. 2017 Sep 5;7(3 Suppl):116S–137S. doi: 10.1177/2192568217706366

Table 2.

Overview of Previous Systematic Reviews of MPSS vs Control (Placebo or no MPSS) in the Treatment of Acute Spinal Cord Injury.

Assessment (Year)	Literature Search Dates	Purpose	Inclusion Criteria	Evidence Base Available^a,b	Follow-up Range	Primary Conclusions	AMSTAR Score^c
Short (2000)³⁵	1966 to December 1999	To summarize the evidence evaluating the effect of high-dose MPSS on neurological improvement following acute SCI	Inclusion: High-dose MPSS or equivalent dexamethasone given ≤12 hours of SCI Outcome measures reported separately for steroid and non-steroid groups Exclusion: Questionable study validity	3 RCTs, 6 nonrandomized studies (N = 1018)^b	24 hours to 4+ years	Efficacy: The evidence produced by this systematic review does not support the use of high-dose MPSS in acute SCI to improve neurological recovery. Safety: A deleterious effect on early mortality and morbidity cannot be excluded by this evidence. Economic: Not addressed	4/11; medium quality
Hurlbert (2001)³⁶	NR	To review available literature and formulate evidence-based recommendations for the use of MPSS in acute SCI	NR	5 RCTs, 3 retrospective cohorts, 1 case-control (N = 2455)	2 months to 30 months	Efficacy: All studies failed to demonstrate improvement from steroid administration in any of the a priori hypotheses tested; MPSS cannot be recommended for routine use in acute nonpenetrating SCI. Safety: Prolonged administration of high-dose steroids (48 hours) may be harmful. Economic: Not addressed	2/11; low quality
Hugenholtz (2002)³⁷	MEDLINE January 1, 1966, to April 2001 CINAHL 1982-2001 HealthSTAR 1990-2000	To address controversy surrounding the use of MPSS infusion after acute SCI	Inclusion: Acute SCI MPSS Clinical trials (randomized or nonrandomized) Exclusion: Articles confined to a pediatric population Gunshot or open SCI Nontraumatic SCI Animal experiments Nonsteriod therapy Articles that did not address clinical data	3 RCTs, 5 nonrandomized studies, 1 review (N = 3169)	6 weeks to 1 year	Efficacy: There is insufficient evidence to support the use of high-dose MPSS within 8 hours following an acute closed SCI as a treatment standard or as a guideline for treatment. MPSS, prescribed as a bolus IV infusion of 30 mg/kg of body weight over 15 minutes within 8 hours of closed SCI, followed 45 minutes later by an infusion of 5.4 mg/kg of body weight per hour for 23 hours, is a treatment option with weak clinical evidence (Level I to II-1). There is insufficient evidence to support extending MPSS infusion beyond 23 hours if chosen as a treatment option. Safety: In well-designed studies, there are no statistically significant complications to MPSS therapy; there are, however, trends to increased sepsis and hyperglycemia. Economic: The NASCIS II and III protocols would cost $322.02 and $579.32, respectively, per patient. Nursing time and equipment costs are not included.	4/11; medium quality
Sayer (2006)³⁸	NR	To summarize the evidence evaluating the use of MPSS in acute SCI	NR	3 RCTs, 6 nonrandomized studies (N = 2173)	6 weeks to 2+ years	Efficacy: There is insufficient evidence to support the use of MPSS as a standard treatment in acute SCI. Safety: MPSS use is associated with increased risk of infections. Economic: Not addressed	2/11; low quality
Botelho (2009)³⁹	MEDLINE, LILACS, and EMBASE	To review RCTs evaluating the use of MPSS compared with placebo for SCI	Inclusion: Randomized trials of patients with traumatic SCI Exclusion: Studies examining spinal trauma without SCI Studies examining victims of whiplash injury without neurological damage	2 RCTs (3 reports) (N = 533)	6 months to 1 year	Efficacy: The results do not suggest clinical benefits of MPSS due to only modest differences between treatment strategies. Safety: The use of MPSS is associated with an increased risk of pulmonary complications and gastrointestinal bleeding in patients aged approximately 60 years. Economic: Not addressed	6/11; medium quality
Bracken (2012)³⁰	Through August 2011	To assess the effects of steroids in patients with acute SCI	Inclusion: RCTs including patients with: Acute spinal cord injury Whiplash, lumbar disc disease Steroid treatment Exclusion: NR	3 RCTs (6 reports), 5 non-RCTs (N = 1660)	2 weeks to 1 year	Efficacy: MPSS enhances neurologic recovery if therapy is started within 8 hours of injury by using an initial bolus of 30 mg/kg by IV for 15 minutes, followed 45 minutes later by a continuous infusion of 5.4 mg/kg/h for 24 hours. Safety: Not addressed Economic: Not addressed	9/11; high quality
Hurlbert (2013)⁹	1966-2011	To build upon a medical evidence-based guideline on the use of MPSS and GM-1 Ganglioside previously published by the AANS and CNS	Inclusion: NR Exclusion: Non-English or nonhuman Case reports Pharmacokinetic reports General reviews Editorials Critiques Manuscripts without original data	6 RCTs (9 reports), 14 nonrandomized studies (N = 14 138)	2 weeks to 1 year	Efficacy: There is no Class I or II medical evidence suggesting any beneficial effect of MPSS in an acute SCI population; however, Class III medical evidence has supported the neuroprotective effect of MPSS. Safety: Class I, II, and III evidence suggests that high-dose steroids are associated with harmful side effects including death. Economic: Not addressed	2/11; low quality

Abbreviations: AANS, American Association of Neurological Surgeons; CINAHL, Current Index to Nursing and Allied Health Literature; CNS, Congress of Neurological Surgeons; EMBASE, Excerpta Medical Database; HealthSTAR, Health Services Technology, Administration, and Research; LILACS, Literatura Latino Americana em Ciências da Saúde; MEDLINE, Medical Literature Analysis and Retrieval System Online; MPSS, methylprednisolone sodium succinate; N/A, not available; NASCIS, National Acute Spinal Cord Injury Study; NR, not reported; RCT, randomized controlled trial; SCI, spinal cord injury.

^aThe NASCIS RCTs were published as multiple reports with different follow-up times.

^bShort (2000): Included 2 studies with penetrating spinal cord injury (gunshot).

^cAssessment of Multiple Systematic Reviews evaluation tool: high quality, 8 to 11; medium quality, 4 to 7; low quality, 0 to 3.