Tos Pierluigi, Artiaco Stefano, Papalia Igor, Marcoccio Ignazio, Geuna Stefano, Battiston Bruno
Reconstructive Microsurgery Unit, Department of Orthopedics, C.T.O. Hospital, Turin 10126, Italy.
Int Rev Neurobiol. 2009;87:281-94. doi: 10.1016/S0074-7742(09)87014-1.
Translation of laboratory results to the patient is a critical step in biomedical research and sometimes promising basic science and preclinical results fail to meet the expectations when translated to the clinics. End-to-side (ETS) nerve regeneration is an example of an innovative neurobiological concept, which, after having generated great expectations in experimental and preclinical studies, provided very conflicting results when applied to clinical case series. A number of basic science studies have shown that ETS neurorrhaphy, in fact, is able to induce collateral sprouting from donor nerve's axons, allowing for massive repopulation of the distal nerve stump. Experimental studies have also shown that ETS neurorrhaphy can recover voluntary control of skeletal muscles and that voluntary motor function recovery can be achieved both with agonistic and antagonistic donor nerves, thus widening the potential clinical indications. However, clinical case series reported so far, did not meet these promises and results have been rather conflicting, especially regarding repair of proximally located mixed nerves. In contrast, ETS reconstruction of distal sensory nerve lesions led to a more positive outcome and, most importantly, consistent results among international centers carrying out clinical trials. Concluding, ETS is a promising microsurgical approach for nerve coaptation, based on a convincing and innovative neurobiological concept. However, conflicting clinical results and disagreement among surgeons regarding its employment suggest that this technique should still be considered an ultima ratio, reserved for cases where no other repair technique can be attempted. New data coming from neurobiological research will help further enlarge the clinical indications of ETS nerve reconstruction, explain the different results found in laboratory animals and humans, and contribute to new treatments and rehabilitation strategies aimed at improving the efficacy of nerve regeneration after ETS neurorrhaphy.
向患者解读实验室检查结果是生物医学研究中的关键一步，有时很有前景的基础科学和临床前研究结果在转化到临床时却未能达到预期。端侧（ETS）神经再生就是一个创新性神经生物学概念的例子，它在实验和临床前研究中引发了极大期望，但应用于临床病例系列时却得出了非常矛盾的结果。许多基础科学研究表明，事实上，ETS神经缝合能够诱导供体神经轴突的侧支发芽，使远端神经残端大量重新植入。实验研究还表明，ETS神经缝合能够恢复骨骼肌的自主控制，并且使用激动性和拮抗性供体神经都能实现自主运动功能恢复，从而拓宽了潜在的临床适应症。然而，迄今为止报道的临床病例系列并未实现这些预期，结果相当矛盾，尤其是在近端混合神经的修复方面。相比之下，ETS修复远端感觉神经损伤取得了更积极的结果，最重要的是，开展临床试验的国际中心之间的结果一致。总之，基于令人信服的创新性神经生物学概念，ETS是一种有前景的神经吻合显微外科方法。然而，临床结果相互矛盾以及外科医生在其应用上存在分歧，这表明该技术仍应被视为最后的手段，仅用于无法尝试其他修复技术的病例。神经生物学研究的新数据将有助于进一步扩大ETS神经重建的临床适应症，解释在实验动物和人类中发现的不同结果，并为旨在提高ETS神经缝合后神经再生疗效的新治疗方法和康复策略做出贡献。
