Contralateral C7 nerve transfer combined with human acellular nerve allograft as a viable strategy for spastic upper limb paralysis

Abstract

Background

Peripheral nerve surgery is a potential treatment for chronic spastic hemiplegia, but the role of contralateral C7 nerve transfer combined with human acellular nerve allograft remains to be explored. This study aimed to investigate the functional outcomes of contralateral C7 nerve transfer combined with human acellular nerve allograft for spastic upper limb paralysis.

Methods

From January 2020 to December 2023, 53 patients with unilateral spastic upper limb paralysis completed a 12-month follow-up. 17 patients underwent contralateral C7 nerve transfer combined with human acellular nerve allografts, while 36 received rehabilitation alone. The primary outcome was the change in the Fugl-Meyer Assessment. Safety outcomes included adverse events and changes in muscle strength and motor–sensory function assessment of the arm and hand on the side of the donor C7 nerve.

Results

The overall Fugl-Meyer Assessment increased by 15.88 ± 3.54 in the surgery group and 2.36 ± 2.34 in the rehabilitation group (difference, 13.52, P < 0.001). Spasticity improvements were observed on the Modified Ashworth Scale for various muscle groups (P < 0.001). Adverse events related to the donor nerve included mild numbness in the radial three digits, slightly weakened triceps brachii strength, and tolerable peripheral neuropathic pain. No other adverse event relative to the bilateral brachial nerve occurred except for the C7 nerve section, and all events resolved within 3 months for all patients.

Conclusion

Our study suggests that the combination of the contralateral C7 nerve transfer and the human acellular nerve allograft may be a viable treatment option for individuals experiencing long-term spastic upper limb impairment following chronic cerebral hemisphere injury.

Trial registration: This clinical study was registered with the Chinese Clinical Trial Registry, and the registration number is ChiCTR2500099694

Supplementary Information

The online version contains supplementary material available at 10.1186/s40001-025-03770-2.

Introduction

Stroke, cerebral palsy, and traumatic brain injury now cause upper limb spastic paralysis for an increasing number of individuals, with a third resulting in severe disabilities that impose substantial social and economic repercussions [1]. Conventional rehabilitation therapies are effective in the early stage but yield limited benefits once the condition enters the plateau phase at ≥ 1 year post-injury [2], leaving an unmet clinical need for effective interventions tailored to this stage.

Contralateral cervical seventh nerve (CC7) transfer, originally developed for brachial plexus root avulsion [3], has emerged as a promising strategy for upper limb spastic paralysis. Clinical evidence confirms its therapeutic potential, with significant motor function improvements reported postoperatively [4, 5]. Nonetheless, a significant challenge encountered during the procedure is the adequacy of the lengths of the patient's bilateral C7 nerves to establish an anatomical pathway for tension-free suturing on both sides [6]. To address this, autologous sural nerve grafts remain the conventional solution for C7 length deficits, but impose substantial donor-site trauma and persistent sensory impairment.

To address both the length limitation of CC7 nerves and the drawbacks of autologous grafts, the human acellular nerve allograft (ANA) would be a viable solution. Our team-developed ANAs have been clinically validated for safety and efficacy in repairing 3–5 cm short nerve defects over decades [7–9]. Notably, the feasibility and effectiveness of ANAs in CC7 transfer for patients with spastic paralysis remain unreported.

Herein, we conducted a cohort study with the rehabilitation group as the control, aiming to investigate the functional outcomes of contralateral C7 nerve transfer combined with human acellular nerve allograft for spastic upper limb paralysis.

Methods

This observational cohort study was approved by the institutional review board of the First Affiliated Hospital of Sun Yat-sen University. From January 2020 to December 2023 in our department, 226 patients suffering from stroke, brain trauma, encephalitis, or cerebral palsy were screened, and 164 patients were ruled out. Inclusion criteria were defined as: spastic hemiplegia following central neurologic injury with FMA score 20–50 points; aged 20–60 years with no gender restrictions; having received regular rehabilitation therapy for at least 1 year with no further improvement; and central neurologic injury limited to the contralateral hemisphere. The exclusion criteria were: presence of deformity or severe stiffness of upper limb joints; history of other peripheral nerve surgeries; evidence of progressing brain injury; and systemic diseases precluding the ability to tolerate surgery. Finally, 20 patients who underwent CC7 nerve root transfer combined with ANAs were enrolled in the surgery group. Additionally, 42 patients who declined surgery were enrolled in the rehabilitation group. A standardized rehabilitation program centered on physiotherapy and occupational therapy was delivered to all participants, including manual stretching, active single-joint movement training, and occupational training. Both groups received rehabilitation from the same team of therapists at the same training intensity and duration over 12 months, including 3 h per day, 5 days weekly for the 1st–3rd months, 3 days weekly for the 4th–6th months, and 2 days weekly for the 7th–12th months. Preoperative radiography, brachial plexus MRI, and several routine examinations were conducted to exclude any contraindication to surgery. Brain MRI was performed to verify that the original brain lesion was limited to a single cerebral hemisphere and non-progressive. Preoperative physical examination including Fugl-Meyer assessment, Modified Ashworth Scale, Action Research Arm Test, manual muscle testing, and measurement of joint motion range. The standardized follow-up evaluations for all patients enrolled were performed at 6th week, 3rd month, and every 3 months until 1 year follow-up. The evaluator, who performed all outcome assessments, was meticulously blinded to the treatment allocation and was specifically instructed to avoid identifying patients based on surgical scars or any other treatment-related indicators. Clinical features of a typical patient before and after the operation are detailed in Supplemental Video 1.

Surgical techniques

The surgical procedures adhered to our previously published methods [9]. Patients were placed in a supine position with their neck extended. The brachial plexus of spastic side was explored through a supraclavicular transverse incision about 6 cm (Fig. 1A). Upper trunk, middle trunk (C7), and lower trunk of brachial plexus were carefully dissected and identified according to anatomical structures and intraoperative electrophysiology (Fig. 1B). The C7 nerve was dissected proximally and transected near the intervertebral foramen after 2% lidocaine nerve block. On the contralateral side (healthy side), a similar incision was made. Using the same way to explore the CC7 nerve root and then carefully dissected distally reaching the junctures where the anterior division meets the lateral cord and the posterior division converges with the posterior cord. The CC7 nerve root was transected distally at the division terminus under nerve block. Then, the CC7 nerve root was dissected to the proximal end to the level of the intervertebral foramen, and the length of the CC7 nerve root was recorded (Fig. 1C). The CC7 nerve root was pulled to the medial side of scalenus anterior through the tunnel between the scalenus anterior and the vertebral body. The transverse tunnel was established between the esophagus and the longus colli by blunt separation, and a silicone tube with a diameter of 6 mm and a length of 6 cm was temporarily placed in this tunnel (Fig. 1D), to transfer the CC7 nerve root to the affected side. The CC7 nerve root was sutured with the human acellular nerve allograft (Nerve Bridge, ZDMED-5060, Guangzhou, China) by end-to-end epineurium suture technique with 8–0 Prolene sutures. Then, the CC7 nerve root combined with the acellular nerve allograft was transferred to the affected side through the prevertebral tunnel, and at the same time, the silicone tube removed. After removal of the redundant acellular nerve allograft (Fig. 1F), the C7 nerve of spastic side was sutured with the human acellular nerve allograft without tension (Fig. 1G). Finally, the surgical incision was closed by interrupted suture (Fig. 1H). After the operation, we use a sling to make sure the paralyzed upper extremity was partially immobilized in shoulder adduction for 6 weeks. A brief video of operation protocol is in Supplemental Video 2.

Fig. 1.

Surgical process: A: Surgical illustration of ANA combined with CC7 nerve transfer. B: Exploration of the brachial plexus of spastic side; the intraoperative photograph shows marked upper trunk (blue sling), middle trunk (C7) (yellow sling), and phrenic nerve (rubber band). C: The CC7 nerve root was transected at the most distal end of the divisions, and the length of the harvested CC7 nerve root was measured. D: a silicone tube (white arrow) with a diameter of 6 mm and a length of 6 cm was temporarily placed in the tunnel. E: The original length of the acellular nerve allografts. F: The redundant acellular nerve allografts of about 3 cm was removed. G: The acellular nerve allografts were anastomosed to the C7 root in the spastic side. H: The bilateral supraclavicular incisions were closed with sutures

Clinical evaluation

Fugl-Meyer assessment

The Fugl-Meyer Assessment (FMA) was designed to assess recovery in stroke patients and consisted of 33 items, each rated on a scale of 0–2. The scale specifically included the "upper limb", "wrist", "finger" functional domains, and motor coordination (total score: 0–66; higher scores indicated better functional recovery) [10].

Muscle spasticity

The Modified Ashworth Scale (MAS) measured spasticity at each joint on a scale of 0 to 5, with higher values indicating more severe spasticity. Patients were instructed to relax and placed in a supine position. Depending on the muscle group being assessed, the joint was positioned for maximal flexion or extension [11].

Motor function assessment

Motor function was assessed using the Action Research Arm Test (ARAT), a standardized measure designed to evaluate upper limb function in individuals with hemiparesis. The ARAT consisted of 19 items categorized into four subscales: grasp, grip, pinch, and gross arm movements. Each item was scored from 0 to 3, with higher scores indicating better motor function [12].

Statistical analysis

Descriptive statistics were used to characterize the baseline demographic and clinical profiles of all participants. For continuous variables, independent samples t tests were applied to compare intergroup differences at baseline. The primary outcome defined as the change in FMA score was analyzed via analysis of covariance (ANCOVA); key baseline covariates were included in the model for confounding adjustment. Pearson correlation analysis, Spearman’s rank correlation test, and Kendall’s tau test were applied to explore relationships between covariates and outcomes. Secondary outcomes, including changes in MAS, ARAT scores, and active range of motion were compared between groups using independent samples t tests and Chi-square tests, with selection depending on continuous or categorical data; Fisher’s exact test was used for categorical variables with small sample size and theoretical expected frequency < 5.

Patients lost to follow-up were excluded from the primary outcome analysis, and a sensitivity analysis was performed using worst-case scenario imputation. A post hoc power analysis was conducted to confirm the adequacy of the sample size for detecting clinically meaningful effects. Normality via the Shapiro–Wilk test, homoscedasticity via Levene’s test, and linearity via Pearson correlation analysis were verified for parametric analyses. The Bonferroni correction was applied for multiple pairwise comparisons.

All main outcome measures were reported with 95% confidence intervals (CIs) to reflect result precision. A two-tailed P value < 0.05 was considered statistically significant. All statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS) version 24.0 (IBM Corp).

Results

During follow-up, the surgery cohort decreased by 3 participants, and the rehabilitation cohort by 6 (specific reasons for participant attrition are detailed in Fig. 2). Consequently, the final analysis included 17 participants in the surgery group and 36 in the rehabilitation group. The baseline characteristics of patients in the surgery group were comparable to those in the rehabilitation group. The causes of cerebral injury included stroke, traumatic brain injury, cerebral palsy, and encephalitis (Table 1). There were no significant differences in the characteristics of the patients at baseline between the groups. The mean interval from the original neurologic injury was 9.66 years in the surgery group and 6.61 years in the control group. Though the interval appeared to be a potential confounder, ANCOVA’s common slope assumption was validated by testing its interaction with treatment group, which yielded a non-significant result (P > 0.05). Pearson, Spearman’s rank, and Kendall’s tau analyses further ruled out linear/non-linear associations between the interval and the primary outcome.

Fig. 2.

Trial profile. Surgery group (3 dropouts): 2 underwent additional tendon transfer surgery; 1 died of an unrelated accident. Rehabilitation group (6 dropouts): 1 received nerve transection surgery; 5 underwent tendon transfer surgery. FMA = Fugl-Meyer Assessment

Table 1.

Characteristics of the patients at baseline

Characteristic	Surgery group (N = 17)	Rehabilitation group (N = 36)
Male sex—no. (%)	12(70.58)	25(69.44)
Age-yr	37.12 ± 13.90	39.36 ± 11.84
Side of paralyzed hand-no. (%)
Left	10(58.82)	20(55.56)
Right	7 (41.18)	16(44.44)
Cause of injury-no. (%)
Stroke	9 (52.94)	20(55.56)
Traumatic brain injury	3 (17.65)	4 (11.11)
Cerebral palsy	3 (17.65)	8 (22.22)
Encephalitis	2 (11.76)	4 (11.11)
Time from original neurologic injury to entry into trial-yr	9.66 ± 11.02	6.61 ± 9.30
Fugl-Meyer assessment (FMA)	33.00 ± 5.88	33.08 ± 8.12
Action research arm test (ARAT)	20.71 ± 9.95	22.67 ± 10.50
Modified Ashworth Scale*
Shoulder extension	0(1), 1(6), 1 + (4), 2(5), 3(1), 4(0)	0(3),1(9),1 + (11),2(10),3(3),4(0)
Elbow extension	0(1), 1(0), 1 + (2), 2(11), 3(3), 4(0)	0(2),1(3),1 + (9), 2(15),3(7),4(0)
Forearm rotation	0(1), 1(1), 1 + (4), 2(9), 3(2), 4(0)	0(2),1(2),1 + (10),2(15),3(7),4(0)
Wrist extension	0(1), 1(1), 1 + (1), 2(7), 3(7), 4(0)	0(1),1(4),1 + (6), 2(16),3(9),4(0)
Fingers extension	0(2), 1(1), 1 + (5), 2(5), 3(3), 4(1)	0(1),1(2),1 + (11),2(13),3(9),4(0)
Range of motion-degrees
Shoulder	120.59 ± 55.59	124.58 ± 50.28
Elbow	104.12 ± 37.63	105.56 ± 34.68
Forearm rotation	52.35 ± 55.96	55.56 ± 46.07
Wrist	39.41 ± 51.53	40.56 ± 44.33

^*The Modified Ashworth Scale assesses spasticity across five joints, with scores ranging from 0 to 5 for each joint. The initial number in each row represents the score, while the number in parentheses denotes the count of patients of that score

The mean improvement in the FMA score from baseline to the 12 months was significantly greater in the surgery group, with a change of 15.88 ± 3.54, compared to the control group, which exhibited a change of 2.36 ± 2.34 (Shapiro–Wilk test confirmed normality, Levene’s test confirmed homoscedasticity, P > 0.05; between-group difference: 13.52; 95% CI: 11.46–15.58; P < 0.001) (Table 2). Notably, a significant increase in the FMA score was observed between the 6th and 9th month in the surgery group, with a change of 8.353 (95% CI 0.4548 to 16.25, P = 0.0318) (Fig. 3A).

Table 2.

Primary and secondary outcomes at baseline and month 12

Outcome	Surgery group (N = 17)	Rehabilitation group (N = 36)	Mean difference (95%CI)	P value
Primary outcome
Change in total Fugl-Meyer score from baseline to month 12	15.88 ± 3.54	2.36 ± 2.34	13.52 (11.46 to 15.58)	P < 0.001
Secondary outcomes
Change in Action research arm test from baseline to month 12	6.88 ± 2.98	1.58 ± 2.30	5.30 (3.62 to 6.98)	P < 0.001
Change in Modified Ashworth Scale score from baseline to month 12*
Shoulder extension	0(1), −1(7), −2(5), −3(4), −4(0)	0(25), −1(7), −2(4), −3(0), −4(0)	\	P < 0.001
Elbow extension	0(1), −1(3), −2(1), −3(12), −4(0)	0(22), −1(11),−2(3), −3(0), −4(0)	\	P < 0.001
Forearm rotation	0(1), −1(7), −2(7), −3(2), −4(0)	0(28), −1(8), −2(0), −3(0), −4(0)	\	P < 0.001
Wrist extension	0(1), −1(1), −2(11),−3(4), −4(0)	0(29), −1(6), −2(1), −3(0), −4(0)	\	P < 0.001
Fingers extension	0(2), −1(2), −2(7), −3(5), −4(1)	0(29), −1(7), −2(0), −3(0), −4(0)	\	P < 0.001
Change in range of motion from baseline to month 12-degrees
Shoulder	18.24 ± 14.57	4.31 ± 7.67	13.93 (7.82 to 20.04)	P < 0.001
Elbow	33.53 ± 26.85	3.89 ± 6.88	29.64 (20.14 to 39.14)	P < 0.001
Forearm rotation	29.41 ± 19.83	4.17 ± 8.41	25.25 (17.50 to 32.99)	P < 0.001
Wrist	40.59 ± 21.64	2.78 ± 7.02	37.81 (29.87 to 45.75)	P < 0.001

\ denotes not applicable. The Modified Ashworth Scale assesses spasticity across five joints, with original ordinal grades of 0, 1, 1 +, 2, 3, and 4. These grades were converted to six numerical grades (0–5) for the convenience of calculating grade changes. A negative value indicates a reduction in spasticity from the baseline to the 12-month follow-up assessment. The number in parentheses denotes the count of patients experiencing that specific change. The alterations in MAS scores from baseline to the 12th month were statistically analyzed using Fisher’s exact test

Fig. 3.

A: The Fugl-Meyer assessment scores. B: Modified Ashworth Scale in the surgery group during 1-year follow-up. * Significant difference between 6th month and 9th month (P < 0.05)

Improvements in spasticity, as measured by MAS from baseline to the 12-month endpoint, consistently indicated superior outcomes for the surgery group across all assessed joints. Of all evaluated muscles in the surgery group, 7.06% showed no change in muscle tone, whereas this proportion was as high as 92.36% in the rehabilitation group. Conversely, 69.41% of muscles in the surgery group achieved a ≥ 2-grade reduction in MAS, compared with only 5.56% in the rehabilitation group. Statistically significant reductions in muscle tone were observed for shoulder extension (P < 0.001), elbow extension (P < 0.001), forearm supination (P < 0.001), wrist extension (P < 0.001), and finger extension (P < 0.001) (Table 2). Furthermore, no instances of muscle tone rebound in any upper limb segments were noted throughout the 1-year follow-up period, as documented by the MAS scores (Fig. 3B). The mean changes in the ARAT score from baseline to the 12th month were 6.88 ± 2.98 in the surgery group versus 1.58 ± 2.30 in the rehabilitation group with a between-group difference of 5.30 (95% CI 3.62 to 6.98; P < 0.001) (Table 2). The active range of motion demonstrated significant improvements in the surgery group over the 12-month period, with increase of 18.24 ± 14.57 degrees in the shoulder, 33.53 ± 26.85 degrees in the elbow, 29.41 ± 19.83 degrees in the rotation of the forearm, and 40.59 ± 21.64 degrees in the wrist. Conversely, the rehabilitation group exhibited mean changes of 4.31 ± 7.67 degrees for shoulder, 3.89 ± 6.88 degrees for elbow, 4.17 ± 8.41 degrees for forearm rotation, and 2.78 ± 7.02 degrees for wrist. The differences in the range of motion enhancements between the surgery and rehabilitation groups were statistically significant for all joint assessments (P < 0.001) (Table 2). All aforementioned continuous variables satisfied normality assumptions via Shapiro–Wilk test and homoscedasticity via Levene’s test (P > 0.05), and Bonferroni correction was applied for multiple comparisons of these secondary outcomes, with all between-group differences remaining statistically significant after correction (P < 0.001).

The average time of operation is 3.64 ± 0.39 h. The mean length of C7 nerve is 54.28 ± 2.94 mm on the donor side, and the average allograft Length is 36.94 ± 4.49 mm. Adverse events that were related to the operative treatment in the surgery group comprised pain in 4 patients on the healthy side or paralyzed upper limb. This pain could be cured by oral medications (Pregabalin, 75–150 mg/day). The pain of 3 patients was relieved completely within 2 months after surgery, which of another patient was also eased during 3 months after surgery. The adverse events on the donor nerve side were characterized by mild numbness of the thumb, index, and middle fingers in 16 patients and a slight reduction in triceps brachii strength in 14 patients. The majority of the above-mentioned adverse events ameliorated within 6 weeks after surgery. However, the numbness of index finger in one patient gradually healed until 3 months after surgery. By the 6th month postoperatively, no changes in sensorimotor function related to the donor C7 nerve were detected in all surgical patients, which was assessed by neurological examination and muscle power evaluation (Table 4).

Table 4.

Adverse Events in Surgery Group (N =17)

Complications related to treatment-no. of events	Baseline	Week 6	Month 3	Month 6	Month 9	Month 12
Bleeding	0	0	0	0	0	0
Infection	0	0	0	0	0	0
Allograft rejection	0	0	0	0	0	0
Foreign-body sensation when swallowing	0	0	0	0	0	0
Pain(Healthy or paralyzed upper limb)	0	4	0	0	0	0
Decrease in triceps brachii strength	0	14	0	0	0	0
Numbness of digits	0	16	1	0	0	0

Discussion

Spasticity is a significant factor contributing to motor dysfunction in patients with cerebral injury [13]. Traditional treatments include Botulinum Toxin injection, baclofen treatment, selective spinal posterior rhizotomy, and high selective peripheral neurotomy. While these approaches have respective merits in specific clinical scenarios, they share a critical limitation of high spasticity recurrence [14]. In this study, no significant recurrence of muscle tone was observed in either early or late postoperative phases over the 12-month follow-up. Our primary outcome, FMA score, showed a significant improvement in the surgery group (15.88 ± 3.54) at the 12-month follow-up, compared with the rehabilitation group (2.36 ± 2.34), which exceeds the established minimal clinically important difference (MCID) of 5.25 points for excellent arm function gains among patients with chronic cerebral injury sequelae [15].

The therapeutic mechanism of CC7 nerve transfer for spastic upper limb paralysis remains incompletely understood. In recent years, unilateral brain injury has been shown to induce collateral sprouting of the unaffected-side corticospinal tract at the spinal level, a process thought to contribute to affected limb motor recovery [16–18]. Additionally, CC7 nerve transfer is hypothesized to enhance this sprouting by modulating sensory input from the affected limb to the unaffected cerebral hemisphere [19]. In our study, motor function improvements in the surgery group emerged around the 6th-to-9th postoperative month and persisted until the 12th month, consistent with the timeline of nerve fiber regeneration from the unaffected hemisphere. Notably, BOLD-fMRI at 12 months revealed activation of core motor areas in both cerebral hemispheres during affected upper limb movement in some patients. These findings are compatible with neural plasticity as a potential mechanism, though specific processes require further exploration [20, 21].

While our study presented significant upper extremity functional gains in spastic hemiplegia, precise patient selection is critical to optimizing clinical efficacy. Ideal candidates, based on our clinical experience, should meet core criteria: ≥ 1 year of consistent post-injury rehabilitation with plateaued functional recovery; upper extremity spasticity manifesting as predominant hypertonia, preserved residual muscle strength and minimal passive movement limitation; and intact contralateral cerebral hemisphere as well as bilateral brachial plexus lower motor neuron pathways. However, consensus on CC7 transfer’s clinical indications remains lacking, necessitating refinement of candidate selection protocols. AI-enhanced clinical decision support systems, which offer a viable option through the integration of multi-dimensional clinical data, can quantify patients’ likelihood of benefit and standardize candidate selection via objective data-based stratification [22]. The combination of AI-assisted decision-making with CC7 nerve transfer holds notable research value and considerable clinical potential for future application.

Postoperatively, the surgery group exhibited modest triceps weakness and mild numbness in the thumb, index, and middle fingers, which corresponded to the distribution of the C7 nerve following neurotomy. All adverse events were transient, resolving within 3 months. The absence of allograft rejection highlights ANA’s biological advantage, whereby chemical decellularization eliminates immunogenic components while retaining the native extracellular matrix to preclude immune reactions and provide a scaffold for Schwann cell migration and axonal growth. Our prior works demonstrated ANA’s nerve regenerative efficacy in primate nerve defect models [23, 24], confirmed safety and efficacy in CC7 transfer for brachial plexus injury in a retrospective clinical trial with 4-year follow-up [9], and exhibited satisfactory outcomes for 1–5 cm nerve defects in a prospective trial [7], which collectively support its suitability for our 3-cm application in the current study.

The average allograft length in the surgery group was 36.94 ± 4.49 mm, with the separable C7 nerve root averaging 54.28 ± 2.94 mm. This is insufficient for direct tension-free anastomosis in CC7 transfer, unless additional length is obtained via distal dissection of the C7 anterior and posterior divisions. Excessive distal dissection, however, increases surgical complexity and risks damaging nerve fibers from upper and lower trunks in the anterior and posterior cords, potentially causing irreversible donor-side brachial plexus injury. Our study achieved FMA improvements comparable to prior multicenter reports of a 15.14-point increase with autologous grafts or direct neurorrhaphy in CC7 transfer [5]. Notably, we addressed clinical limitations of the procedure, as ANAs not only offset insufficient donor C7 nerve length but also eliminate donor-site morbidity. Combining CC7 transfer with ANA streamlines the surgical process, reducing operative time, minimizing surgical trauma (Table 3), and improving clinical safety and feasibility—thereby highlighting the study’s innovative value in resolving unmet needs in nerve reconstruction for CC7 transfer.

Table 3.

Surgical status in Surgery Group (N =17)

Surgical status
Time of operation (h)	3.64 ± 0.39
Length of donor C7 nerve root (mm)	54.18 ± 2.94
Allograft Length (mm)	36.94 ± 4.49
Length of surgical incision (cm) Left Right	6.41 ± 0.51 6.35 ± 0.61

The main limitation of this study is its non-randomized observational design. Although all patients were enrolled according to unified criteria, group assignment relied on patients’ subjective preferences. Patients declining surgery primarily had concerns about surgical risks stemming from insufficient procedure understanding. To reduce confounding factors related to postoperative rehabilitation, both groups received rehabilitation therapy at the same center with identical protocols with consistent frequency and programs. Nevertheless, a certain degree of individualization still existed in rehabilitation practice. Additionally, we lacked dedicated control groups for autologous nerve grafting and direct nerve anastomosis. Although adding such cohorts would have strengthened the study’s credibility, recruiting adequate patients for these arms proved challenging due to clinical practicalities, patient preferences, and ethical considerations. The small sample size further limited our ability to accurately describe the characteristics of outcome changes in the following year. In response to this limitation, we plan to conduct multicenter clinical studies with longer follow-up periods and larger sample sizes in the future.

Conclusions

Our findings suggest that combining CC7 nerve transfer with ANA may offer a preliminarily therapeutic option for chronic spastic upper limb dysfunction following unilateral cerebral injury. This approach represents a feasible option characterized by manageable surgical complexity and minimal postoperative complications, particularly for selected patients meeting specific clinical criteria.

Abbreviations

CC7 nerve

Contralateral cervical seventh nerve

ANA

Acellular nerve allograft

FMA

Fugl-Meyer assessment

MAS

Modified Ashworth Scale

ARAT

Action research arm test

Author contributions

Conception and design: HG.W, A.J. Acquisition of data: A.J, ZP.L. Analysis and interpretation of data: A.J, LW.Y. Drafting the article: A.J, LW.Y, ZP.L. Critically revising the article: A.J, LW.Y, ZP.L. Reviewed submitted version of manuscript: HG.W, LW.Y. Statistical analysis: A.J, JT.F, JY.F. Administrative/technical/material support: CY.Z, JL.D, T.Z, BG.Q, CB.Z. Study supervision: HG.W, QT.Z.

Funding

This work was supported by the National Key Research and Development Plan of China (Grant No. 2022YFC2602801). the National Natural Science Foundation of China (Grant No. 82101437), the Guangdong Basic and Applied Basic Research Foundation (Grant Nos. 2022A1515012072 and 2024A1515013183), Guangzhou Municipal Science and Technology Project (Grant No. 202201010775), the Guangzhou Science and Technology Plan Project (Grant No. 2023A04J2234), and Featured Clinical Technique of Guangzhou (Grant No. C3230111).

Data availability

The raw de-identified data supporting the findings of this study are available from the corresponding author(s) upon reasonable request.

Declarations

Ethics approval and consent to participate

Ethics approval for the collection of demographics, and clinical and treatment data of all participants was obtained from the First Affiliated Hospital of Sun Yat-sen University institutional review boards (ID: [2020] 440). This study was conducted in strict accordance with the principles outlined in the Declaration of Helsinki. Written informed consent was obtained from all enrolled registry participants.

Consent for publication

Written consent for publication has been obtained from all participants involved in Supplementary Videos.

Competing interests

The authors declare no competing interests.