End-to-Side Nerve Repair: Review of the Literature and Clinical Indications Linda T. Dvali, MD a, * , Terence M. Myckatyn, MD b a Division of Plastic and Reconstructive Surgery, University of Toronto, University Health Network, Toronto Western Division, 2-400, 399 Bathurst Street, Toronto, Ontario, M5T 2S8, Canada b Division of Plastic and Reconstructive Surgery, Washington University School of Medicine, Suite 17424 East Pavilion, One Barnes Jewish Hospital Plaza, St. Louis, MO 63110, USA End-to-side (ETS) nerve repair involves coapt- ing the distal stump of a transected nerve to the side of a donor nerve. Attachment to the donor nerve may occur either without alteration of the donor nerve or in conjunction with the creation of some form of injury (deliberate or nondeliberate) to the donor nerve. This technique was described over a century ago as a reconstructive strategy for facial nerve injury and brachial plexus avulsion injuries [1–3]. However, the technique never gained wide popularity. The introduction of the microscope and improving microscopic tech- niques revolutionized the methods of primary repair and interpositional nerve grafting and likely explain why ETS techniques were not ini- tially adapted [4,5]. The ETS technique was revived in the early 1990s when Viterbo and col- leagues [6–8] demonstrated histologic and electro- physiologic evidence of reinnervation into the distal stump in a rat model. The benefits of reviv- ing the ETS technique seem obvious given its use where traditional nerve repair and grafting are un- available or likely to result in poor functional out- comes. For example, it can be used in injuries where the proximal stump of an injured nerve is unavailable or distant to its end target, or in the case of a long nerve gap. Additionally donor site morbidity associated with nerve graft harvest can be avoided. This article evaluates recent stud- ies on ETS repair, focusing on evidence for collat- eral sprouting, the role of the epineurial or perineurial windows in ETS repairs, sensory versus motor regeneration after ETS repair, and recommendations regarding the current clinical applications for ETS techniques. The exact cellular processes that occur in the donor nerve after ETS nerve repair are the sub- jects of continued controversy. The main area of controversy concerns the proposed source of regenerating axons into the distal nerve following ETS repair. In general, there are three possibili- ties: (1) invasion from the transected proximal stump of the injured nerve, (2) regeneration from donor nerve axons that were damaged during nerve preparation, or (3) regeneration from true ‘‘collateral sprouting’’ from the ETS site. The term ‘‘collateral sprouting’’ implies spon- taneous, de novo sprouting of nerve axons in the absence of nerve injury. The concept of axonal sprouting in the absence of injury is controversial but, in mylenated nerves, it is thought to arise from the nodes of Ranvier just proximal to the level of the coaptation. ‘‘Regenerative sprouting,’’ in contrast, occurs in response to nerve injury and, according to widely accepted opinions, in both ETS and end-to-end models of nerve reconstruc- tion. For the purposes of this article, we will specifically refer to ‘‘spontaneous collateral sprouting’’ if no nerve injury is implied, and ‘‘regenerative sprouting’’ when axonal disruption is suspected. Spontaneous collateral sprouting, without any evidence of nerve injury, is yet to be conclusively proven in the literature. The presence of axons within a recipient nerve after ETS repair is often presented as supporting evidence for collateral sprouting. While these axons may represent true collateral sprouting, they may also be false-positive results. Other * Corresponding author. E-mail address: linda.dvali@uhn.on.ca (L.T. Dvali). 0749-0712/08/$ - see front matter Ó 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.hcl.2008.04.006 hand.theclinics.com Hand Clin 24 (2008) 455–460