, Olby 2010, Park et al. 2012).

Experimental data
Corticosteroids are considered to protect the spinal cord in cases of traumatic injury, through their effect on developing inflammation and ischaemia during secondary injury, as well as through another, unrelated pathway (Braughler & Hall 1983a, Hall et al. 1984, Hall 1992, Hall & Springer 2004).

  Experimental studies in cats have indicated that the administration of very high -much higher than anti-inflammatory- doses of methylprednisolone sodium succinate (MSS) for 48 hours have limited ischaemia, lipid peroxidation of fatty acids, intracellular accumulation of calcium, the formation of prostanoids and the deconstruction of neurons (Braughler & Hall 1983a, Hall et al. 1984, Hall 1992, Hall & Springer 2004). Moreover, injury site perfusion was improved, formation of free oxygen radicals was limited and finally, the changes in neurological status following injury were more positive and histopathology revealed reduced loss of neuronal tissue (Braughler & Hall 1983 , Hall et al. 1984, Braughler et al. 1987, Hall 1992, Hall & Springer 2004).

  Another corticosteroid agent, dexamethasone, with an anti-inflammatory effect several times more powerful to that of methylprednisolone, and a greater affinity for corticosteroid receptors, has not been proven to be advantageous when administered after spinal cord trauma in rats, considering that methylprednisolone had a more active role as an antioxidant (Hoerlein et al. 1983, Bracken et al. 1984, Faden et al. 1984, Braughler 1985, Braughler & Hall 1985, Arias 1987, Hall & Springer 2004, Schimmer & Parker 2006).

  There are not enough experimental data in dogs. In a study on spinal cord trauma, the administration of methylprednisolone did not improve the final outcome (Coates et al. 1995). In another experimental study, where spinal cord trauma was inflicted in dogs, the use of very high doses of methylprednisolone along with surgical decompression of the spinal cord led to slight improvement of neurological outcome, compared to surgical decompression alone, however this difference was statistically non-significant (Rabinowitz et al. 2008). Moreover, in other studies increased neuronal apoptosis was observed after the administration of steroids following central nervous system trauma, perhaps because of the increased oxidative stress resulting from suppression of phospholipase A2 activity of the cellular membrane and accumulation of lactic acid in the spinal cord (Braughler & Hall ED 1983a, Braughler & Hall 1983b, Braughler & Hall 1984, Sapolsky 1994, Hall & Springer 2004).

Clinical data
Corticosteroid use in acute spinal cord traumatic injury in routine practice is questioned both in humans and animals. Despite occasional reports mentioning a reduction in morbidity and mortality, and improvement on functional restoration of the spinal cord and quality of life, these reports are not widely accepted, and also corticosteroid side effects have been reported.

  The three national American studies on spinal cord traumatic injury (National American Spinal Cord Injury Study, NASCIS I, II, III) (Bracken et al. 1985, Bracken et al. 1990, Bracken et al. 1997) indicated small but substantial improvements of sensation and mobility in humans with acute spinal cord trauma to which very high doses of MSS had been administered within 3-8 hours post-trauma. Based on these studies, patients to which very high doses of MSS had been administered within less than 3 hours post-trauma, continued to receive it for 24 hours, whereas those to whom the first dose was given between 3 and 8 hours continued to receive it for 48 hours. It is worth mentioning that it was not recommended to initiate treatment after 8 hours post-trauma (Bracken et al. 1985, Fehlings 2001, Hall & Springer 2004). Despite the small statistically significant improvement in the results of sensation and mobility functional testing, when functional autonomy was evaluated there was no statistically significant difference compared to patients who had not received MSS (Bracken et al. 1997). A retrospective review in the Cohrane, PubMed, and EMBASE databases seemed to agree with this treatment plan, even though it did report that return to normal function was not expected for any impairments (Bracken 2012). A while later, in the management guidelines published in 2013 by the American Board of Spine Surgery it was reported that MSS has no place in the treatment of acute spinal cord traumatic injury. There was a difference of opinion regarding the use of MSS. Study results for MSS administration to patients have three main flaws. Firstly, they stem from retrospective evaluation of subgroups of patients from the original studies, secondly their data are incomplete and thirdly the neurological outcome is unclear, meaning that this drug is shown to be effective for prevention in patients with improved sensation but not mobility or with improved mobility but not sensation, and furthermore under no circumstances was the neurological improvement functionally significant (Hurlbert 2013). Therefore, despite the existence of other prospective clinical studies regarding the use of MSS in management of spinal cord traumatic injury, it is recognized that no advantage has been substantiated from MSS administration on the long term outcome of such cases, whereas there is increased risk of complications, mostly from the digestive tract (Evaniew et al. 2016). Despite all of the above, the Board of Spine Surgery recognizing the lack of evidence, still supports the administration of MSS if this is initiated up to 8 hours post-trauma, however without including it in the guidelines (Fehlings 2017). On the contrary, in the most recent (2017) 10th edition of the Student Book of Advanced Trauma Life Support (ATLS) of the American College of Surgeons it is explicitly stated that corticosteroids have no place in the management of acute spinal cord injury (ATLS, Student Book 2017 p. 144).

  Companion animals
  Already published studies in dogs and cats regarding acute spinal cord traumatic injury are few in number and mostly report intervertebral disk (IVD) herniation and possible benefits and/or complications from corticosteroid use along with other treatment plans for this specific condition, such as surgical decompression. In general, improvement of neurological status is questionable and furthermore complications from corticosteroid use have been reported, such as large intestinal perforation and ulceration of the gastric mucosa (Henderson & Webster 2006). Moreover, in two retrospective studies there was no improvement either in return to normal function or in the speed of recovery in cases that received any corticosteroid agent perioperatively, compared to cases that had no corticosteroids administered (Davis & Brown 2002, Ruddle et al. 2006).

  In another retrospective study in dogs with spinal cord traumatic injury with surgical management of the inciting cause, the administration of prednisolone sodium succinate had a high complication rate, such as diarrhoea, haematochezia, melaena, vomiting and haematemesis, in various combinations. The authors have reported, however, that management was successful and without prolonged hospitalisation (Culbert et al. 1998).

  When parenteral administration of dexamethasone was combined with orally administered prednisolone in surgically managed cases of IVD herniation, erosions of the gastric mucosa were observed by endoscopy in 76% of these cases (Neiger et al. 2000).

  Dachshund dogs underwent spinal cord decompression surgery for IVD herniation to which MSS was administered had a higher complication rate, higher hospitalisation costs, prolonged hospitalisation times, as well as increased need of gastroprotective agents, compared to dogs receiving a combination of dexamethasone and prednisolone (Boag et al. 2001).

  On the other hand, regarding dexamethasone, in a different retrospective study in dogs it was found that administering it prior to surgical decompression of IVD herniation, this agent caused up to 3.4 times higher complication rates than that in dogs in which a different corticosteroid or no corticosteroids were administered (Levine et al. 2008). In particular, these side effects were located in the gastrointestinal and urinary tract. It should be noted that no difference was observed in neurological status between the groups at the end of hospitalisation as well as during re-examination (Levine et al. 2008). It is worthy of note that there is a retrospective study in dogs, in which the administration of corticosteroids as treatment for IVD herniation was successful (improvement in neurological status, without recurrence of clinical signs) when the herniation was located in the cervical spine, whereas when it was located in the thoracolumbar spine there was no improvement in the quality of life or the final outcome (Levine et al. 2007, Levine et al. 2008).

  Therefore, most of the data regarding the role of corticosteroids in acute spinal cord trauma come from their use in managing cases of IVD herniation, therefore there is no strong evidence that corticosteroid administration is beneficial in the neurological recovery of such cases (Boag et al. 2001, Davis & Brown 2002, Ruddle et al. 2006, Levine et al. 2007).

  Furthermore, corticosteroid administration has been associated with complications from the digestive and urinary tract. Dexamethasone has been implicated to have the most complications in the already published literature (Neiger et al. 2000, Boag et al. 2001, Henderson & Webster 2006, Levine et al. 2007, Levine et al. 2008).

  Therefore, because of the lack of sufficient experimental and clinical evidence in companion animals, as well as of the weak evidence and conflicting opinions in human medicine, the use of corticosteroids cannot be recommended in the management of acute spinal cord traumatic injury in companion animals.


Traumatic brain injury results in primary as well as secondary damage to the brain similar to that after acute spinal cord trauma. One of the most severe consequences is cerebral oedema and increase in intracranial pressure. Considering that corticosteroids have an effect against vasogenic oedema in tumours (Dietrich et al. 2011), they are anti-inflammatories and NASCI’s research studies indicated benefit from their timely use in acute traumatic spinal cord injury, the administration of corticosteroids has been evaluated in traumatic brain injury. Despite their theoretically beneficial effect, this has not been proven in the clinical setting (Alderson & Roberts 1997). This may be due to the different nature of oedema resulting from trauma, which is cytotoxic instead of vasogenic, as in most tumours (Unterberg et al. 2004, Werner & Engelhard 2007, Greve & Zink 2009, Donkin & Vink 2010).

  Moreover, in humans it has been reported that corticosteroid administration within the first 24 hours post-trauma increases the risk for post-traumatic epilepsy (Watson et al. 2004). The administration of corticosteroids causes hyperglycaemia and insulin resistance. Hyperglycaemia after traumatic brain injury has been associated with a poor outcome in humans and increased severity even if it is iatrogenic in companion animals (Syring et al. 2001, Rostam 2014). It is theorised that it amplifies secondary damage through the production of neural stimulators, lactic acid, changes in pH and osmolality (Rostam 2014). The treatment guidelines for traumatic brain injury since 2007 have stated that corticosteroids do not reduce intracranial pressure or improve the neurological outcome and additionally may have harmful consequences (Bratton et al. 2007).

  Moreover, cortisone has been found to be associated with the highest number of deaths in the group of patients with traumatic brain injury which received it as part of the CRASH study (Corticosteroid Randomisation After Significant Head Injury) (Roberts et al. 2004). Therefore, it is no longer recommended as part of the treatment of traumatic brain injury in humans (Alderson & Roberts 2005, Bratton et al. 2007). However, despite avoidance of cortisone in patients with traumatic brain injury, low doses of cortisone are indicated in cases of adrenal insufficiency syndrome in severely affected patients (Asehnoune et al. 2014). The same applies in cases in which there has been damage to the hypothalamus and pituitary gland as a result of traumatic injury, consequently resulting in reduced levels of hormones such as thyroid-stimulating hormone, adrenocorticotropic hormone, vasopressin and growth hormone (Cohan et al. 2005, Hannon et al. 2013). This condition has been described in dogs and was characterised by hypotension and hypoglycaemia. It was managed with small doses of corticosteroids (Foley et al. 2009).

  However, the use of corticosteroids in central nervous system traumatic injury has not been clinically or experimentally studied in companion animals. Therefore, by taking into consideration the studies in humans and despite any limitations, it is not recommended to administer corticosteroids in cases of cranial trauma.

  In conclusion, the effect of corticosteroids on various body systems is known and substantial. However, in cases of central nervous system trauma, data from research in humans as well as companion animals for the administration of corticosteroids are either absent or conflicting. Moreover, corticosteroids cause an increase of morbidity in the already studied populations. Therefore, even though there is no sufficient evidence for guidelines to be formed, the use of corticosteroids cannot be recommended.



  • Alderson P, Roberts I (1997) Corticosteroids in acute traumatic brain injury: systematic review of randomised controlled trials. Br Med J 314, 1855–1859.
  • Alderson P, Roberts I (2005) Corticosteroids for acute traumatic brain injury (Review). Cochrane Database Syst Rev 25, CD000196.
  • Arias MJ (1987) Treatment of experimental spinal cord injury with TRH, naloxone, and dexamethasone. Surg Neurol 28, 335–338.
  • Asehnoune K, Seguin P, Allary J, et al. (2014) Hydrocortisone and fludrocortisone for prevention of hospital-acquired pneumonia in patients with severe traumatic brain injury (Corti-TC): a doubleblind, multicentrephase3, randomised placebo-controlled trial. Lancet Respir Med 2, 706–716.
  • Boag AK, Otto CM, Drobatz KJ (2001) Complications of methylprednisolone sodium succinate therapy in dachshunds with surgically treated intervertebral disc disease. J Vet Emerg Crit Care 11, 105–110.
  • Bracken MB, Collins WF, Freeman DF, et al. (1984) Efficacy of methylprednisolone in acute spinal cord injury. J Am Med Assoc 251, 45–52.
  • Bracken MB, Shepard MJ, Collins WF, et al. (1990) A randomized controlled trial of methylprednisolone or naloxone in the treatment of acute spinal cord injury—results of the Second National Acute Spinal Cord Injury Study. N Engl J Med 322, 1405–1411.
  • Bracken MB, Shepard MJ, Hellenbrand KG, et al. (1985) Methylprednisolone and neurological function 1 year after spinal cord injury— results of the National Acute Spinal Cord Injury Study. J Neurosurg 63, 704–713.
  • Bracken MB, Shepard MJ, Holford R, et al. (1997) Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury—results of the Third National Acute Spinal Cord Injury randomized controlled trial. J Am Med Assoc 277, 1597–1604.
  • Bracken MB (2012). Steroids for acute spinal cord injury (Review). Cochrane Database Syst Rev 18, CD001046.
  • Bratton S, Bullock MR, Carney N (2007) Guidelines for the management of severe traumatic brain injury. J Neurotrauma 24, S1–S106.
  • Braughler JM, Hall ED, Means ED, et al. (1987) Evaluation of an intensive methylprednisolone sodium succinate dosing regimen in experimental spinal cord injury. J Neurosurg 67,102–105.
  • Braughler JM, Hall ED (1984) Effects of multi-Dose methylprednisolone sodium succinate administration on injured cats spinal cord neurofilament degradation and energy metabolism. J Neurosurg 61, 290–295.
  • Braughler JM, Hall ED (1985) Current application of “high-dose” steroid therapy for CNS injury. J Neurosurg 62, 806–810.
  • Braughler JM, Hall ED (1983a) Uptake and elimination of methylprednisolone from contused cat spinal cord following intravenous injection of the sodium succinate ester. J Neurosurg 58, 53–42.
  • Braughler JM, Hall ED (1983b) Lactate and pyruvate metabolism in injured cat spinal cord before and after a single large intravenous dose of methylprednisolone lactate. J Neurosurg 59, 256–261.
  • Braughler JM (1985) Lipid peroxidation-induced inhibition of gamma aminobutyric acid uptake in rat brain synaptosomes: protection by glucocorticoids. J Neurochem 44, 1282–1288.
  • Coates JR, Sorjonen DC, Simpson ST, et al. (1995) Clinicopathologic effects of a 21-aminosteroid compound (U74389G) and high-Dose methylprednisolone on spinal cord function after simulated spinal cord trauma. Vet Surg 24, 128–139.
  • Cohan P, Wang C, McArthur DL, et al. (2005) Acute secondary adrenal insufficiency after traumatic brain injury: a prospective study. Crit Care Med 33, 2358–2366.
  • Culbert LA, Marino DJ, Baule RM, et al. (1998) Complications associated with high-dose prednisolone sodium succinate therapy in dogs with neurological injury. J Am Anim Hosp Assoc 34, 129–134.
  • Davis GJ, Brown DC (2002) Prognostic indicators for time to ambulation after surgical decompression in non-ambulatory dogs with acute thoracolumbar disk extrusions: 112 cases. Vet Surg 31, 513–518.
  • Dietrich J, Rao K, Pastorino S, et al. (2011) Corticosteroids in brain cancer patients: benefits and pitfalls. Expert Rev Clin Pharmacol 4, 233–242.
  • Donkin JJ, Vink R (2010) Mechanisms of cerebral edema in traumatic brain injury: therapeutic developments. Curr Opin Neurol 23, 293–299.
  • Dumont RJ, Okonkwo DO, Verma S (2001) Acute spinal cord injury, part I: pathophysiologic mechanisms. Clin Neuropharmacol 24, 254–264.
  • Faden AI, Jacobs TP, Patrick DH, et al. (1984) Megadose corticosteroid therapy following experimental traumatic spinal injury. J Neurosurg 60, 712–717.
  • Fehlings MG (2001) Recommendations regarding the use of methylprednisolone in acute spinal cord injury: making sense out of the controversy. Spine 26, S56–S57.
  • Foley C, Bracker K, Drellich S (2009) Hypothalamic-pituitary axis deficiency following traumatic brain injury in a dog. J Vet Emerg Crit Care 19, 269–274.
  • Greve MW, Zink BJ (2009) Pathophysiology of traumatic brain injury. Mt Sinai J Med 76, 97–104.
  • Hall ED, Springer JE (2004) Neuroprotection and acute spinal cord injury: a reappraisal. NeuroRx 1, 80–100.
  • Hall ED, Wolf DL, Broughler JM (1984) Effects of a single large dose of methylprednisolone sodium succinate on experimental posttraumatic spinal cord ischemia. J Neurosurg 61, 124–130.
  • Hall ED (1992) The neuroprotective pharmacology of methylprednisolone. J Neurosurg 76, 13–22.
  • Hannon MJ, Crowley RK, Behan LA, et al. (2013) Acute glucocorticoid deficiency and diabetes insipidus are common after acute traumatic brain injury and predict mortality. J Clin Endocrinol Metab 98, 3229–3237.
  • Henderson AK, Webster CRL (2006) Disruption of the gastric mucosal barrier in dogs. Compend Contin Educ Pract Vet 28, 340–357.
  • Hoerlein BF, Redding RW, Hoff EJ, et al. (1983) Evaluation of dexamethasone, DMSO, mannitol, and solcoseryl in acute spinal cord trauma. J Am Anim Hosp Assoc 19, 216–226.
  • Hurlbert RJ, Hadley MN, Walters BC et al. (2013) Pharmacological therapy for acute spinal cord injury. Neurosurgery 72, 93–105.
  • Levine JM, Levine GJ, Johnson SI, et al. (2007) Evaluation of the success of medical management for presumptive cervical intervertebral disk herniation in dogs. Vet Surg 36, 492–499.
  • Levine JM, LevineGJ, BoozerL, et al. (2008) Adverse effects and outcome associated with dexamethasone administration in dogs with acute thoracolumbar intervertebral disk herniation: 161 cases (2000–2006). J Am Vet Med Assoc 232, 411–417.
  • Neiger R, Gaschen F, Jaggy A (2000) Gastric mucosal lesions in dogs with acute intervertebral disc disease: characterization and effects of omeprazole or misoprostol. J Vet Intern Med 14, 33–36.
  • Neiger R, Gaschen F, Jaggy A (2000) Gastric mucosal lesions in dogs with acute intervertebral disc disease: characterization and effects of omeprazole or misoprostol. J Vet Intern Med 14, 33–36.
  • Olby N (1999) Current concepts in the management of acute spinal cord injury. J Vet Intern Med 13, 399–407.
  • Olby N (2010) The pathogenesis and treatment of acute spinal cord injuries in dogs. Vet Clin North Am Small Anim Pract 40, 791–807.
  • Park EH, White GA, Tieber LM (2012) Mechanisms of injury and emergency care of acute spinal cord injury in dogs and cats. J Vet Emerg Crit Care 22, 160–178.
  • Rabinowitz RS, Eck JC, Harper CM, et al. (2008) Urgent surgical decompression compared to methylprednisolone for the treatment of acute spinal cord injury. Spine 33, 2260–2268.
  • Roberts I, Yates D, Sandercock P, et al. (2004) Effect of intravenous corticosteroids on death within 14 days in 10008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial. Lancet 364, 1321–1328.
  • Rostami E (2014) Glucose and the injured brain-monitored in the neurointensive care unit. Front Neurol 5, 91.
  • Ruddle TL, Allen DA, Schertel ER, et al. (2006) Outcome and prognostic factors in non-ambulatory Hansen type I intervertebral disc. Vet Comp Orthop Traumatol 19, 29–34.
  • Sapolsky RM (1994) Glucocorticoids, stress and exacerbation of excitotoxic neuron death. Semin Neurosci 6, 323–331.
  • Schimmer BP, Parker KL (2006) Adrenocorticotropic hormone; adrenocortical steroids and their synthetic analogs; inhibitors of the synthesis and actions of adrenocortical hormones. In: Brunton LL, Lazo JS, Parker KL. eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 11th edn. McGraw-Hill, New York, pp. 1587–1612.
  • Syring RS, Otto CM, Drobatz KJ (2001) Hyperglycemia in dogs and cats with head trauma: 122 cases (1997-1999). J Am Vet Med Assoc 218, 1124-1129.
  • Tator CH, Fehlings MG (1991) Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms. J Neurosurg 75, 15–26.
  • Unterberg AW, Stover J, Kress B, et al. (2004) Edema and brain trauma. Neuroscience 129, 1021–1029.
  • Watson NF, Barber JK, Doherty MJ, et al. (2004) Does glucocorticoid administration prevent late seizures after head injury. Epilepsia 45, 690–694.
  • Werner C, Engelhard K (2007) Pathophysiology of traumatic brain injury. Br J Anaesth 99, 4–9.



Quick Links

Social Media

Contact us

Hellenic Journal of
Companion Animal Medicine

Apollo Tower
64 Louizis Riankour Street,
115 23 Athens
Tel.: +30 210 7759727
Fax.: +30 210 7753460