Traumatic spinal cord injury treatment

Traumatic spinal cord injury (tSCI) is a life-changing and potentially overwhelming event. The sudden disruption of the spinal cord's integrity necessitates rapid attention at a specialized medical center, and involves a multilateral collaboration between neurologists, spine surgeons, critical care physicians, and trauma specialists. Even with care under ideal conditions, many tSCI patients have a significant disability that persists for the rest of their lives. However, recently, we have seen a proliferation in clinical and translational trials that offer the promise that new treatments may be available soon 1).

Clinical management in the acute setting needs to occur in the intensive care unit in order to identify, prevent, and treat secondary insults from local ischemia, hypotension, hypoxia, and inflammation. Maintenance of adequate perfusion and oxygenation is quintessential and a mean arterial pressure >85-90 mm Hg should be kept for at least 1 week. A cervical collar and full spinal precautions (log-roll, flat, holding C-spine) should be maintained until the spinal column has been fully evaluated by a spine surgeon. In patients with SCI, there is a high incidence of other bodily injuries, and there should be a low threshold to assess for visceral, pelvic, and long bone injuries. Computed tomography of the spine is superior to plain films, as the former rarely misses fractures, though caution needs to be exerted as occipitocervical dislocation can still be missed. To reliably assess the spinal neural elements, soft tissues, and ligamentous structures, magnetic resonance imaging is indicated and should be obtained within 48-72 h from the time of injury. All patients should be graded daily using the American Spinal Injury Association classification, with the first prognostic score at 72 h postinjury. Patients with high cervical cord (C4 or higher) injury should be intubated immediately, and those with lower cord injuries should be evaluated on a case-by-case basis. However, in the acute setting, respiratory mechanics will be disrupted with any spinal cord lesion above T11. Steroids have become extremely controversial, and the professional societies for neurosurgery in the United States have given a level 1 statement against their use in all patients. Grant et al. therefore, do not advocate for them at this time. With every SCI, a spine surgeon must be consulted to discuss operative vs nonoperative management strategies. Indications for surgery include a partial or progressive neurologic deficit, instability of the spine not allowing for mobilization, correction of a deformity, and prevention of potential neurologic compromise. Measures to prevent pulmonary emboli from deep venous thromboembolisms are necessary: IVC filters are recommended in bedbound patients and low-molecular weight heparins are superior to unfractionated heparin. Robust prevention of pressure ulcers as well as nutritional support should be a mainstay of treatment. Lastly, it is important to note that neurologic recovery is a several-year process. The most recovery occurs in the first year following injury, and therefore aggressive rehabilitation is crucial 2).

Early decompression surgery post-SCI can enhance patient outcomes, but does not directly facilitate neural repair and regeneration. Currently, there are no U.S. Food and Drug Administration-approved pharmacological therapies to augment motor function and functional recovery in individuals with traumatic SCI.

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 study (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 3).

Minocycline-Loaded Poly(α-Lipoic Acid)-Methylprednisolone Prodrug Nanoparticles can mitigate secondary inflammation and preserve motor function following experimental TSCI, which suggests their potential for clinical application 4).

Huang KT, Lu Y. Traumatic Spinal Cord Disorders: Current Topics and Future Directions. Semin Neurol. 2021 May 19. doi: 10.1055/s-0041-1725125. Epub ahead of print. PMID: 34010969.
Grant RA, Quon JL, Abbed KM. Management of acute traumatic spinal cord injury. Curr Treat Options Neurol. 2015 Feb;17(2):334. doi: 10.1007/s11940-014-0334-1. PMID: 25630995.
Badhiwala JH, Ahuja CS, Fehlings MG. Time is spine: a review of translational advances in spinal cord injury. J Neurosurg Spine. 2018 Dec 20;30(1):1-18. doi: 10.3171/2018.9.SPINE18682. Review. PubMed PMID: 30611186.
Lin F, Liu Y, Luo W, Liu S, Wang Y, Gu R, Liu W, Xiao C. Minocycline-Loaded Poly(α-Lipoic Acid)-Methylprednisolone Prodrug Nanoparticles for the Combined Anti-Inflammatory Treatment of Spinal Cord Injury. Int J Nanomedicine. 2022 Jan 7;17:91-104. doi: 10.2147/IJN.S344491. PMID: 35027828; PMCID: PMC8752067.
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