Christopher S. Ahuja

BACKGROUND: Traumatic spinal cord injuries (SCI) have devastating consequences for the physical, financial, and psychosocial well-being of patients and their caregivers. Expediently delivering interventions during the early postinjury period can have a tremendous impact on long-term functional recovery. PATHOPHYSIOLOGY: This is largely due to the unique pathophysiology of SCI where the initial traumatic insult (primary injury) is followed by a progressive secondary injury cascade characterized by ischemia, proapoptotic signaling, and peripheral inflammatory cell infiltration. Over the subsequent hours, release of proinflammatory cytokines and cytotoxic debris (DNA, ATP, reactive oxygen species) cyclically adds to the harsh postinjury microenvironment. As the lesions mature into the chronic phase, regeneration is severely impeded by the development of an astroglial-fibrous scar surrounding coalesced cystic cavities. Addressing these challenges forms the basis of current and upcoming treatments for SCI. MANAGEMENT: This paper discusses the evidence-based management of a patient with SCI while emphasizing the importance of early definitive care. Key neuroprotective therapies are summarized including surgical decompression, methylprednisolone, and blood pressure augmentation. We then review exciting neuroprotective interventions on the cusp of translation such as Riluzole, Minocycline, magnesium, therapeutic hypothermia, and CSF drainage. We also explore the most promising neuroregenerative strategies in trial today including Cethrin™, anti-NOGO antibody, cell-based approaches, and bioengineered biomaterials. Each section provides a working knowledge of the key preclinical and patient trials relevant to clinicians while highlighting the pathophysiologic rationale for the therapies. CONCLUSION: We conclude with our perspectives on the future of treatment and research in this rapidly evolving field.

CONTEXT: Spinal cord injury (SCI) is a devastating condition that can lead to significant neurological impairment and reduced quality of life. Despite advancements in our understanding of the pathophysiology and secondary injury mechanisms involved in SCI, there are currently very few effective treatments for this condition. The field, however, is rapidly changing as new treatments are developed and key discoveries are made. METHODS: In this review, we outline the pathophysiology, management, and long-term rehabilitation of individuals with traumatic SCI. We also provide an in-depth overview of emerging therapies along the spectrum of the translational pipeline. EVIDENCE SYNTHESIS: The concept of "time is spine" refers to the concept which emphasizes the importance of early transfer to specialized centers, early decompressive surgery, and early delivery of other treatments (e.g. blood pressure augmentation, methylprednisolone) to affect long-term outcomes. Another important evolution in management has been the recognition and prevention of the chronic complications of SCI including respiratory compromise, bladder dysfunction, Charcot joints, and pressure sores through directed interventions along with early integration of physical rehabilitation and mobilization. There have also been significant advances in neuroprotective and neuroregenerative strategies for SCI, many of which are actively in clinical trial including riluzole, Cethrin, stem cell transplantation, and the use of functional electrical stimulation. CONCLUSION: Pharmacologic treatments, cell-based therapies, and other technology-driven interventions will likely play a combinatorial role in the evolving management of SCI as the field continues to evolve.

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.