Hawryluk Gregory W J, Rowland James, Kwon Brian K, Fehlings Michael G
Division of Genetics and Development, Toronto Western Research Institute, Toronto, Ontario, Canada.
Neurosurg Focus. 2008;25(5):E14. doi: 10.3171/FOC.2008.25.11.E14.
Over the past 2 decades, advances in understanding the pathophysiology of spinal cord injury (SCI) have stimulated the recent emergence of several therapeutic strategies that are being examined in Phase I/II clinical trials. Ten randomized controlled trials examining methylprednisolone sodium succinate, tirilizad mesylate, monosialotetrahexosylganglioside, thyrotropin releasing hormone, gacyclidine, naloxone, and nimodipine have been completed. Although the primary outcomes in these trials were laregely negative, a secondary analysis of the North American Spinal Cord Injury Study II demonstrated that when administered within 8 hours of injury, methylprednisolone sodium succinate was associated with modest clinical benefits, which need to be weighed against potential complications. Thyrotropin releasing hormone (Phase II trial) and monosialotetrahexosylganglioside (Phase II and III trials) also showed some promise, but we are unaware of plans for future trials with these agents. These studies have, however, yielded many insights into the conduct of clinical trials for SCI. Several current or planned clinical trials are exploring interventions such as early surgical decompression (Surgical Treatment of Acute Spinal Cord Injury Study) and electrical field stimulation, neuroprotective strategies such as riluzole and minocycline, the inactivation of myelin inhibition by blocking Nogo and Rho, and the transplantation of various cellular substrates into the injured cord. Unfortunately, some experimental and poorly characterized SCI therapies are being offered outside a formal investigational structure, which will yield findings of limited scientific value and risk harm to patients with SCI who are understandably desperate for any intervention that might improve their function. Taken together, recent advances suggest that optimism for patients and clinicians alike is justified, as there is real hope that several safe and effective therapies for SCI may become available over the next decade.
在过去20年里，对脊髓损伤（SCI）病理生理学认识的进展激发了近期几种治疗策略的出现，这些策略正在进行I/II期临床试验研究。十项关于琥珀酸甲泼尼龙、甲磺替拉扎特、单唾液酸四己糖神经节苷脂、促甲状腺激素释放激素、加环利定、纳洛酮和尼莫地平的随机对照试验已经完成。尽管这些试验的主要结果大多为阴性，但对北美脊髓损伤研究II的二次分析表明，在损伤后8小时内给予琥珀酸甲泼尼龙可带来一定的临床益处，不过这需要与潜在并发症相权衡。促甲状腺激素释放激素（II期试验）和单唾液酸四己糖神经节苷脂（II期和III期试验）也显示出一些希望，但我们并不清楚这些药物未来的试验计划。然而，这些研究为SCI的临床试验实施提供了许多见解。目前正在进行或计划进行的几项临床试验正在探索诸如早期手术减压（急性脊髓损伤的外科治疗研究）和电场刺激等干预措施，诸如利鲁唑和米诺环素等神经保护策略，通过阻断Nogo和Rho使髓磷脂抑制失活，以及将各种细胞基质移植到受损脊髓中。不幸的是，一些未经充分实验和特征描述的SCI治疗方法正在正规研究结构之外提供，这将产生科学价值有限的结果，并可能对那些渴望任何可能改善其功能的干预措施的SCI患者造成伤害。总体而言，近期的进展表明，患者和临床医生都有理由感到乐观，因为在未来十年里，确实有可能出现几种安全有效的SCI治疗方法。
