Time is spine: a review of translational advances in spinal cord injury

Abstract

Acute traumatic spinal cord injury (SCI) is a devastating event with far-reaching physical, emotional, and economic consequences for patients, families, and society at large. Timely delivery of specialized care has reduced mortality; however, long-term neurological recovery continues to be limited. In recent years, a number of exciting neuroprotective and regenerative strategies have emerged and have come under active investigation in clinical trials, and several more are coming down the translational pipeline. Among ongoing trials are RISCIS (riluzole), INSPIRE (Neuro-Spinal Scaffold), MASC (minocycline), and SPRING (VX-210). Microstructural MRI techniques have improved our ability to image the injured spinal cord at high resolution. This innovation, combined with serum and cerebrospinal fluid (CSF) analysis, holds the promise of providing a quantitative biomarker readout of spinal cord neural tissue injury, which may improve prognostication and facilitate stratification of patients for enrollment into clinical trials. Given evidence of the effectiveness of early surgical decompression and growing recognition of the concept that "time is spine," infrastructural changes at a systems level are being implemented in many regions around the world to provide a streamlined process for transfer of patients with acute SCI to a specialized unit. With the continued aging of the population, central cord syndrome is soon expected to become the most common form of acute traumatic SCI; characterization of the pathophysiology, natural history, and optimal treatment of these injuries is hence a key public health priority. Collaborative international efforts have led to the development of clinical practice guidelines for traumatic SCI based on robust evaluation of current evidence. The current article provides an in-depth review of progress in SCI, covering the above areas.

Keywords: AIS = ASIA Impairment Scale; ASIA = American Spinal Injury Association; AUC = area under the curve; BSCB = blood–spinal cord barrier; CCS = central cord syndrome; CELLTOP = Adipose Stem Cells for Traumatic Spinal Cord Injury; CNS = central nervous system; CSF = cerebrospinal fluid; CSPG = chondroitin sulfate proteoglycan; CST = corticospinal tract; Cmax = maximum concentration; DTI = diffusion tensor imaging; ESC = embryonic stem cell; FES = functional electrical stimulation; FIM = Functional Independence Measure; G-CSF = granulocyte colony stimulating factor; GFAP = glial fibrillary acidic protein; GRASSP = Graded Redefined Assessment of Strength Sensibility and Prehension; HAMC = hyaluronan/methylcellulose; HGF = hepatocyte growth factor; IL = interleukin; IV = intravenous; MASC = Minocycline in Acute Spinal Cord Injury; MCP = monocyte chemotactic protein; MPSS = methylprednisolone sodium succinate; MSC = mesenchymal stem cell; MT = magnetization transfer; MTR = MT ratio; NSC = neural stem cell; OEC = olfactory ensheathing cell; OPC = oligodendrocyte progenitor cell; RCT = randomized controlled trial; RISCIS = Riluzole in Acute Spinal Cord Injury Study; SCI = spinal cord injury; SCIM = Spinal Cord Independence Measure; SCING = Spinal Cord Injury Neuroprotection with Glyburide; STASCIS = Surgical Timing in Acute Spinal Cord Injury Study; TNF = tumor necrosis factor; Tmax = time to Cmax; aFGF = acidic fibroblast growth factor; bFGF = basic fibroblast growth factor; clinical trial; guideline; neuroprotection; neuroregeneration; spinal cord injury; stem cell.