India-OrthRole of Steroids in Spinal Cord Injuries
Dr Sanjay Shinde
consultant ortho & spine surgeon, shankar hospital, Akola
orthosanju@gmail.com
Article Is written with help of Collaborative Authorship Programme
Introduction:
Spinal cord injury (SCI) is a devastating event that usually results in significant functional impairment for the patient.
Epidemiology
It is estimated that acute spinal cord injury affects some 40 per million people each year [1], although estimates of incidence may vary considerably between countries. The incidence of SCI is roughly 10,000 to 14,000 new cases per year, with a prevalence of 229,000 to 306,000 patients in the United States alone. [1, 2] Motor vehicle accidents and falls are the most common causes of SCI.
SCIs most commonly occur in young adults in their second or third decade of life.[3] Injuries to the cervical spine make up 55% of all SCIs, with an equal distribution of injuries to the thoracic, lumbar, and lumbosacral areas. Incomplete Quadriparesis is the most frequent neurologic pattern of injury, seen in approximately 30% of SCI patients. [2] Approximately 25% of SCI patients have complete motor and sensory loss caudal to the neurologic level of injury, corresponding to American Spinal Injury Association (ASIA) impairment level A. [2]
Patho-Physiology
SCI is a complex two-step process in which a cascade of secondary neurodegenerative events is set in motion by a primary injury.3 Primary injury mechanisms include acute compression, laceration, shear, distraction, and impaction of the spinal cord. [3] Sustained compression of the spinal cord most often exists in the setting of acutely ruptured disks, fracture-dislocations, burst fractures, and missile injuries, In the animal model, sustained compression of the spinal cord has been shown to lead to a larger histologic lesion, a lack of recovery of somatosensory-evoked potentials, and poorer functional outcomes. [4] The body's response to the initial injury, deemed the secondary injury, leads to a cascade of cellular events perpetuating and extending the SCI. Vascular changes, ionic derangements, accumulation of neurotransmitters, apoptosis, edema, inflammation, loss of ATP-dependent processes, and production of various molecules (ie, arachidonic acid, eicosanoid, endogenous opioids, free radicals) create a toxic milieu, perpetuating the SCI. The secondary injury begins minutes after the initial injury and may last for weeks to months. [4] In an attempt to contain the extent of damage, the injured central nervous system (CNS) forms a glial scar—a potent physical barrier that prevents axonal regrowth through that region. Additionally, proteins, such as chondroitin sulfate glycoproteins, semaphorin 3 proteins, and ephrin tyrosine kinase, are released, concentrating growth factors and deflecting axonal growth away from the zone of injury. Though these proteins assist in axonal recovery, they thwart axonal regrowth through the glial scar. [5] Knowledge of the events of the secondary injury provides a target for therapeutic intervention.
Pharmacologic Treatments
Because the SCI was followed with cascade of inflammatory changes, as a body’s protective & repairing mechanism; this was shown to actually worsen neural damage. Hence researchers started thinking on the ground to curtail this secondary inflammatory damage. Steroids being potent anti-inflammatory drugs available, showing its wonderful effects in other life threatening situations, were obvious choice for this cause.
Methylprednisolone Sodium Succinate
Methylprednisolone sodium succinate (MPSS) is a glucocorticoid with the potential to inhibit inflammatory damage to the spinal cord and exert a cell-stabilizing effect by impeding lipid peroxidation, decreasing the neurotoxicity of excitatory amino acids, increasing blood perfusion in the spinal tissue, and slowing the traumatic shift of ions.
Animal experimentation with pharmacologic therapy for acute spinal cord injury started in the late 1960s, became more common in the 1970s and led, in the USA, to the first National Acute Spinal Cord Injury Study (NASCIS 1) started in1979 and completed in 1984 [10]. As far as can be ascertained, this was the first randomized trial of any therapeutic modality for all aspects of spinal cord injury. The second National Acute Spinal Cord Injury Study followed [11]. Multi center trial from Japan [16] and a single center trial from France [17] both evaluated one of the treatment arms of NASCIS 2 which represents the first replication of a trial in this area. The third NASCIS trial has been reported [12].
Summary of Relevant Studies
Prospective, Randomized Controlled Trials
Study Design Outcome
NASCIS 1 USA, 1984
Prospective, randomized, double-blind. Methylprednisolone, 2 dose regimens.
Negative.
NASCIS 2 USA, 1990
Prospective, randomized, double-blind. Methylprednisolone, Naloxone, Placebo
Significantly improved neurologic recovery with early (<8 h of SCI) MPSS treatment (P = 0.03
Otani Japan, 1994
Prospective, randomized, un-blinded. Methylprednisolone vs Placebo
Improved neurologic and sensory recovery with early treatment (<8 h of SCI)
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