Early versus Delayed Decompression for Traumatic Cervical Spinal Cord Injury: Results of the Surgical Timing in Acute Spinal Cord Injury Study (STASCIS)

BACKGROUND:There is convincing preclinical evidence that early decompression in the setting of spinal cord injury (SCI) improves neurologic outcomes. However, the effect of early surgical decompression in patients with acute SCI remains uncertain. Our objective was to evaluate the relative effectiveness of early (<24 hours after injury) versus late (≥ 24 hours after injury) decompressive surgery after traumatic cervical SCI. METHODS:We performed a multicenter, international, prospective cohort study (Surgical Timing In Acute Spinal Cord Injury Study: STASCIS) in adults aged 16-80 with cervical SCI. Enrolment occurred between 2002 and 2009 at 6 North American centers. The primary outcome was ordinal change in ASIA Impairment Scale (AIS) grade at 6 months follow-up. Secondary outcomes included assessments of complications rates and mortality. FINDINGS:A total of 313 patients with acute cervical SCI were enrolled. Of these, 182 underwent early surgery, at a mean of 14.2(± 5.4) hours, with the remaining 131 having late surgery, at a mean of 48.3(± 29.3) hours. Of the 222 patients with follow-up available at 6 months post injury, 19.8% of patients undergoing early surgery showed a ≥ 2 grade improvement in AIS compared to 8.8% in the late decompression group (OR = 2.57, 95% CI:1.11,5.97). In the multivariate analysis, adjusted for preoperative neurological status and steroid administration, the odds of at least a 2 grade AIS improvement were 2.8 times higher amongst those who underwent early surgery as compared to those who underwent late surgery (OR = 2.83, 95% CI:1.10,7.28). During the 30 day post injury period, there was 1 mortality in both of the surgical groups. Complications occurred in 24.2% of early surgery patients and 30.5% of late surgery patients (p = 0.21). CONCLUSION:Decompression prior to 24 hours after SCI can be performed safely and is associated with improved neurologic outcome, defined as at least a 2 grade AIS improvement at 6 months follow-up

Guanosine reduces apoptosis and inflammation associated with restoration of function in rats with acute spinal cord injury

Spinal cord injury results in progressive waves of secondary injuries, cascades of noxious pathological mechanisms that substantially exacerbate the primary injury and the resultant permanent functional deficits. Secondary injuries are associated with inflammation, excessive cytokine release, and cell apoptosis. The purine nucleoside guanosine has significant trophic effects and is neuroprotective, antiapoptotic in vitro, and stimulates nerve regeneration. Therefore, we determined whether systemic administration of guanosine could protect rats from some of the secondary effects of spinal cord injury, thereby reducing neurological deficits. Systemic administration of guanosine (8 mg/kg per day, i.p.) for 14 consecutive days, starting 4 h after moderate spinal cord injury in rats, significantly improved not only motor and sensory functions, but also recovery of bladder function. These improvements were associated with reduction in the inflammatory response to injury, reduction of apoptotic cell death, increased sparing of axons, and preservation of myelin. Our data indicate that the therapeutic action of guanosine probably results from reducing inflammation resulting in the protection of axons, oligodendrocytes, and neurons and from inhibiting apoptotic cell death. These data raise the intriguing possibility that guanosine may also be able to reduce secondary pathological events and thus improve functional outcome after traumatic spinal cord injury in humans

Cerebrospinal Fluid Drainage and Induced Hypertension Improve Spinal Cord Perfusion After Acute Spinal Cord Injury in Pigs

BACKGROUND: Acute spinal cord injury (SCI) is commonly treated by elevating the mean arterial pressure (MAP). Other potential interventions include cerebrospinal fluid drainage (CSFD). OBJECTIVE: To determine the efficacy of aggressive MAP elevation combined with intrathecal pressure (ITP) reduction; our primary objective was to improve spinal cord blood flow (SCBF) after SCI. METHODS: All 15 pigs underwent laminectomy. Study groups included control (n = 3); SCI only (n = 3); SCI combined with MAP elevation (SCI + MAP) (n = 3); SCI combined with CSFD (SCI + CSFD) (n = 3); and SCI combined with both MAP elevation and CSFD (SCI + MAP + CSFD) (n = 3). SCBF was measured with laser Doppler flowmetry. RESULTS: In the SCI group, SCBF decreased by 56% after SCI. MAP elevation after SCI resulted in a 34% decrease in SCBF, whereas CSFD resulted in a 59% decrease in SCBF. The combination of CSFD and MAP elevation resulted in a 24% increase in SCBF. The SCI + MAP group had an average ITP increase of 5.45 mm Hg after MAP elevation 1 hour after SCI and remained at that level throughout the experiment. CONCLUSION: Both MAP elevation alone and CSFD alone led to only short-term improvement of SCBF. The combination of MAP elevation and CSFD significantly and sustainably improved SCBF and spinal cord perfusion pressure. Although laser Doppler flowmetry can provide flow measurements to a tissue depth of only 1.5 mm, these results may represent pattern of blood flow changes in the entire spinal cord after injury