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使用神经缝合术和包括聚乙二醇在内的生物工程解决方案对离断的指神经进行快速有效的融合修复:一例报告

Rapid and effective fusion repair of severed digital nerves using neurorrhaphy and bioengineered solutions including polyethylene glycol: A case report.

作者信息

Lopez Stephen, Bittner George D, Treviño Richard C

机构信息

Canton Plastic Surgery, Canton, OH, United States.

Department of Neuroscience, University of Texas at Austin, Austin, TX, United States.

出版信息

Front Cell Neurosci. 2023 Jan 19;16:1087961. doi: 10.3389/fncel.2022.1087961. eCollection 2022.

Abstract

Peripheral nerve injuries (PNIs) that consist of simple nerve severance often result in severe motor impairment and permanent loss of function. Such patients face significant costs and pose major burdens to healthcare systems. Currently, the most promising surgical technique to achieve the best clinical outcome after such PNIs is immediate primary coaptation of severed nerve ends by microsutures (neurorrhaphy). However, recovery is often poor and delayed for many months due to Wallerian degeneration (WD) and slow (1-2 mm/day) axonal outgrowths from severed proximal axons that may not properly reinnervate denervated afferent/efferent targets that have atrophied. In contrast, recent pre-clinical studies using polyethylene glycol (PEG) to facilitate primary nerve repair have greatly improved the rate and extent of sensory and motor recovery and prevented much WD and muscle atrophy. That is, PEG-fused axons rapidly establish proximal-distal axoplasmic/axolemmal continuity, which do not undergo WD and maintain the structure and function of neuromuscular junction (NMJ). PEG-fused axons rapidly reinnervate denervated NMJs, thereby preventing muscle atrophy associated with monthslong denervation due to slowly regenerating axonal outgrowths. We now describe PEG-mediated fusion repair of a digital nerve in each of two patients presenting with a digital laceration resulting in total loss of sensation. The first patient's tactile perception improved markedly at 3 days postoperatively (PO). Two-point discrimination improved from greater than 10 mm at initial presentation to 4 mm at 11-week PO, and the Semmes-Weinstein monofilament score improved from greater than 6.65 to 2.83 mm, a near-normal level. The second patient had severe PO edema and scar development requiring a hand compression glove and scar massage, which began improving at 11-week PO. The sensory function then improved for 4 months PO, with both two-point discrimination and Semmes-Weinstein scores approaching near-normal levels at the final follow-up. These case study data are consistent with data from animal models. All these data suggest that PEG-fusion technologies could produce a paradigm shift from the current clinical practice of waiting days to months to repair ablation PNIs with autografts, anucleated nerve allografts, or conduits in which the patient outcome is solely dependent upon axon regeneration over months or years.

摘要

由单纯神经切断构成的周围神经损伤(PNIs)常常导致严重的运动功能障碍和永久性功能丧失。这类患者面临高昂费用,给医疗系统带来重大负担。目前,在此类周围神经损伤后实现最佳临床结果最有前景的外科技术是通过显微缝合(神经缝合术)立即对切断的神经末端进行一期端端吻合。然而,由于华勒氏变性(WD)以及切断的近端轴突缓慢的(每天1 - 2毫米)轴突生长,恢复通常较差且延迟数月,这些轴突可能无法正确地重新支配已经萎缩的失神经传入/传出靶点。相比之下,最近使用聚乙二醇(PEG)促进一期神经修复的临床前研究极大地提高了感觉和运动恢复的速度和程度,并预防了大量的华勒氏变性和肌肉萎缩。也就是说,PEG融合的轴突迅速建立近端到远端的轴浆/轴膜连续性,不会发生华勒氏变性,并维持神经肌肉接头(NMJ)的结构和功能。PEG融合的轴突迅速重新支配失神经的神经肌肉接头,从而预防因缓慢再生的轴突生长导致的长达数月的失神经相关的肌肉萎缩。我们现在描述了两例因手指撕裂伤导致感觉完全丧失的患者,对其指神经进行PEG介导的融合修复的情况。第一位患者术后3天触觉感知明显改善。两点辨别觉从最初就诊时大于10毫米改善到术后11周时的4毫米,Semmes - Weinstein单丝评分从大于6.65改善到2.83毫米,接近正常水平。第二位患者术后水肿严重且有瘢痕形成,需要使用手部加压手套并进行瘢痕按摩,在术后11周开始改善。然后感觉功能在术后4个月持续改善,在最后一次随访时两点辨别觉和Semmes - Weinstein评分均接近正常水平。这些病例研究数据与动物模型的数据一致。所有这些数据表明,PEG融合技术可能会引发一场范式转变,从目前等待数天至数月用自体移植物、去细胞神经同种异体移植物或导管修复切断性周围神经损伤的临床实践中转变出来,在当前实践中患者的预后完全依赖于数月或数年的轴突再生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1def/9892895/a86d5fbd2590/fncel-16-1087961-g001.jpg

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