Diagnosis and Acute Management of Spinal Cord Injury: Current Best Practices and Emerging Therapies

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American Association of Neurological Surgeons (AANS) and the Congress of Neurological Surgeons (CNS), Section on Disorders of the Spine and Peripheral Nerves. Guidelines for the management of acute cervical spine and spinal cord injuries. 2013. Provides numerous updates to the previous 2002 publication of evidence-based management guidelines. Unfortunately, no recommendations are made regarding timing of surgery, and the guideline for methylprednisolone is changed to “treatment not recommended” in contrast to a Cochrane review that recently demonstrated modest efficacy.

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Fehlings MG, Vaccaro A, Wilson JR, et al. Early versus delayed decompression for traumatic cervical spinal cord injury: results of the Surgical Timing in Acute Spinal Cord Injury Study (STASCIS). PLoS One. 2012;7, e32037. Provides numerous updates to the previous 2002 publication of evidence-based A prospective non-randomized study of 313 cervical SCI patients showing that decompressive surgery within the first 24 hours (mean 14.2 h) confers a 2.83 times (95% CI 1.10–7.28) higher chance of a 2-grade AIS improvement compared with after 24 h (mean 48.3 h), with no difference in complication rates (early 24% vs. late 30%, p  = 0.21).

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Aarabi B, Walters BC, Dhall SS, et al. Subaxial cervical spine injury classification systems. Neurosurgery. 2013;72:170–86.

Stroman PW, Wheeler-Kingshott C, Bacon M, et al. The current state-of-the-art of spinal cord imaging: methods. NeuroImage. 2014;84:1070–81. Provides a technical description of five emerging methods of imaging that have the potential to dramatically alter the field by non-invasively characterizing microstructure and functional connectivity of the spinal cord, including diffusion tensor imaging, magnetization transfer, myelin water fraction, magnetic resonance spectroscopy, and functional MRI.

Cohen-Adad J, El Mendili MM, Lehéricy S, et al. Demyelination and degeneration in the injured human spinal cord detected with diffusion and magnetization transfer MRI. NeuroImage. 2011;55:1024–33. A prospective cross-sectional study of 14 chronic cervical SCI patients and 14 age-matched controls, showing significant differences in fractional anisotropy, magnetization transfer ratio, and cord area in otherwise healthy appearing areas of the rostral spinal cord.

Cadotte DW, Bosma R, Mikulis D, et al. Plasticity of the injured human spinal cord: insights revealed by spinal cord functional MRI. PLoS One. 2012;7, e45560. A prospective cross-sectional cohort study of 18 chronic SCI patients and 20 healthy controls, employing functional MRI of the spinal cord comparing thermal stimulation in normal and abnormal dermatomes to controls, showing differences between incomplete SCI patients and controls ( p  = 0.025) and an inverse relationship between sensory impairment and number of activated voxels in abnormal dermatomes ( R 2  = 0.93, p  < 0.001).

American Association of Neurological Surgeons (AANS). Management of acute spinal cord injuries in an intensive care unit or other monitored setting. Neurosurgery. 2002;50(Suppl 3):S51–7.

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ClinicalTrials.gov Website. Mean arterial blood pressure treatment for acute spinal cord injury (MAPS). http://www.clinicaltrial.gov/ct2/show/NCT02232165. Accessed November 20, 2014.

Dvorak MF, Noonan VK, Fallah N, et al. The influence of time from injury to surgery on motor recovery and length of hospital stay in acute traumatic spinal cord injury: an observational Canadian cohort study. J Neurotrauma. 2014. A retrospective observational analysis of 1410 Canadian SCI patients that demonstrates that early decompression (<24 h) confers improved motor recovery of 6.3 ASIA motor points in AIS B, C, and D patients, and decreases length of stay in AIS A and B patients.

Wilson JR, Singh A, Craven C, et al. Early versus late surgery for traumatic spinal cord injury: the results of a prospective Canadian cohort study. Spinal Cord. 2012;50:840–3. A multi-center prospective Canadian cohort study of 84 patients that decompressive surgery within 24 h increases the chances of a 2-grade AIS improvement (p = 0.01) and increased ASIA motor score (after adjustments for pre-operative status and neurological level, p  = 0.01).

Furlan JC, Noonan V, Cadotte DW, Fehlings MG. Timing of decompressive surgery of spinal cord after traumatic spinal cord injury: an evidence-based examination of pre-clinical and clinical studies. J Neurotrauma. 2011;28:1371–99.

ClinicalTrials.gov website. Surgical treatment for spinal cord injury (SCI-POEM). http://www.clinicaltrial.gov/ct2/show/NCT01674764. Accessed November 20, 2014.

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Bracken MB. Steroids for acute spinal cord injury. Cochrane Database Syst Rev. 2012;1, CD001046. Pooled results of 6 RCTs show no overall neurological benefit of methylprednisolone, but subgroup analysis demonstrated a 4-point improvement on ASIA motor score with 24-h MP administration initiated within 8 h. The data also showed doubling of wound infection and gastrointestinal bleeding rates, but a converse trend toward decreased mortality.

Grossman RG, Fehlings MG, Frankowski RF, et al. A prospective, multicenter, phase I matched-comparison group trial of safety, pharmacokinetics, and preliminary efficacy of riluzole in patients with traumatic spinal cord injury. J Neurotrauma. 2014;31:239–55. A prospective cohort study of oral Riluzole in 36 patients with acute SCI showing the cervical subgroup (n = 28) improved 15.5 points more than a matched registry control group (p = 0.02), but no benefit in thoracic SCI (n = 8). Riluzole showed similar rates of medical complications, although mild–moderate increases in various hepatic enzymes and bilirubin were seen in 14–70% of patients.

ClinicalTrials.gov website. Riluzole in Spinal Cord Injury (RISCIS) trial. http://clinicaltrials.gov/show/NCT01597518. Accessed November 20, 2014.

Casha S, Zygun D, McGowan MD, et al. Results of a phase II placebo-controlled randomized trial of minocycline in acute spinal cord injury. Brain. 2012;135:1224–36. A single-center placebo-controlled RCT in 44 SCI patients, showing a weak trend toward improvement on ASIA motor scores (6 points, n  = 44, p  = 0.20), but the cervical subgroup showed improvement approaching significance (14 points, n  = 25, p  = 0.05). One event of transient hepatic enzyme elevation was observed.

ClinicalTrials.gov website. Minocycline in acute spinal cord injury (MASC). http://www.clinicaltrial.gov/ct2/show/NCT01828203. Accessed November 21, 2014.

Takahashi H, Yamazaki M, Okawa A, et al. Neuroprotective therapy using granulocyte colony-stimulating factor for acute spinal cord injury: a phase I/IIa clinical trial. Eur Spine J. 2012;21:2580–7. A phase I/IIa trial of intravenous injection in 16 humans demonstrated safety, and all 16 patients showed improvement in AIS grade.

Inada T, Takahashi H, Yamazaki M, et al. Multicenter prospective nonrandomized controlled clinical trial to prove neurotherapeutic effects of granulocyte colony-stimulating factor for acute spinal cord injury: analysis of follow-up cases after at least 1 year. Spine. 2014;39:213–9. A multi-center non-randomized controlled study (controls at a different institution than G-CSF subjects), with 15 of 17 subjects receiving G-CSF improving at least one AIS grade.

ClinicalTrials.gov website. Study to evaluate the efficacy, safety, and pharmacokinetics of SUN13837 injection in adult subjects with acute spinal cord injury (ASCI). http://www.clinicaltrial.gov/ct2/show/NCT02260713. Accessed November 21, 2014.

ClinicalTrials.gov website. A phase 2 double-blind, randomized, placebo-controlled study to determine the safety, tolerability and potential activity of AC105 following a regimen of 6 doses over 30 hours in patients with acute traumatic spinal cord injury (SCI) as compared to patients treated with placebo. http://clinicaltrials.gov/ct2/show/NCT01750684. Accessed November 20, 2014.

Fehlings MG, Theodore N, Harrop J, et al. A phase I/IIa clinical trial of a recombinant Rho protein antagonist in acute spinal cord injury. J Neurotrauma. 2011;28:787–96. A phase I/IIa study in 48 cervical and thoracic SCI patients that used escalating doses demonstrated no motor improvement in thoracic cases, but cervical patients ( n  = 16) improved 18.6 (±19.3) points in ASIA motor score, showing a trend toward better recovery than the 10 points expected from historic controls.

ClinicalTrials.gov website. Cethrin in Acute Cervical Spinal Cord Injury (CACSCI) trial. http://clinicaltrials.gov/ct2/show/NCT02053883. Accessed November 20, 2014.

ClinicalTrials.gov website. The rho-inhibitor ibuprofen for the treatment of acute spinal cord injury: investigation of safety, feasibility and pharmacokinetics. http://www.clinicaltrial.gov/ct2/show/NCT02096913. Accessed November 20, 2014.

ClinicalTrials.gov website. Acute safety, tolerability, feasibility and pharmacokinetics of intrath. administered ATI355 in patients with acute SCI. http://clinicaltrials.gov/show/NCT00406016. Accessed November 21, 2014.

ClinicalTrials.gov website. A phase I/II study to evaluate the safety and efficacy of intrathecal injection of KP-100IT in subjects with acute spinal cord injury. http://www.clinicaltrial.gov/ct2/show/NCT02193334. Accessed November 20, 2014.

Lammertse DP, Jones LA, Charlifue SB, et al. Autologous incubated macrophage therapy in acute, complete spinal cord injury: results of the phase 2 randomized controlled multicenter trial. Spinal Cord. 2012;50:661–71.

ClinicalTrials.gov website. Autologous bone marrow cell transplantation in persons with acute spinal cord injury—an Indian pilot study. http://www.clinicaltrial.gov/ct2/show/NCT02260713. Accessed November 21, 2014.

ClinicalTrials.gov website. Study of human central nervous system (CNS) stem cell transplantation in cervical spinal cord injury. http://clinicaltrials.gov/ct2/show/NCT02163876. Accessed November 21, 2014.

ClinicalTrials.gov website. Transplantation of autologous adipose derived stem cells (ADSCs) in spinal cord injury treatment. http://www.clinicaltrial.gov/ct2/show/NCT02034669. Accessed November 20, 2014.

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Lo TP, Cho K-S, Garg MS, et al. Systemic hypothermia improves histological and functional outcome after cervical spinal cord contusion in rats. J Comp Neurol. 2009;514:433–48.

Dietrich WD, Levi AD, Wang M, Green BA. Hypothermic treatment for acute spinal cord injury. Neurotherapeutics. 2011;8:229–39. A case–control study of 14 AIS A patients undergoing induced moderate hypothermia (33C) via intravascular cooling compared with matched controls, showing no difference in complication rates and 6/14 (43%) hypothermia subjects converting to incomplete injury compared with 3/14 (21%) controls (non-significant).

ClinicalTrials.gov website. Efficacy of intravenously instituted hypothermia treatment in improving functional outcomes in patients following acute spinal cord injury. http://www.clinicaltrial.gov/ct2/show/NCT01739010. Accessed November 20, 2014.

Fehlings MG, Wilson JR, Cho N. Methylprednisolone for the treatment of acute spinal cord injury: counterpoint. Neurosurgery. 2014;61:36–42.

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