Advance in pediatric spinal cord injury

Abstract

The incidence rate of spinal cord injury in children is lower than that in adults, accounting for about 5% of all spinal cord injuries. Motor vehicle accidents are the main cause of spinal cord injuries in children. As the spine of children is still in the process of growth and development, the anatomical structure and biomechanics have unique characteristics, and its etiology, injury site, and clinical manifestations are different from those of adults. Misdiagnosis and delayed diagnosis can lead to severe spinal deformity and neurological complications. Children and adolescents with spinal cord injuries may suffer from lifelong disability, which will do great harm to children, families, and society. Early magnetic resonance imaging examination can effectively avoid underdiagnosis of spinal cord injury without radiographic abnormality and select appropriate treatment. In addition, it is also important to establish a family-centered rehabilitation model to help the affected children reintegrate into society and achieve the goal of returning to normal life. This article reviews the etiology, epidemiology, clinical characteristics, complications, and treatment of spinal cord injury in children and adolescents.

Keywords

pediatric spinal cord injury / SCIWORA / spinal cord injury / spine

References

[1] McDonald JW, Sadowsky C. Spinal-cord injury. Lancet. 2002;359(9304):417-425.

[2] Fan B, Wei Z, Yao X, et al. Microenvironment imbalance of spinal cord injury. Cell Transpl. 2018;27(6):853-866.

[3] Schanne FA, Kane AB, Young EE, Farber JL. Calcium dependence of toxic cell death: a final common pathway. Science. 1979;206(4419):700-702.

[4] Hellenbrand DJ, Quinn CM, Piper ZJ, et al. The secondary injury cascade after spinal cord injury: an analysis of local cytokine/chemokine regulation. Neural Regen Res. 2024;19(6):1308-1317.

[5] Liu M, Wu W, Li H, et al. Necroptosis, a novel type of programmed cell death, contributes to early neural cells damage after spinal cord injury in adult mice. J Spinal Cord Med. 2015;38(6):745-753.

[6] Wang Y, Wang H, Tao Y, Zhang S, Wang J, Feng X. Necroptosis inhibitor necrostatin-1 promotes cell protection and physiological function in traumatic spinal cord injury. Neuroscience. 2014;266:91-101.

[7] Tian T, Zhang S, Yang M. Recent progress and challenges in the treatment of spinal cord injury. Protein Cell. 2023;14(9):635-652.

[8] Yip PK, Malaspina A. Spinal cord trauma and the molecular point of no return. Mol Neurodegener. 2012;7:6.

[9] Al Mamun A, Wu Y, Monalisa I, et al. Role of pyroptosis in spinal cord injury and its therapeutic implications. J Adv Res. 2021;28:97-109.

[10] Chen M, Zheng B. Axon plasticity in the mammalian central nervous system after injury. Trends Neurosci. 2014;37(10):583-593.

[11] Huntemer-Silveira A, Patil N, Brickner MA, Parr AM. Strategies for oligodendrocyte and myelin repair in traumatic CNS injury. Front Cell Neurosci. 2020;14:619707.

[12] Bravar G, Luchesa Smith A, Siddiqui A, Lim M. Acute myelopathy in childhood. Children. 2021;8(11):1055.

[13] Caffarelli C, Santamaria F, Santoro A, et al. Best practices, challenges and innovations in pediatrics in 2019. Ital J Pediatr. 2020;46(1):176.

[14] Cunha NSC, Malvea A, Sadat S, Ibrahim GM, Fehlings MG. Pediatric spinal cord injury: a review. Children (Basel). 2023;10(9):1456.

[15] Zou Z, Teng A, Huang L, et al. Pediatric spinal cord injury without radiographic abnormality: the Beijing experience. Spine (Phila Pa 1976). 2021;46(20):E1083-E1088.

[16] Eleraky MA, Theodore N, Adams M, Rekate HL, Sonntag VK. Pediatric cervical spine injuries: report of 102 cases and review of the literature. J Neurosurg. 2000;92(1 Suppl l):12-17.

[17] Poorman GW, Segreto FA, Beaubrun BM, et al. Traumatic fracture of the pediatric cervical spine: etiology, epidemiology, concurrent injuries, and an analysis of perioperative outcomes using the kids' inpatient database. Internet J Spine Surg. 2019;13(1):68-78.

[18] Alexiades NG, Parisi F, Anderson RCE. Pediatric spine trauma: a brief review. Neurosurgery. 2020;87(1):E1-E9.

[19] Alas H, Pierce KE, Brown A, et al. Sports-related cervical spine fracture and spinal cord injury: a review of nationwide pediatric trends. Spine (Phila Pa. 2021;46(1):22-28.

[20] Zebracki K, Melicosta M, Unser C, Vogel LC. A primary care provider's guide to pediatric spinal cord injuries. Top Spinal Cord Inj Rehabil. 2020;26(2):91-99

[21] Vogel LC, Anderson CJ. Spinal cord injuries in children and adolescents: a review. J Spinal Cord Med. 2003;26(3):193-203.

[22] Benmelouka A, Shamseldin LS, Nourelden AZ, Negida A. A review on the etiology and management of pediatric traumatic spinal cord injuries. Adv J Emerg Med. 2020;4(2):e28.

[23] Huisman T, Phelps T, Bosemani T, Tekes A, Poretti A. Parturitional injury of the head and neck. J Neuroimaging. 2015;25(2):151-166.

[24] Achildi O, Betz RR, Grewal H. Lapbelt injuries and the seatbelt syndrome in pediatric spinal cord injury. J Spinal Cord Med. 2007;30((Suppl 1)):S21-S24.

[25] Carroll T, Smith CD, Liu X, et al. Spinal cord injuries without radiologic abnormality in children: a systematic review. Spinal Cord. 2015;53(12):842-848.

[26] Pang D, Wilberger JE, Jr. Spinal cord injury without radiographic abnormalities in children. J Neurosurg. 1982;57(1):114-129.

[27] Wang JZ, Yang M, Meng M, Li ZH. Clinical characteristics and treatment of spinal cord injury in children and adolescents. Chin J Traumatol. 2023;26(1):8-13.

[28] Rozzelle CJ, Aarabi B, Dhall SS, et al. Spinal cord injury without radiographic abnormality (SCIWORA). Neurosurgery. 2013;72(Suppl 2):227-233.

[29] Schottler J, Vogel LC, Sturm P. Spinal cord injuries in young children: a review of children injured at 5 years of age and younger. Dev Med Child Neurol. 2012;54(12):1138-1143.

[30] Zhu F, Liu Y, Zeng L, et al. Evaluating the severity and prognosis of acute traumatic cervical spinal cord injury: a novel classification using diffusion tensor imaging and diffusion tensor tractography. Spine (Phila Pa 1976). 2021;46(10):687-694.

[31] Iaconis Campbell J, Coppola F, Volpe E, Salas Lopez E. Thoracic spinal cord injury without radiologic abnormality in a pediatric patient case report. J Surg Case Rep. 2018;2018(10):rjy250.

[32] Copley PC, Tilliridou V, Kirby A, Jones J, Kandasamy J. Management of cervical spine trauma in children. Eur J Trauma Emerg Surg. 2019;45(5):777-789.

[33] Caine DJ, Young K, Provance AJ. Pediatric and adolescent injury in mountain biking. Res Sports Med. 2018;26(Suppl 1):71-90.

[34] Piatt J, Imperato N. Epidemiology of spinal injury in childhood and adolescence in the United States: 1997-2012. J Neurosurg Pediatr. 2018;21(5):441-448

[35] McCarthy JJ, Betz RR. Hip disorders in children who have spinal cord injury. Orthop Clin N Am. 2006;37(2):197-202.

[36] Hickey KJ, Vogel LC, Willis KM, Anderson CJ. Prevalence and etiology of autonomic dysreflexia in children with spinal cord injuries. J Spinal Cord Med. 2004;27(Suppl 1):S54-S60.

[37] Consortium for Spinal Cord M. Acute management of autonomic dysreflexia: individuals with spinal cord injury presenting to health-care facilities. J Spinal Cord Med. 2002;25(Suppl 1):S67-S88.

[38] Powell A, Davidson L. Pediatric spinal cord injury: a review by organ system. Phys Med Rehabil Clin. 2015;26(1):109-132.

[39] Zidek K, Srinivasan R. Rehabilitation of a child with a spinal cord injury. Semin Pediatr Neurol. 2003;10(2):140-150.

[40] Minisola S, Pepe J, Piemonte S, Cipriani C. The diagnosis and management of hypercalcaemia. BMJ. 2015;350:h2723.

[41] Rekate HL, Theodore N, Sonntag VK, Dickman CA. Pediatric spine and spinal cord trauma. State of the art for the third millennium. Childs Nerv Syst. 1999;15(11-12):743-750.

[42] Anjum A, Yazid MD, Fauzi Daud M, et al. Spinal cord injury: pathophysiology, multimolecular interactions, and underlying recovery mechanisms. Int J Mol Sci. 2020;21(20):7533.

[43] Hurlbert RJ, Hadley MN, Walters BC, et al. Pharmacological therapy for acute spinal cord injury. Neurosurgery. 2013;72(Suppl 2):93-105.

[44] Tsutsumi S, Ueta T, Shiba K, Yamamoto S, Takagishi K. Effects of the Second National Acute Spinal Cord Injury Study of high-dose methylprednisolone therapy on acute cervical spinal cord injury-results in spinal injuries center. Spine (Phila Pa 1976). 2006;31(26):2992-2996.

[45] Bracken MB, Shepard MJ, Holford TR, et al. Methylprednisolone or tirilazad mesylate administration after acute spinal cord injury: 1-year follow up. Results of the third National Acute Spinal Cord Injury randomized controlled trial. J Neurosurg. 1998;89(5):699-706.

[46] Rouanet C, Reges D, Rocha E, Gagliardi V, Silva GS. Traumatic spinal cord injury: current concepts and treatment update. Arq Neuropsiquiatr. 2017;75(6):387-393.

[47] Bracken MB, Shepard MJ, Collins WF, et al. A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the Second National Acute Spinal Cord Injury Study. N Engl J Med. 1990;322(20):1405-1411.

[48] Cage JM, Knox JB, Wimberly RL, Shaha S, Jo C, Riccio AI. Complications associated with high-dose corticosteroid administration in children with spinal cord injury. J Pediatr Orthop. 2015;35(7):687-692.

[49] Griffin JM, Bradke F. Therapeutic repair for spinal cord injury: combinatory approaches to address a multifaceted problem. EMBO Mol Med. 2020;12(3):e11505.

[50] Casha S, Zygun D, McGowan MD, Bains I, Yong VW, Hurlbert RJ. Results of a phase II placebo-controlled randomized trial of minocycline in acute spinal cord injury. Brain. 2012;135(Pt 4):1224-1236.

[51] Liu Z, Yang Y, He L, et al. High-dose methylprednisolone for acute traumatic spinal cord injury: a meta-analysis. Neurology. 2019;93(9):e841-e850.

[52] Karsy M, Hawryluk G. Modern medical management of spinal cord injury. Curr Neurol Neurosci Rep. 2019;19(9):65.

[53] Consortium for Spinal Cord M. Early acute management in adults with spinal cord injury: a clinical practice guideline for health-care professionals. J Spinal Cord Med. 2008;31(4):403-479.

[54] Kirshblum SC, Burns SP, Biering-Sorensen F, et al. International standards for neurological classification of spinal cord injury (revised 2011). J Spinal Cord Med. 2011;34(6):535-546.

[55] Srinivasan V, Jea A. Pediatric thoracolumbar spine trauma. Neurosurg Clin. 2017;28(1):103-114.

[56] Goldstein HE, Anderson RC. Classification and management of pediatric craniocervical injuries. Neurosurg Clin. 2017;28(1):73-90.

[57] Hadley MN, Zabramski JM, Browner CM, Rekate H, Sonntag VK. Pediatric spinal trauma. Review of 122 cases of spinal cord and vertebral column injuries. J Neurosurg. 1988;68(1):18-24.

[58] Sayama C, Chen T, Trost G, Jea A. A review of pediatric lumbar spine trauma. Neurosurg Focus. 2014;37(1):E6.

[59] Gavira N, Amelot A, Cook AR, Hamel A, Buffenoir K, Cristini J. Thoracolumbar spinal fracture in children: conservative or surgical treatment?Neurochirurgie. 2022;68(3):309-314.

[60] Ursavas S, Darici H, Karaoz E. Olfactory ensheathing cells: unique glial cells promising for treatments of spinal cord injury. J Neurosci Res. 2021;99(6):1579-1597.

[61] Yu F, Li P, Du S, et al. Olfactory ensheathing cells seeded decellularized scaffold promotes axonal regeneration in spinal cord injury rats. J Biomed Mater Res. 2021;109(5):779-787

[62] Monje PV, Deng L, Xu XM. Human Schwann cell transplantation for spinal cord injury: prospects and challenges in translational medicine. Front Cell Neurosci. 2021;15:690894.

[63] Hill CE, Moon LD, Wood PM, Bunge MB. Labeled Schwann cell transplantation: cell loss, host Schwann cell replacement, and strategies to enhance survival. Glia. 2006;53(3):338-343.

[64] Fu H, Hu D, Chen J, et al. Repair of the injured spinal cord by Schwann cell transplantation. Front Neurosci. 2022;16:800513.

[65] Cofano F, Boido M, Monticelli M, et al. Mesenchymal stem cells for spinal cord injury: current options, limitations, and future of cell therapy. Int J Mol Sci. 2019;20(11):2698.

[66] Lu P, Blesch A, Graham L, et al. Motor axonal regeneration after partial and complete spinal cord transection. J Neurosci. 2012;32(24):8208-8218.

[67] Chen WC, Liu WF, Bai YY, et al. Transplantation of mesenchymal stem cells for spinal cord injury: a systematic review and network meta-analysis. J Transl Med. 2021;19(1):178.

[68] Gilbert EAB, Lakshman N, Lau KSK, Morshead CM. Regulating endogenous neural stem cell activation to promote spinal cord injury repair. Cells. 2022;11(5):846.

[69] de Freria CM, Van Niekerk E, Blesch A, Lu P. Neural stem cells: promoting axonal regeneration and spinal cord connectivity. Cells. 2021;10(12):3296.

[70] Koffler J, Zhu W, Qu X, et al. Biomimetic 3D-printed scaffolds for spinal cord injury repair. Nat Med. 2019;25(2):263-269.

[71] Assinck P, Duncan GJ, Hilton BJ, Plemel JR, Tetzlaff W. Cell transplantation therapy for spinal cord injury. Nat Neurosci. 2017;20(5):637-647.

[72] Li Y, Huo S, Fang Y, et al. ROCK inhibitor Y27632 induced morphological shift and enhanced neurite outgrowth-promoting property of olfactory ensheathing cells via YAP-dependent up-regulation of L1-CAM. Front Cell Neurosci. 2018;12:489

[73] Kumamaru H, Lu P, Rosenzweig ES, Kadoya K, Tuszynski MH. Regenerating corticospinal axons innervate phenotypically appropriate neurons within neural stem cell grafts. Cell Rep. 2019;26(9):2329-2339.

[74] Miron VE, Boyd A, Zhao JW, et al. M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination. Nat Neurosci. 2013;16(9):1211-1218.

[75] Plemel JR, Keough MB, Duncan GJ, et al. Remyelination after spinal cord injury: is it a target for repair?Prog Neurobiol. 2014;117:54-72.

[76] He Z, Jin Y. Intrinsic control of axon regeneration. Neuron. 2016;90(3):437-451.

[77] Lv B, Zhang X, Yuan J, et al. Biomaterial-supported MSC transplantation enhances cell-cell communication for spinal cord injury. Stem Cell Res Ther. 2021;12(1):36.

[78] Yuan T, Shao Y, Zhou X, et al. Highly permeable DNA supramolecular hydrogel promotes neurogenesis and functional recovery after completely transected spinal cord injury. Adv Mater. 2021;33(35):e2102428.

[79] Fan C, Li X, Xiao Z, et al. A modified collagen scaffold facilitates endogenous neurogenesis for acute spinal cord injury repair. Acta Biomater. 2017;51:304-316.

[80] Liu Y, Yu H, Yu P, et al. Gelatin methacryloyl hydrogel scaffold loaded with activated Schwann cells attenuates apoptosis and promotes functional recovery following spinal cord injury. Exp Ther Med. 2023;25(4):144.

[81] Caron I, Rossi F, Papa S, et al. A new three dimensional biomimetic hydrogel to deliver factors secreted by human mesenchymal stem cells in spinal cord injury. Biomaterials. 2016;75:135-147.

[82] Wang K, Lin S, Nune KC, Misra RD. Chitosan-gelatin-based microgel for sustained drug delivery. J Biomater Sci Polym Ed. 2016;27(5):441-453.

[83] Olson HE, Rooney GE, Gross L, et al. Neural stem cell- and Schwann cell-loaded biodegradable polymer scaffolds support axonal regeneration in the transected spinal cord. Tissue Eng. 2009;15(7):1797-1805.

[84] Zeng X, Zeng YS, Ma YH, et al. Bone marrow mesenchymal stem cells in a three-dimensional gelatin sponge scaffold attenuate inflammation, promote angiogenesis, and reduce cavity formation in experimental spinal cord injury. Cell Transplant. 2011;20(11-12):1881-1899.

[85] Courtine G, Sofroniew MV. Spinal cord repair: advances in biology and technology. Nat Med. 2019;25(6):898-908.

[86] Liberson WT, Holmquest HJ, Scot D, Dow M. Functional electrotherapy: stimulation of the peroneal nerve synchronized with the swing phase of the gait of hemiplegic patients. Arch Phys Med Rehabil. 1961;42:101-105.

[87] Marquez-Chin C, Popovic MR. Functional electrical stimulation therapy for restoration of motor function after spinal cord injury and stroke: a review. Biomed Eng Online. 2020;19(1):34.

[88] Martin R, Sadowsky C, Obst K, Meyer B, McDonald J. Functional electrical stimulation in spinal cord injury:: from theory to practice. Top Spinal Cord Inj Rehabil. 2012;18(1):28-33.

[89] Karamian BA, Siegel N, Nourie B, et al. The role of electrical stimulation for rehabilitation and regeneration after spinal cord injury. J Orthop Traumatol. 2022;23(1):2.

[90] Graupe D, Kohn KH. Functional neuromuscular stimulator for short-distance ambulation by certain thoracic-level spinal-cord-injured paraplegics. Surg Neurol. 1998;50(3):202-207.

[91] Moineau B, Marquez-Chin C, Alizadeh-Meghrazi M, Popovic MR. Garments for functional electrical stimulation: design and proofs of concept. J Rehabil Assist Technol Eng. 2019;6:2055668319854340.

[92] Crowley ST, Fukushima Y, Uchida S, Kataoka K, Itaka K. Enhancement of motor function recovery after spinal cord injury in mice by delivery of brain-derived neurotrophic factor mRNA. Mol Ther Nucleic Acids. 2019;17:465-476.

[93] Keefe KM, Sheikh IS, Smith GM. Targeting neurotrophins to specific populations of neurons: NGF, BDNF, and NT-3 and their relevance for treatment of spinal cord injury. Int J Mol Sci. 2017;18(3):548

[94] Xu D, Wu D, Qin M, et al. Efficient delivery of nerve growth factors to the central nervous system for neural regeneration. Adv Mater. 2019;31(33):e1900727.

[95] Goldshmit Y, Frisca F, Pinto AR, et al. Fgf2 improves functional recovery-decreasing gliosis and increasing radial glia and neural progenitor cells after spinal cord injury. Brain Behav. 2014;4(2):187-200.

[96] Li G, Che MT, Zeng X, et al. Neurotrophin-3 released from implant of tissue-engineered fibroin scaffolds inhibits inflammation, enhances nerve fiber regeneration, and improves motor function in canine spinal cord injury. J Biomed Mater Res. 2018;106(8):2158-2170.

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