Supercharge End-to-Side Nerve Transfer: Systematic Review

Introduction

High ulnar nerve injuries have exceptionally poor outcomes,^1,2 particularly because motor end plates irreversibly degenerate before the regenerated ulnar nerve axons are able to reinnervate the intrinsic muscles of the hand. ³ To decrease the time to reinnervation of the intrinsic motor end plates, a supercharged end-to-side (SETS) anterior interosseous to ulnar motor nerve transfer has been proposed.^4-10

However, there is concern about a potential lack of basic science support of the nerve transfer’s mechanism. Specifically, questions have been raised about whether SETS axons reach the target muscle; how synchronous contracture occurs in the setting of multiple signals; and whether all fascicles of the deep motor branch of the median nerve become innervated with SETS? ¹¹ However, axon regeneration across a nerve coaptation has been demonstrated in an animal model. ¹² In addition, the same group found that in the setting of an incomplete nerve injury, a SETS transfer enhanced recovery and demonstrated increased muscle force. This work further exhibited how a nerve transfer with far fewer fibers could innervate a large nerve, as is the case with SETS. ¹³

Ultimately, the function of the SETS is to create a functional Martin Gruber ¹⁴ to “babysit” ¹⁵ intrinsic function in the hand^16,17 until proximal axons have the time to reach their distal neuromuscular junction. The data on SETS are comprised primarily of retrospective reports.^5-8 The purpose of this study is to review the demographics, outcomes, and complications following SETS for proximal ulnar nerve injuries.

Materials and Methods

The present study is reported following the PRISMA guidelines. ¹⁸ There was no source of funding or support for this analysis.

Results

The search resulted in 73 potentially eligible studies, while only 4 met inclusion and exclusion criteria (Figure 1). Three studies were retrospective case series,^5,6,8 while one was a retrospective comparative cohort. ⁷ In total, 78 patients underwent SETS and were included. Most patients (33.3%) underwent SETS for an ulnar nerve lesion in continuity, the average age was 46.5 years, and the average follow-up was 10 months. The average duration of symptoms before surgery was 99 weeks, all patients had weakness and numbness, nearly all (96%) had atrophy, and half (53%) had pain (Table 1).

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Figure 1.

Flow diagram depicting study selection algorithm (created using PRISMA 2009 Flow diagram, version 2.1.3).

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Table 1:

Demographics, pre-operative exam, and surgical variables.

Study	Points	Follow up, mo	Age, y	Male	Condition	Symptom duration	Location of injury	pWeakness	pNumbness	pPain	p2pt >6mm	pAtrophy	pPositive Froment’s sign
Haase et al, 2002 6	2	11.5	46.5	2	2 transection	3.5wk	1 Elbow 1 Upper Arm	1	NR	NR	NR	NR	NR
Baltzer et al, 2016 7	13	13.5	35	NR	7 transection 6 LIC	16wk	7 Elbow 5 Proximal forearm 1 Upper arm	13	NR	NR	NR	13	NR
Novak et al, 2002 5	8	18	38	5	8 PUNI	12wk	8 Proximal to elbow	NR	NR	NR	NR	NR	NR
Davidge et al, 2015 8	55	8	50.5	38	23 compression 20 LIC 5 transection 6 motor neuropathy 1 neuritis	134wk	20 Elbow 13 Brachial Plexus 6 Diffuse neuropathy 5 Proximal forearm 4 Cervical spine 4 Multilevel 3 Upper Arm	55	55	29	36	52	45
Total or Weighted Average	78	10	46.5	45 (69%)	33.3% LIC 29.5%Compression 17.9% Transection 10.3% PUNI	98.8 wk 24.7 mo	28 (35.9%) Elbow	69 (100%)	55 (100%)	29 (53%)	36 (65%)	65 (96%)	45 (82%)

LIC: lesion in continuity; wk: weeks; mo: months; NR: not recorded; UN: ulnar nerve; PUNI: proximal ulnar nerve injury; p: preoperative; 2pt: two point.

The concomitant procedures included Guyon canal release (64), flexor digitorum profundus (37), carpal tunnel release (28), ulnar nerve transposition (27), posterior interosseous nerve decompression (5), pronator release (4), tenolysis (4), adductorplasty (2), sensory nerve transfer (2), other nerve graft (2), median to radial nerve transfer (2), radial nerve tendon transfers (2), medial antebrachial cutaneous nerve transposition (2), brachial plexus tumor excision (1), and free flap for elbow coverage (1).

Postoperatively, the grip and key pinch strength improved 202% and 179%, respectively, from the preoperative assessment. The vast majority (91.9%) recovered intrinsic function at an average of 3.7 months (Table 2). In addition, the average preoperative first dorsal interossei strength Medical Research Council (MRC) was 1.3 preoperatively and 3.0 postoperatively. While 27 of 39 patients regained function between 3 and 12 months, 9 had rapid recovery (between 1 and 3 months).

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Table 2.

Postoperative Outcomes.

First author, year	Grip %cf UAS	Grip improvementcf pre-op IP	Key %cf UAS	Key improvementcf pre-op IP	Opp %cf UAS	Total N intrinsic recovery	Time to intrinsic recovery
Haase, 2002	NR	NR	NR	NR	NR	2/2	9 mo
Baltzer, 2016	62	NR	52	NR	45	11/13	2.9 mo
Novak, 2002	NR	695%	NR	630%	NR	8/8	NR
Davidge, 2015	NR	130%	NR	130%	NR	36/39	Reported otherwise
Total	62	202%	52	179%	45	57/62 (91.9%)	3.7 mo

Note. grip = grip strength; cf UAS = compared to the unaffected side; cf pre-op IP = compared to preoperative ipsilateral side; key = key pinch strength; opp = opposition; NR = not recorded.

Eight percent of patients did not recover intrinsic strength. No complications were reported in any of the 78 patients.

Discussion

The purpose of this analysis is to amass the reported cases of SETS and evaluate the indications, outcomes, and complications. The 2 key findings of this analysis were, first, SETS yielded a high return of intrinsic function (91.9%) at 3.7 months. Second, while 8% did not recover intrinsic strength, no other complications were noted in any of the 4 studies. This analysis demonstrates that SETS is a successful procedure with limited morbidity, which may restore intrinsic function in patients with proximal nerve injuries.

While most studies incorporated in the present analysis were retrospective case series,^5,6,8 one retrospective comparative study was included. ⁷ Thirteen proximal ulnar nerve injuries treated with repair and SETS were compared to 13 with repair alone. Only 38% of the latter cohort, compared with 84% of the SETS patients, regained intrinsic recovery of the hand. After nerve transection, intrinsic recovery favored SETS (85% vs 14%). However, after a compressive injury, there was no difference between SETS and repair alone (67% vs 67%). Although there was no power to compare transection with compressive injuries, the authors hypothesized that the discrepancy between transection and compression in SETS may be associated with the inflammatory phase, which follows a transection injury and may enhance peripheral nerve regeneration.

For most patients, the timing of the return of intrinsic function was gradual but generally within 12 months of SETS with an average of 3.7 months. ⁸ However, in the largest of the series, 16% of patients had recovery within 3 months, even including several who had sustained a compressive injury. ⁷ Conversely, a minority of patients in the present analysis (8%) did not recover intrinsic function. In the patients who did not recover intrinsic strength, there was a correlation with peripheral neuropathy, prior anterior interosseous nerve injury, and absent ulnar nerve preoperative compound muscle action potentials (CMAPs). A lack of CMAPs demonstrates a muscle’s inability to be reinnervated after prolonged denervation. ⁸ In addition, age, sex, comorbid medical condition, or proximity of the ulnar nerve injury did not affect recovery of intrinsic muscle recovery. ⁸ These findings underscore the importance of SETS: to reinnervate the intrinsic as quickly as possible.

Besides the 8% of patients who did not recover intrinsic function, there were no other reported complications. In addition, in the largest analysis which recorded pronation strength, there was no pronation weakness postoperatively. ⁸ The limited morbidity may lower the surgeon’s threshold to offer the procedure to patients with a high ulnar nerve injury. While it is possible that complications are under reported in the 4 papers included in the present analysis, future investigations should carefully monitor for complications postoperatively.

Another limitation of this systematic review is the limited power. A large multicenter prospective study with standardized preoperative and postoperative assessments, to include electrodiagnostic studies and a closer analysis of complications, would be necessary to effectively understand the efficacy of SETS. In addition, the study’s external validity is limited by the retrospective nature of the study with varying patient populations and concomitant procedures (particularly ulnar nerve release) as well by the fact that most patients are from a single study group. Despite the study’s limitations, the present analysis is the largest review of SETS indications, outcomes, and complications. The SETS is an effective treatment safe and successful procedure, which may restore intrinsic function in patients with proximal nerve injuries.