AANS Neurosurgeon | Volume 29, Number 1, 2020


The Evidence is Against the Use of Steroids for Acute Spinal Cord Injury Treatment: Part I

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Spinal cord injuries unfortunately are all too common, even in the developed world where numerous safety advances are aimed at prevention. Patients who survive the initial injury and other serious injuries that accompany spinal cord injury (SCI), will have some degree of permanent paralysis, sensory loss and/or dysautonomia. This ultimately yields a shorter life expectancy for individuals afflicted as well as great economic costs in health care needs and lost productivity. Though improvements in rehabilitative care have abounded, the acute care of spinal cord injury is roughly stagnant with respect to improvement in neurologic outcomes.

Pathophysiology of Spinal Cord Injury

Primary injury caused by the initial impact trauma is the result of shear, laceration, contusion and/or compression. Additionally, acute stretch of neurons, glia or vasculature can also be causative of primary injury. Transection events are rare; blunt mechanisms of injury are far more common. Prevention efforts, and arguably surgery for decompression and stability, are a part of the management of primary injury. 

Critical care management and most bench and bedside research are focused on altering secondary injury. Secondary injury is the delayed progression of injury defined by complex and interrelated molecular processes that progressively damage the spinal cord parenchyma.

Impaired cord perfusion leads to bioenergetic failure at the cellular level. Diminished oxygen delivery to the spinal cord parenchyma results in intracellular acidosis, which disrupts membrane potentials and impairs cell signaling. Moreover, protective intracellular antioxidant enzymes begin to fail in these conditions, just as mitochondrial membrane permeability increases, and radical species are released from within the mitochondria to the intracellular space. The cells will begin to swell as osmotic gradients shift; this is the first of the multiple mechanisms of edema following spinal cord injury.

As the timeline of secondary spinal cord injury progresses, so do additional mechanisms of abnormal cell signaling, ischemia and edema: 

  • Changes in the intracellular conditions of the injured spinal cord parenchyma upregulate neuroinflammatory cascades and increase immune cell recruitment to the area of injury.
  • Immune cells invading the cord can be helpful in clearing myelin debris that will inhibit cell growth during recovery; however, they too can generate harmful free radical species.
  • Free radicals can alter vascular permeability and beget additional edematous changes.
  • Immune cell recruitment can also worsen the microvasculature damaged by the initial traumatic force.
  • With microvasculature injury intravascular stasis, coagulation, thrombosis and distention occur with subsequent leakage of proteinaceous fluid into the surrounding tissues. This in turn increases interstitial pressure and further limits spinal cord perfusion.

Neuroprotection against the secondary injury mechanisms above became the strategic target for pharmacologic intervention. Glucocorticoids were hypothesized to have benefit given their antioxidant properties. Other theoretical effects of glucocorticoids included:

  • Allowing restoration of the blood-CNS barrier to limit vasogenic edema;
  • Blunting of the inflammatory immune response;
  • Stabilization of membrane potentials, inhibition of neurofilament degradation; and
  • Alteration of electrolyte balances in injured tissues.

Of the available glucocorticoid compounds methylprednisolone sodium succinate (MPSS) was chosen for treatment of acute SCI, as it crosses cell membranes more rapidly and completely than other corticoid radicals with less potential neutropenia.

With this understanding and background, Part 2 of this article explores whether the promise of glucocorticoids delivered for patients with SCI.


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