Modified Partial Radial to Axillary Nerve Transfer as the Index Procedure for Isolated Axillary Nerve Injury

Abstract

Objective:

Axillary nerve injuries often produce profound functional deficits. Beyond expectant management or microsurgical repair, treatment is generally limited to salvage procedures. We present the results of partial radial-to-axillary nerve transfer as the index procedure for treatment of axillary nerve injury after failure of initial conservative management.

Methods:

Minimum 2-year follow-up data was collected and retrospectively analyzed for this single-surgeon cohort of patients with isolated axillary nerve injury. The injury was confirmed with electromyography (EMG), and all patients underwent a nerve transfer as the index intervention. All patients were evaluated for donor-site neuromuscular morbidity, and deltoid muscle biopsies were obtained intra-operatively from 8 patients for motor endplate (MEP) morphometric analysis. Age at time of surgery ranged from 22–68 years, and time from injury to surgery ranged from 2–120 months. Shoulder range of motion (ROM) and Medical Research Council (MRC) muscle strength scores were recorded pre-op and post-op.

Results:

There were 16 patients in the final sample (median age 56, 15 males, 1 female, 93.75% White, 6.25% Black). Significant improvements in pre-op versus final post-op function were observed: average MRC score improved by 2.82± 1.33 (p<0.01), while average active forward-flexion improved by 108.18 ± 44.17° (p < 0.01), abduction by 94.91 ± 41.58° (p < 0.01), and external rotation by 36.67 ± 27.04° (p < 0.01). Surviving MEPs were observed in biopsies of denervated muscles from all patients, even those greater than 6 months from injury.

Interpretation:

In patients with an isolated axillary nerve injury, when an appropriate donor radial nerve branch can be identified, partial radial-to-axillary nerve transfer as the index treatment procedure offers the possibility of significantly improving shoulder motion and functional strength, without detectable donor-site morbidity. Furthermore, the opportunity for meaningful functional improvement was observed even in patients treated with surgery beyond 6 months from the time of nerve injury and correlated with the observed persistence of deltoid MEPs at later time points.

Level of Evidence:

Level IV, Case Series, Treatment Study

Introduction:

Peripheral nerve injuries (PNIs), such as axillary nerve injuries, often create significant morbidity. They occur in approximately 5% of trauma patients in the U.S., and are predominantly in the upper extremities of males in their fourth decade of life.^22,28,35 These injuries, whether caused by traumatic or iatrogenic events, often severely impair function as regeneration is limited secondary to the distance required for motor axons to reinnervate muscles with ensuing motor atrophy secondary to prolonged denervation.^{12,19,21,22,34}

The deltoid muscle, innervated by the axillary nerve, is critical for arm elevation, generating over 50% of the force to elevate the arm in the scapular plane.³⁸ It dynamically stabilizes the shoulder, particularly when the arm is externally rotated and abducted.¹⁹ Consequently, any damage to the deltoid muscle usually leads to significant, long-lasting functional deficits and disability in daily activities, highlighting the devastating impact of axillary nerve injuries.^12,19,21 Initial management of nerve injuries, including isolated axillary nerve injuries, is often expectant, as many clinicians—particularly those who do not routinely manage peripheral nerve injuries—initially observe for spontaneous recovery because the injury may represent a neuropraxic stretch injury (Sunderland grade I).³³ Moreover, outcomes following an axillary nerve repair (with or without a graft) can vary significantly depending on factors such as patient age, injury severity, timing of intervention, and extent of denervation. Unfortunately, functional outcomes following repair generally remain disappointing, with review analyses demonstrating less than 30% of patients recovering greater than 2/5 deltoid strength per Medical Research Council (MRC) scoring.⁴⁰ Delayed surgical interventions are even less effective if performed after 6 months, as terminal motor endplate (MEP) degeneration occurs secondary to the absence of neural input.²⁶ When the deltoid remains denervated for prolonged periods, it is believed that few, if any MEPs remain, creating an environment where the denervated muscle is no longer receptive to reinnervation. For these patients, few options remain besides salvage procedures such as shoulder arthrodesis or pedicled pectoralis major tendon transfer.^10,20,29,40 These procedures carry significant morbidity and leave patients with minimal functional motion, particularly in overhead activities.^6,11,15,33 Consequently, nerve transfers for isolated axillary nerve injuries are appealing because they involve donor nerves closer to target muscles and may potentially improve functional reinnervation. However, their success may also be limited if too much time passes from injury to intervention, as MEPs in denervated muscles may completely degenerate.^6,14,30 Prior studies frequently combine isolated axillary nerve injuries with broader brachial plexus reconstruction cohorts, which limits the characterization of clinically meaningful shoulder recovery in isolated injuries.^{9, 23, 37} In addition, limited data exists regarding the persistence and morphology of MEPs in chronically denervated deltoid muscle following axillary nerve injury. The radial nerve is an ideal donor nerve because: (1) the triceps action is synergistic with shoulder abduction, (2) the radial nerve typically has redundant branches that allow for transfer with limited-to-no functional deficits, and (3) anatomic proximity to the deltoid.^2,30 While partial radial-to axillary nerve transfers are frequently utilized concomitantly with the reconstruction of other PNIs such as brachial plexus injuries, this procedure can be performed for isolated axillary nerve injury.^21,25 Here we present outcomes of partial radial-to-axillary nerve transfer performed as the index procedure for treatment of isolated axillary nerve injury.

Materials and Methods:

Inclusion Criteria:

Patients undergoing elective partial radial-to-axillary nerve transfer surgery for isolated axillary nerve injury from a single surgeon between 2014–2022 were enrolled under a university IRB-approved protocol, and informed patient consent was obtained for muscle biopsies.

Patient characteristics (Table 1):

Table 1:

Summary Table with Patient Data and EMG Findings

							Pre-Nerve Transfer ROM (°)			Post-Nerve Transfer ROM (°)			EMG Findings
Study ID	Age	Gender (M=0, F=1)	Race	MOI	Time from Injury to Surgery (Months)	End-to-end (A) or end-to-side (B)	Forward Flexion	Abduction	External Rotation	Forward Flexion	Abduction	External Rotation	Fibrillations	Nascent Potentials	Motor unit recruitment	Motor unit potential
1	67	1	White	Iatrogenic s/p RC repair	12	A	20	80	30	90	90	35	2+	Many	reduced, rapid rate	long duration, high amp
2	62	0	White	Iatrogenic	120	B	35	35	0	180	160	60	2+	Many	reduced, rapid rate	long duration, high amp
3	58	0	White	Motorcycle Accident	4	B	45	45	60	180	170	70	NR	NR	reduced	NR
4	61	0	White	Acute anterior shoulder dislocation	4	B	50	50	10	160	150	45	1+, 2+	Many	reduced	long duration, high amp
5	53	0	Black	Stab Wound	7	A	35	36	0	140	110	60	3+	None	reduced	none
6	27	0	White	Motorcycle Accident	5	A	30	15	10	125	85	60	2+, 3+	None	reduced	none
7	56	0	White	Fall	26	Could not isolate fascicle, thus aborted	45	45	0	45	45	0	3+	None	reduced, normal rate	giant amp, normal duration
8	61	0	White	Fall	3	B	30	30	0	90	90	15	2+	Many	reduced, rapid rate	normal amp, long duration
9	34	0	White	Chronic posterior shoulder dislocation	3	A	35	35	0	160	140	60	1+, 2+	None	reduced, rapid rate	normal amp, duration
10	22	0	White	Motorcycle Accident	73	A	35	35	0	170	150	45	1+	None	single unit recruiment	long duration, high amp
11	52	0	White	Iatrogenic	7.5	B	35	35	0	180	160	60	2+	Few	reduced, rapid rate	long duration, high amp
12	42	0	White	Speedboat accident	5	B	30	30	0	45	30	10	2+	Many	reduced, rapid rate	normal amp, long duration
13	55	0	White	Iatrogenic	7	A	110	90	60	110	90	60	2+	None	NR	NR
14	61	0	White	Fall	6	B	30	20	NR	120	95	NR	N/R	None	reduced amplitude	none
15	57	0	White	Fall	4	B	30	30	NR	90	90	NR	N/R	None	< 5 MUs (reduced)	NR
16	68	0	White	Shoulder Dislocaton	2	B	40	50	NR	170	170	NR	NR	NR	NR	none

Average age at the time of surgery was 52.3 (range 22–68 years). The mean time from injury to surgery was 18.0 months (range 2–120). Self-reported patient sex and race data were collected from our institution’s EMR system. Ethnicity data were not consistently available and, therefore, could not be reliably collected. All but one patient underwent successful isolated nerve transfer; a redundant radial nerve branch could not be isolated, so no transfer was performed. Six patients underwent end-to-end nerve transfer, whereas nine underwent end-to-side transfer. End-to-side coaptation was preferentially performed in patients who demonstrated any deltoid muscle contraction with intraoperative nerve stimulation, indicating preserved proximal axillary nerve continuity and allowing augmentation of reinnervation while preserving the native axillary nerve. All patients were assessed pre-operatively with electromyography (EMG) by a fellowship-trained neurologist to characterize axillary nerve injury and assessed for the presence of fibrillation potentials, positive sharp waves, and nascent potentials.

Functional assessments:

Shoulder range of motion (ROM) and Medical Research Council (MRC) muscle strength scores (deltoid, triceps, wrist, and digit extension) were evaluated and recorded for all patients at pre-op and at final follow-up. Donor nerve-muscle morbidity was evaluated for all patients immediately postoperatively and at all follow-up visits. Statistical analyses of these functional measures were performed using the Student t-test with alpha set at 0.05. Patients were additionally stratified into 2 groups based on time from injury to surgery, ≤6 months and >6 months, to descriptively evaluate the relationship between surgical timing and postoperative functional recovery. Subgroup analysis by sex/gender was not performed due to the marked imbalance in representation (15 males, 1 female)

Surgical Technique:

Intraoperatively, long-acting paralytics and local anesthetics were NOT administered, so that intraoperative neural function could be accurately assessed. In all cases, an intraoperative nerve stimulator was used to identify an appropriate donor radial nerve branch. Nerve transfer was only performed when intraoperative stimulation confirmed the presence of a functionally redundant radial nerve branch that could be harvested while preserving critical upper extremity functions, including elbow, wrist, and finger extension. This assessment was performed within the early intraoperative period (within 60 minutes of induction) to optimize the reliability of neural stimulation and functional assessment. In one patient, a sufficiently redundant donor fascicle could not be safely isolated intraoperatively (each identifiable nerve branch produced a critical distal radial nerve motor function), and the transfer was therefore aborted to avoid potential donor morbidity.

For all patients, the recipient nerve was super-maximally stimulated intraoperatively with the nerve stimulator to evaluate extent of nerve injury. If there was no muscle contraction, an end-to-end transfer was performed. If there was evidence of muscle contraction (indicating some axillary nerve fiber continuity), an end-to-side transfer was performed in which a perineural window was created in the recipient nerve for anastomosis with the donor nerve. The modified partial radial-to-axillary nerve procedure was performed per previously described technique (Figure 1).^16,17

Figure 1:

Posterior view of radial to axillary nerve transfer. A. Relevant surgical anatomy of the radial and axillary nerve. B. Isolation of the motor radial nerve branch to the long head of triceps (marked by the white arrow) and neurolysis of the anterior branch of the axillary nerve (marked by the white X) C. Demonstrates coaptation of the donor radial nerve branch to the recipient axillary nerve.

Muscle biopsy harvest:

Deltoid muscle biopsies were collected from patients between 2015 and 2022 and were harvested from denervated muscles intraoperatively through the same surgical incision used for the nerve transfer. From the 16 cohort patients, 8 muscle biopsies were obtained from deltoid muscles—1 female and 7 males. Muscle biopsies were taken from the periphery of the muscle, in the middle of the leading edge of the deltoid as directly visualized immediately adjacent to where surgical retractors were placed. This location of harvest ensured both consistency in muscle sampling and minimal patient morbidity. After biopsy, each muscle sample was placed in a sterile container and transported on dry ice directly from the operating room to laboratory for processing. All biopsies were processed the same day as harvest.

Immunofluorescence analysis of MEPS and Tissue Imaging:

Tissue samples were stained with neurofilament (NF), synaptophysin (SYN), and acetylcholine receptor-α (AChR-α) antibodies.²⁷ NF and SYN are markers for axons and the presynaptic nerve terminal, respectively. AChR-α is one of the key subunits of postsynaptic motor endplates. Samples collected were imaged either via two-photon excitation microscopy as described by Gupta et al.,¹⁶ or Keyence BZ-X810 inverted fluorescence phase contrast microscope (for improved clarity). Image stacks of MEPs were analyzed for morphometrics. MEP morphology was quantified using BZ-X10 analyzer and ImageJ to assess the number of perforations, MEP area, and overall shape. MEP form was classified by two independent investigators as “normal pretzel, intermediate, or simple plaque” according to criteria described by Chao et al.⁴ In 2020, an optimization in the tissue clearing method was implemented, which allowed for a more precise and detailed assessment of MEP morphology. Therefore, the analysis presented here primarily focuses on the samples collected post-2020 to leverage the enhanced clarity provided by the updated method.

Postoperative follow-up:

From 16 treated patients, 11 had at least 2-year follow-up; mean follow-up in the studied cohort was 59.1 months (range, 24–118). Notably, one patient was lost to follow-up after two weeks. All patients were intended to be followed up for a minimum of two years to comprehensively evaluate procedure outcomes. Despite numerous attempts, we were unable to maintain contact with some patients to evaluate them at the two-year follow-up. Contrary to most patients who are lost to follow-up, these four patients actually had recovered function and were unwilling to return secondary to the distance required. All patients underwent donor nerve-muscle strength testing at all follow-up visits. No patient demonstrated any evidence of donor-site deficiency; all patients exhibited normal (M5) strength of triceps, wrist, and digit extension. No patient required revision surgery.

Electromyography:

All patients preoperatively displayed cardinal signs of muscle denervation per EMG (Table 1): 3 patients had 3+ fibrillation potentials, 8 had 2+ fibrillation potentials, and 1 had 1 fibrillation potentials. 12 patients were reported with significant reductions in motor unit recruitment, 1 patient had <5 motor unit recruitment, and 1 had single unit recruitment. Regarding motor unit potentials (MUPs): 5 patients had long-duration, high-amplitude MUPs, 4 had zero MUPs, 2 had long duration with normal amplitude, and 1 had high-amplitude with normal duration. Five patients had many nascent potentials, suggesting some early-stage reinnervation, while 8 patients had no detectable nascent potentials.

Functional outcomes assessment:

Mean preoperative deltoid MRC score was 1.55. This improved to a postoperative mean MRC score of 4.36, yielding a statistically significant average improvement of 2.82 ± 1.33 (p<0.01) (Table 2). Significant improvements from pre- to postoperative active ROM were observed (Figure 2), including an average forward-flexion increase of 108.18 ± 44.17° (p < 0.01), abduction improvement of 94.91 ± 41.58° (p < 0.01), and external rotation improvement of 36.67 ± 27.04° (p < 0.01) (Table 2). Active ROM data was also stratified by transfer type: end-to-end (Group A) and end-to-side (Group B). There was no significant difference between the groups (Table 3), though Group B tended to exhibit a greater average increase in shoulder forward-flexion and abduction. Functional outcomes were additionally stratified by time from injury to surgery (Table 6). Patients undergoing surgery within 6 months demonstrated greater mean improvements in ROM and MRC scores compared to patients undergoing delayed intervention. However, postoperative functional improvement was also observed in patients undergoing surgery greater than 6 months after injury. Only patients with a minimum two-year follow-up were included in the ROM and MRC score analysis. Notably, because a redundant radial nerve branch could NOT be isolated for one patient intraoperatively, the procedure was aborted, leading to no change in his ROM and strength post-operatively (and excluded from results analysis).

Table 2:

Summary of Functional Outcome Improvements Post-Nerve Transfer

	Average Pre-Surgery	Average Post-Surgery	Average Δ	t-test p-value
MRC	1.55 ± 0.82	4.36 ± 0.81	2.82 ± 1.33	p < 0.01
Forward Flexion	43.18° ± 23.05°	151.36° ± 30.99°	108.18° ± 44.17°	p < 0.01
Abduction	40.09° ± 19.85°	135.00° ± 34.57°	94.91° ± 41.58°	p < 0.01
External Rotation	15.56° ± 25.55°	54.50° ± 14.03°	36.67° ± 27.04°	p < 0.01

Figure 2:

Mean pre- and post-operative ROM

Table 3:

Comparison of gain in ROM from pre-op to final follow-up visit between Group A (end-to-end transfer) and Group B (end-to-side transfer)

	Group A Mean ± SD (Range, Median)	Group B Mean ± SD (Range, Median)	p-value
ΔForward Flexion	92.00 ± 53.81° (0–135°, 105°)	121.67 ± 33.27° (60–150°, 132.5°)	0.29
ΔAbduction	72.80 ± 45.07° (0–115°, 74°)	113.33 ± 30.61° (60–150°, 122.5°)	0.11
ΔExternal Rotation	39.00 ± 33.62° (−20–60°, 50°)	33.75 ± 20.56 (10–60°, 32.5°)	0.79

Table 6:

Functional Outcomes Stratified by Time from Injury to Surgery

	≤6 Months (n=7)	>6 Months (n=4)	p-value
Average Δ MRC	3 ± 1.15	2.5 ± 1.73	0.63
Average Δ Forward Flexion (°)	115.00 ± 30.00	96.25 ± 66.38	0.62
Average Δ Abduction (°)	104.29 ± 31.42	78.50 ± 56.79	0.45
Average Δ External Rotation (°)	37.00 ± 19.24	36.25 ± 38.16	0.97

MEP immunofluorescence analysis:

MEPs were visualized in all deltoid muscle samples collected (n=8), even in biopsies analyzed prior to optimization of tissue visualization protocols (in 2020). Importantly, MEPs were encountered in 4 patients beyond 6 months from injury to surgery/biopsy. However, the MEPs that were present exhibited clear signs of degeneration in all patients. (Figure 3) Among the 3 samples that were imaged after tissue cleaning optimization, the average percentage of abnormal MEPs (plaque and intermediate morphologies) was 88.20% (range, 80–100%). Meanwhile, the average percentage of healthy MEPs (pretzel morphology) was only 11.80% (range, 0–20%). Average number of MEPs in each biopsy sample was 7.67 (range, 5–13), and the average percentage of MEPs with intact nerve terminals was 56.00% (range, 0–100%) (Table 4).

Figure 3:

Muscle data from a patient with isolated axillary nerve injury. (A) Gross atrophy of deltoid is apparent on clinical exam at 7 months post-injury. (B-E) Immunofluorescence of MEPs at 20x magnification. Red signal represents MEPs and is stained with AChR-α. Green signal represents the nerve terminal and is stained with neurofilament/synaptophysin. (B-C) Pretzel MEPs in uninjured triceps with intact nerve terminal. (D-E) Intermediate MEPs in injured deltoid.

Table 4:

Patient injury duration and Analysis of MEP Morphology

Study ID	Time from injury to surgery (months)	Percentage of healthy MEPs (pretzel)	Percentage of unhealthy MEPs (intermediate + plaque)	Percentage of unhealthy MEPs (plaque)	Percentage of unhealthy MEPs (intermediate)	Percentage of Innervated MEPs	Number of MEPs
5*	7	0.00%	100.00%	20.00%	80.00%	100%	5
6*	5	15.39%	84.61%	30.76%	53.85%	69.23%	13
9**	3	20.00%	80.00%	20.00%	60.00%	0.00%	5

^*Biopsy samples were imaged via Keyence BZ-X810 inverted fluorescence phase contrast microscope

^**Study ID 9’s biopsy sample was imaged via two-photon excitation microscopy but underwent the same tissue cleaning optimization implemented in 2020 as study IDs 5 and 6.

Based on his clinical course, one patient received three surgeries, and 3 muscle biopsies were possible.⁵ (Table 5) The pre-nerve transfer biopsy contained only 20% of MEPs with pretzel morphology, whereas biopsies at 7 and 15 months post-transfer revealed 62.5% and 83.4% of MEPs with pretzel morphology, respectively (Table 5). Furthermore, the percentage of MEPs with an intact nerve terminal improved from 0% pre-transfer to 75% and 83% at 7- and 15-month post-nerve transfer, respectively. Each subsequent biopsy demonstrated improvements in MEP morphology and innervation status after undergoing nerve transfer. (Figure 4)

Table 5:

MEP morphology and innervation status in a patient with 3 sequential biopsies

Biopsy Number	Time post-nerve transfer (months)	Percentage of Unhealthy MEPs (intermediate + plaque)	Percentage of healthy MEPs (pretzel)	Total number of MEPs	Percentage of MEPs with intact nerve terminals
1	0	80%	20%	5	0%
2	7	37.50%	62.50%	8	75%
3	15	16.60%	83.40%	6	83.3%

Figure 4:

MEPs from patient with three sequential biopsies. Red signal represents MEPs and is stained with AChR-α. Green signal represents the nerve terminal and is stained with neurofilament/synaptophysin. (A-F) MEPs from pre-nerve transfer biopsy demonstrating absence of nerve terminals. (G-L) MEPs from 7 months post-nerve transfer biopsy demonstrating rescue of nerve terminals and MEP morphology. (M-R) MEPs from 15 months post-nerve transfer biopsy demonstrating maintenance of healthy MEPs with intact nerve terminals.

MEPs, EMGs and postoperative recovery:

2 patients in the muscle biopsy cohort had pre- and post-nerve transfer EMGs, both of which were done 1-year post-op. Both patients had MEP persistence at the time of nerve transfer and initial muscle biopsy. Postoperatively, both patients exhibited signs of increased innervation by EMG, evidenced by increased polyphasic units, appearance of nascent potentials, and decreased fibrillation potentials.

Discussion

Axillary nerve injuries are devastating, with limited surgical options.^1,33 Current literature on postoperative outcomes following nerve transfers in the upper extremity varies significantly. Desai et al.⁹ found that among 27 patients who received nerve transfers for brachial plexus or isolated axillary nerve injury, 4 achieved an M5 score, 13 achieved an M4 score, and average postoperative abduction was 114°. Wells et al.³⁷ reported improvement in 18/30 patients with axillary nerve injuries following radial nerve transfer (defined as an increase > 40° in shoulder abduction and M3 or greater strength). However, Wells et al.’s criteria for clinical improvement does not fully capture functional recovery as patients with M3 score and < 100° abduction will not be able to perform any overhead activities. While current literature suggests that outcomes from nerve transfers may not be significantly different from nerve grafts, most studies are underpowered with incomplete data.^32,40 Although palliative surgeries (shoulder arthrodesis and tendon transfer) offer pain relief, they do so often at the expense of a functional upper extremity.^11,15

Our clinical outcomes suggest that partial radial-to-axillary nerve transfer should be considered as an index reconstructive procedure for patients with isolated axillary nerve injuries who fail to demonstrate meaningful recovery following an initial period of observation. This study focuses exclusively on isolated axillary nerve injuries treated with a single radial-to-axillary nerve transfer across both subacute and chronic presentations, allowing a more precise characterization of postoperative shoulder recovery. In contrast, most prior studies have combined isolated axillary nerve injuries with broader brachial plexus reconstruction cohorts, limiting interpretation of outcomes specific to isolated axillary nerve dysfunction.^{9, 23, 37}. Although previous studies have demonstrated meaningful postoperative improvement following radial-to-axillary nerve transfer, recovery to near-normal deltoid strength and shoulder function remains the exception rather than the rule. Moreover, interpretation of these outcomes is confounded by substantial clinical heterogeneity, as most published series combine isolated axillary nerve injuries with more complex brachial plexus reconstruction cohorts. Furthermore, most surgeons have historically employed Leechavenvongs et al.’s²⁴ technique. The technique used in our cohort includes several modifications. 1) The donor nerve branch was chosen based on intraoperative nerve stimulation rather than tracing to the long head of the triceps. This ensures that the donor nerve is a radial nerve branch that can be harvested with minimal donor morbidity function. 2) The inferior teres major fascia was released without injuring the underlying muscle or partially detaching its humeral insertion. Our modification expedites postoperative recovery and preserves internal rotation. 3) All transfers were tested to verify a tension-free surgical nerve coaptation by positioning the patient’s arm in full forward flexion, abduction, and external rotation intraoperatively. This extra step ensures a tension-free repair that creates a favorable environment for nerve regeneration and protects the axillary nerve from further stretch injuries. While the independent contribution of these technical modifications cannot be determined in this study, these differences may contribute to the improved results that display the possibility of recovery to nearly-normal ROM and muscle strength, without measurable donor-site morbidity. Accordingly, intraoperative functional assessment of the donor nerve was performed to confirm donor redundancy before harvest and to preserve critical distal upper extremity motor function. Although previous clinical series have generally reported minimal or no clinically apparent donor-site morbidity following harvest of the long head triceps motor branch, recent objective isokinetic analyses suggest that subtle donor deficits including a mean 23% reduction in strength and a 60% increase in fatigue may be underrecognized. These findings further support the use of intraoperative functional assessment when selecting a donor fascicle.³¹

Remarkably, in our cohort, nerve transfers proved useful for some patients who underwent surgery > 6 months after nerve injury. Recovery following nerve transfer may be attributable to the persistence of MEPs in human muscle beyond the historically accepted timeline.^3,4 Our analysis of deltoid muscle biopsies in 4 patients who were greater than 6 months post-injury revealed MEPs in all 4. Although morphometric analysis revealed significant degeneration of MEPs, their continued presence along with some intact nerve terminals suggested that these patients were favorable candidates for nerve transfer, despite being beyond the accepted treatment window. This study expands on prior reports that MEPs can persist in denervated human muscles at long intervals after PNI, and that patients with surviving MEPs can exhibit meaningful functional recovery after delayed nerve transfer reconstructive surgery.^3,4,5,16 This finding further motivates the development of objective, quantitative assessments of functional recovery potential after surgical nerve repair, which can guide decision-making about delayed nerve transfer surgeries.

We provide the first objective data on changes in MEP morphology after nerve injury and reinnervation. One of our patients received 3 sequential biopsies: pre-nerve transfer (3 months post-injury), 7 months post-nerve transfer, and 15 months post-transfer. While his pre-transfer biopsy demonstrated morphological degeneration, by the final biopsy, the percentage of MEPs with intact nerve terminals improved from 0% to 83.3%, and the percentage of pretzel (healthy) MEPs improved from 20% to 83%. These sequential biopsy findings suggest that nerve transfers can prevent further MEP degeneration, rescue MEP morphology, and restore the nerve terminals that innervate MEPs. Of note, patients with multiple surgeries and biopsies showed that improved ROM was associated with recovery of MEP measures. Thus, developing objective criteria to assess reinnervation competence could be crucial in making informed decisions about delayed nerve transfer surgeries.

All patients in this series displayed gross preoperative deltoid atrophy with significantly abnormal EMGs and clinical findings consistent with axillary nerve injury (without meaningful reinnervation or clinical recovery before surgical intervention). One cardinal sign of denervation is the appearance of fibrillation potentials, which typically appear in denervated muscles 1–4 weeks post-nerve injury.³⁹ Increasing fibrillation potential grades correlate with increased severity of nerve damage.^8,36 Before surgical intervention, 12 patients demonstrated fibrillation potentials. EMGs also provided data regarding denervation and signs of reinnervation. Motor unit recruitment is often used to map out the severity of nerve lesions— the greater the reduction in recruitment, the more severe the nerve injury.^7,13 In our cohort, 14/16 patients demonstrated significant reductions in motor unit recruitment. Another EMG measure involves MUPs, which assess innervation status; zero MUPs represent severe muscle atrophy and neural degeneration, while reinnervation is evidenced by long-duration, high-amplitude MUPs.¹⁸ In our studied group, 11/16 patients’ EMGs demonstrated abnormal MUPs, and 4 with zero MUPs. Finally, in addition to motor unit potentials, nascent potentials are markers of reinnervation. Nascent potentials are low-amplitude, polyphasic signals that appear only when axonal regeneration has begun. Thus, nascent potentials are only present in patients several months post-injury.¹³ Initial nascent potentials are small and incapable of generating clinically detectable movements but represent early signs of reinnervation.¹³ In our cohort, 5 patients had many nascent potentials, suggesting some early-stage reinnervation in these patients, while 8 patients had no detectable nascent potentials.

Despite objective evidence of axillary nerve injury and deltoid denervation, 14/16 patients showed significant post-surgery functional improvements, including one who had a nerve transfer > 120 months post-injury and 6 who had nerve transfers >6 months post-injury. Functional outcomes were additionally stratified by time from injury to surgery (Table 6). Patients treated within 6 months generally demonstrated greater improvements in ROM and MRC scores. However, meaningful postoperative functional improvement remained possible in delayed presentations and surgical treatments. The recovery of ROM/MRC scores following nerve transfer across a broad range of ages suggest that prolonged time from injury may not preclude functional recovery following radial-to-axillary nerve transfer. Furthermore, the persistence of MEPs observed on deltoid biopsy analysis may provide biologic context supporting the recovery potential observed in delayed presentations. Although our data might be interpreted to suggest that end-to-side produced better ROM than end-to-end coaptation, this difference was not statistically significant. Thus, a more appropriate conclusion is that end-to-side transfer produces no worse outcomes than an end-to-end coaptation. Additionally, end-to-side transfer does not preclude possible continued recovery of the injured axillary nerve following surgery, as it is left in continuity, whereas it must be fully transected for an end-to-end coaptation. This strategy may be particularly valuable in the subacute treatment setting, when residual axillary nerve recovery remains possible. By preserving native axillary nerve continuity while augmenting reinnervation through the donor nerve, it allows earlier surgical intervention without precluding the possibility of continued spontaneous neurologic recovery.

The strengths of this study include its diverse injury types, broad patient demographics, consistent surgical technique, and objective measurements of target end-organ response. Our study is one of few to assess MEP structural changes before and after reinnervation and integrates clinical and electrophysiological objective data into outcomes analysis. Additionally, all surgical procedures were performed by a single surgeon, eliminating surgeon-specific factors that may confound results.

Limitations of this study include its relatively small sample size, lack of a control group, and patient loss to follow-up. Also, the lack of subgroup analysis by sex/gender and patient ethnicity data may limit the generalizability of the study’s findings. Despite this, 11 patients who were followed for a minimum of 2 years were rigorously assessed for donor-site morbidity as well as functional ROM and strength testing. While muscle biopsies are an ongoing, prospective study, all follow-up data for this study was analyzed retrospectively. The relatively small sample size due to the relatively low incidence of PNIs²², was mitigated by collecting data over eight years, resulting in a larger cohort of patients. Furthermore, our mean pre-operative versus final follow-up ROM demonstrated a large effect size, increasing the statistical power of our study.

Conclusion:

Deltoid function is paramount for upper extremity movement, strength, and stability^12,19, especially in older patients, where the deltoid is often the most powerful muscle left in the shoulder. Thus, if the deltoid is damaged, patients are typically relegated to minimal shoulder function.^1,33 The approach presented in this study, in which partial radial-to-axillary nerve transfer is employed as the index reconstructive procedure for isolated axillary nerve injuries in both subacute and chronic settings, offers the potential for meaningful restoration of shoulder function. In this cohort, patients demonstrated substantial improvements in shoulder range of motion and deltoid strength following nerve transfer, including selected patients treated beyond the traditional 6-month treatment window. Importantly, persistence of motor endplates within chronically denervated deltoid muscle was observed even in delayed presentations, providing biologic support for the recovery potential demonstrated in this series and suggesting that selected patients may remain candidates for successful nerve reconstruction beyond traditionally accepted timeframes. When an appropriate donor radial nerve branch can be identified in patients with an isolated axillary nerve injury, surgeons should strongly consider a partial radial-to-axillary nerve transfer for the index treatment procedure.

Data Availability:

Anonymized data not published within this article will be made available by request from any qualified investigator.