Baucher Guillaume, Liabeuf Sylvie, Brocard Cécile, Ponz Aurélie, Baumstarck Karine, Troude Lucas, Leone Marc, Roche Pierre-Hugues, Brocard Frédéric
Institut de Neurosciences de la Timone, Aix-Marseille Université, CNRS, Marseille, France.
AP-HM, Hôpital Universitaire Nord, Neurochirurgie adulte, Marseille, France.
PLoS One. 2025 May 21;20(5):e0319635. doi: 10.1371/journal.pone.0319635. eCollection 2025.
Spinal cord injury and traumatic brain injury are major causes of long-term disability and are often complicated by spasticity, a motor disorder characterized by increased muscle tone and exaggerated reflexes that significantly impair quality of life. Current diagnostic methods lack the sensitivity needed to accurately predict the severity of injury or the onset and progression of spasticity. Trauma-induced calcium dysregulation activates calpains, a family of proteases that cleave sodium channels, disrupting their inactivation and increasing persistent sodium currents. This cascade drives the overexcitability of motoneurons, contributing to the development of spasticity. Consequently, sodium channel fragments have emerged as promising biomarkers that link injury mechanisms to clinical outcomes. The present SpasT-SCI-T clinical trial protocol aims to evaluate sodium channel fragments as blood biomarkers for assessing the severity of spinal cord and traumatic brain injuries, as well as their potential to predict clinical outcomes, including the development of spasticity. This prospective, multicenter, case-control and cohort study involves 40 participants: 20 individuals with spinal cord injury, 10 individuals with traumatic brain injury, and 10 healthy controls. Blood samples are collected within six hours of injury and at follow-up points over six months. Clinical outcomes, including spasticity (assessed using the Modified Ashworth Scale), neurological recovery (measured by the American Spinal Injury Association Impairment Scale and Glasgow Coma Scale), and quality of life (evaluated using the Short Form-36 Health Survey), are analyzed in correlation with biomarker levels. We anticipate that calpain-mediated sodium channel fragments will transform the management of central nervous system injuries by enabling early diagnosis, improving prognostic accuracy, and guiding personalized therapeutic strategies. The clinical trial is registered on ClinicalTrials.gov (NCT06532760, January 10, 2024), with Assistance Publique-Hôpitaux de Marseille as the sponsor.
脊髓损伤和创伤性脑损伤是导致长期残疾的主要原因，并且常常伴有痉挛，这是一种运动障碍，其特征为肌张力增加和反射亢进，会显著损害生活质量。目前的诊断方法缺乏准确预测损伤严重程度或痉挛发作及进展所需的敏感性。创伤诱导的钙调节异常会激活钙蛋白酶，这是一类蛋白酶，可切割钠通道，破坏其失活并增加持续性钠电流。这一连锁反应会导致运动神经元过度兴奋，促使痉挛的发展。因此，钠通道片段已成为有前景的生物标志物，可将损伤机制与临床结果联系起来。目前的SpasT-SCI-T临床试验方案旨在评估钠通道片段作为血液生物标志物，用于评估脊髓损伤和创伤性脑损伤的严重程度，以及它们预测临床结果（包括痉挛发展）的潜力。这项前瞻性、多中心、病例对照和队列研究涉及40名参与者：20名脊髓损伤患者、10名创伤性脑损伤患者和10名健康对照者。在受伤后6小时内以及六个月的随访点采集血样。分析临床结果，包括痉挛（使用改良Ashworth量表评估）、神经恢复（通过美国脊髓损伤协会损伤量表和格拉斯哥昏迷量表测量）和生活质量（使用简短36健康调查评估）与生物标志物水平的相关性。我们预计，钙蛋白酶介导的钠通道片段将通过实现早期诊断、提高预后准确性和指导个性化治疗策略，改变中枢神经系统损伤的管理方式。该临床试验已在ClinicalTrials.gov上注册（NCT06532760，2024年1月10日），由马赛公立医院集团作为申办者。
