Functional and Neuroplastic Effects of Cross-Education in Anterior Cruciate Ligament Rehabilitation: A Scoping Review with Bibliometric Analysis

Featured Application

As a low-cost and simple strategy, cross-education can be incorporated early in anterior cruciate ligament rehabilitation to maintain musculoskeletal strength, reduce pain and interlimb asymmetries, and improve dynamic stability.

Abstract

Anterior cruciate ligament reconstruction (ACLR) results in prolonged muscle weakness, impaired neuromuscular control, and delayed return to sport. Cross-education (CE), unilateral training of the uninjured limb, has been proposed as an adjunct therapy to promote bilateral adaptations. This scoping review evaluated the functional and neuroplastic effects of CE rehabilitation post-ACLR. Following PRISMA-ScR and JBI guidelines, PubMed, Scopus, Web of Science, and PEDro were searched up to February 2025. A bibliometric analysis was also conducted to report keyword co-occurrence and identify trends in this line of research. Of 333 screened references, 14 studies (price index: 43% and low-to-moderate risk of bias) involving 721 participants (aged 17–45 years) met inclusion criteria. CE protocols (6–12 weeks; 2–5 sessions/week) incorporating isometric, concentric, and eccentric exercises demonstrated strength gains (10–31%) and strength preservation, alongside improved limb symmetry (5–14%) and dynamic balance (7–18%). There is growing interest in neuroplasticity and corticospinal excitability, although neuroplastic changes were assessed heterogeneously across studies. Findings support CE as a feasible and low-cost strategy to complement early-stage ACLR rehabilitation, especially when direct loading of the affected limb is limited. Standardized protocols for clinical intervention and neurophysiological assessment are needed.

1. Introduction

The anterior cruciate ligament (ACL) is one of the key ligaments that stabilize the knee, connecting the femur to the tibia and controlling rotation during flexion and extension [1]. ACL injuries, which manifest as stretching or tearing, are common in sports involving rapid movements, changes in direction, jumps, landings, and indirect or direct trauma to the knee, such as in soccer, basketball, and American football [2,3,4,5,6]. It has been estimated that the incidence of isolated ACL injuries is approximately 68.6 per 100,000 people per year, but it can reach figures close to 227 per 100,000 in young populations [7,8]. Among athletes, these numbers are usually higher but vary depending on age, sex, sport, type of exposure, and level of participation [9,10,11,12]. In addition to the functional impact, these injuries entail considerable economic costs, with an estimated USD 17,000 per anterior cruciate ligament reconstruction (ACLR) procedure [13]. In the context of professional sports, particularly in Europe, the incidence of ACL rupture is also significant among elite players, who often return to competition after surgery in relatively short periods, though these vary between leagues. For example, the average time to return to competition after surgery has been reported as 193 days in the French league, while in the English Premier League, it extends to 321 days. In contrast, the Italian, French, and German leagues show a faster recovery compared to the English league [14].

ACLR is considered a fundamental intervention to facilitate a return to sports activity [7,8,12,15]. However, after undergoing ACLR, it is common to observe decreased muscle strength, loss of knee stability, and high pain perception, which can delay the return to sport [16]. In fact, impaired muscle control often persists for up to two years after surgery [17,18]. Therefore, implementing an efficient rehabilitation process is crucial to reducing the risks associated with ACLR and improving functional outcomes [19,20]. These limitations have been documented in a recent systematic review, which shows that return-to-sport rates after ACL reconstruction can be as low as 24% [19]. Supporting the shortcomings of traditional rehabilitation approaches, these may be associated with incomplete recovery of muscle strength and neuromuscular control deficits (imbalance between flexors and extensors of the knee) [21,22], delaying the recovery process and increasing the risk of graft reinjury, additional injuries, and osteoarticular pathologies [20,23].

In this context, one of the proposed methods to optimize conventional rehabilitation is training the muscles of the uninjured limb, a technique known as cross-education (CE) [24]. First described in 1894, cross-education (CE) refers to the phenomenon whereby unilateral strength training induces bilateral neuromuscular adaptations [25]. Recently, CE has gained attention for its potential to preserve strength and promote recovery in various rehabilitation settings [26].

Regarding ACL rehabilitation, CE has demonstrated improvements in strength, kinesthesia, and balance in as little as four weeks, which is relevant since musculoskeletal injuries are associated not only with strength deficits but also with changes in the motor cortex and other brain regions [27,28]. It is important to note that CE can be implemented through various training modalities, including both isometric and dynamic exercises [29,30]. In ACLR, it is essential to address not only peripheral changes but also central nervous system alterations. Neuroplasticity, the brain’s ability to reorganize in response to external stimuli or structural injuries, plays a key role in this process [31]. In this scenario, CE has shown positive effects by inducing adaptations in the untrained limb through central mechanisms linked to neuroplasticity [32].

Despite the demonstrated therapeutic potential of CE in ACL rehabilitation, significant gaps remain in understanding its neuroplastic mechanisms and their impact on the functional recovery of the untrained contralateral limb. Although CE has shown relevant potential for transferring functional improvements, the associated neuroplastic mechanisms are not yet clearly defined. Indeed, while there is consensus on the efficacy of CE, standardized protocols or application guidelines for ACL rehabilitation have yet to be established [33].

This lack of understanding, along with the absence of standardization, hinders the effective integration of CE into rehabilitation protocols, limiting the optimization of functional recovery and neurological adaptation [25,33,34,35,36]. Addressing these gaps through critical evaluation of measurement tools could contribute to shortening rehabilitation times, reducing reinjury risk, and prevent persistent functional deficits, thereby facilitating a safer and more effective return to physical and sports activities. The aim of this scoping review was to examine the available scientific evidence on the functional and neuroplastic effects of CE during ACL rehabilitation.

2. Materials and Methods

2.1. Protocol Registration

Given the conceptual diversity and methodological variability observed in CE protocols and outcome measures, a scoping review design was chosen over a traditional systematic review to better map the current evidence and identify knowledge gaps relevant to ACLR. For the development of this scoping review, we implemented the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Scoping Reviews (PRISMA-ScR) [37]. In accordance with Joanna Briggs Institute (JBI) guidelines for scoping reviews [38], we optimized the core methodology throughout the key stages (from problem formulation and literature search to evaluation, analysis, and presentation of findings) to systematize the review process and strengthen scientific rigor [39]. The protocol for this scoping review has been published on Figshare to make it publicly accessible and avoid unnecessary duplication of analysis for the same study objective (doi: 10.6084/m9.figshare.24268927).

2.2. Eligibility Criteria

The inclusion criteria for this scoping review were as follows: (i) experimental, observational, or theoretical articles, including randomized controlled trials, longitudinal studies, case studies, integrative reviews, systematic reviews, and meta-analyses; primary studies had a minimum follow-up period of six weeks, and secondary studies complied with PRISMA or COCHRANE guidelines or were registered in PROSPERO; (ii) peer-reviewed articles published up to the current date; (iii) publications written in English or Spanish; (iv) full-text availability; and, (v) articles reporting on the effects of anterior cruciate ligament rehabilitation through unilateral training or CE. Studies were excluded if they (i) were not original research (e.g., Editorials, commentaries, notes, theses), (ii) lacked a full-text version, (iii) involved participants with comorbid conditions unrelated to ACL injury, (iv) used combined interventions without isolating CE effects, or (v) presented unclear methodology.

2.3. Information Sources

PubMed, Scopus, Web of Science, and PEDro were selected to examine the available literature. Additionally, further articles were manually searched in Google Scholar or through snowballing.

2.4. Search Strategy

Based on the Population–Concept–Context (PCC) framework, the research question guiding this review was: What are the functional and neuroplastic effects of CE-based rehabilitation in individuals with ACL injury [38]? Database searches were conducted using specific algorithms: PubMed and Scopus: “Anterior cruciate ligament” OR “anterior cruciate ligament reconstruction” AND “cross-education” OR “cross exercise” OR “ unilateral strength training” OR “cross training” OR “cross transfer” OR “strength transfer” OR “contralateral strength training”; Web of Science: (“Anterior cruciate ligament” OR “anterior cruciate ligament reconstruction”) AND (“cross-education” OR “ unilateral strength training” OR “cross training” OR “cross transfer” OR “strength transfer” OR “contralateral strength training”); and PEDro: 1. “Anterior cruciate ligament”; 2. Anterior cruciate ligament AND cross-education; 3. Anterior cruciate ligament AND contralateral strength training. The database search was conducted between December 2024 and February 2025.

2.5. Selection and Data Collection Process

Two of the authors (J.D.Q. and J.D.A.) conducted independent searches in the selected databases. Publications that met the inclusion criteria were selected to proceed with the analysis and synthesis phases. A table was designed to report the results and compare key findings, including study type, design, objectives, intervention, procedures, and their main findings. Discrepancies will be identified and resolved through discussion with other authors if necessary (J.M.V., A.R-J., and D.A.B.). Based on best practices and previous studies by the DBSS Research Division [40,41], we assessed the obsolescence of the literature by calculating Price’s index, defined as the ratio of references published within the past five years to the total number of references. The study selection was carried out during the months of February and April 2025.

2.6. Risk of Bias Assessment

The risk of bias was assessed according to the type of studies, based on the critical appraisal tools for evidence synthesis from JBI available on their website (https://jbi.global/critical-appraisal-tools, accessed on 5 February and 1 March 2025), and then graphically illustrated using Cochrane’s RevMan 5.4 software.

2.7. Bibliometric Analysis

Trends in the field of CE were examined using VOSviewer v1.6.19 software to conduct bibliometric visualization. The first step involved performing a search in the Scopus database using the keyword: “cross-education” OR “cross education.” Subsequently, an overlay map based on the co-occurrence of authors’ keywords over the last 5 years was created to identify potential trends in this line of research. Minimum requirements for reporting bibliometric reviews of biomedical literature were considered [42].

3. Results

3.1. Study Selection

After running the search algorithms with Boolean operators (filtered by date and language), 333 references were retrieved. After removing duplicates from the publications, 219 studies remained. However, upon evaluating the titles and abstracts, only 28 potentially eligible publications were selected, of which 14 were subsequently excluded based on our pre-established criteria, resulting in a total of 14 studies that met the predefined requirements, with a price index of 43% [17,18,23,24,43,44,45,46,47,48,49,50,51,52]. Figure 1 shows a flow diagram of the literature search.

3.2. Risk of Bias Within Studies

The methodological quality of the selected clinical trials is presented in Figure 2, while the risk of bias of the selected systematic review is presented in Figure 3.

The methodological quality of the selected case study is presented in Figure 4.

3.3. Results of Individual Studies

The main characteristics and results of the selected studies are shown in

Table 1. Synthesis of the selected articles.

Type of Study	Design	Objectives	Intervention	Outcomes	Key Findings/Conclusions	References
RCT	8 weeks, 48 post-ACLR patients (29.5 [6.8] years), n = 16/group (concentric CE, eccentric CE, CON); physically active	Evaluate effects of concentric and eccentric isokinetic contralateral limb training on QF recovery post-ACLR.	MVIC (IsoMed2000), SLHD, IKDC, Tegner. Unilateral isokinetic training (knee extension), 3 times/week, 3 × 12 reps at 60°/s, ROM 10–90°, concentric or eccentric mode.	MVIC (IsoMed2000), SLHD, IKDC	↑ QF in CE groups vs. CON at week 12 (p = 0.04/0.03) and week 24 (p = 0.01/<0.001); concentric: +28%, eccentric: +31%; no differences in SLHD or IKDC.	Harput et al. (2019) [17]
RCT	26 weeks, 43 post-ACLR (EXP = 22, CON = 21; 24 males/19 females), 28 [9] years; physically active (Tegner 7–8); no prior strength training data	Evaluate if adding CE to standard post-ACLR rehabilitation improves subjective knee function and strength recovery through week 26.	EXP group performed unilateral leg press and extension (contralateral CEE), 2 times/week, 3 × 8–12RM, weeks 1–12. Both groups received standard rehabilitation.	KOOS, MVIC (Biodex), HOP, LSI, Tegner	No CE effects on KOOS, QF, HMF or HOP vs. CON. Both groups improved KOOS (−15%), QF (↑5–14%), HMF (↑7–18%) by week 26.	Tjerk Zult et al. (2018) [18]
RCT	8 weeks CE, assessed at 10 and 24 weeks, 44 post-ACLR (CE = 22, CON = 22; 25 males/19 females), 31.8 ± 9.7 years; recreational athletes	Investigate immediate (10 wk) and long-term (24 wk) effects of high-intensity CE on strength and function post-ACLR.	CE with knee extension, hamstring curl, and leg press (contralateral limb), 3 times/week, 3 × 3–5RM, 1.5–2 min rest; initiated 2 weeks post-op; CON: stretching	QF, HMF, RFD (custom dynamometer), HOP, IKDC	At 10 weeks: ↓QF operated limb CE = −16.6% vs. CON = −32% (p = 0.004); ↑QF non-operated limb (7% vs. −7%, p < 0.001). No HMF or HOP differences. Similar LSI between groups (QF = 0.86).	Minshull et al. (2021) [23]
RCT	26 weeks, 43 post-ACLR (EXP = 22, CON = 21; 24 males/19 females), 28 [9] years; recreational athletes	Examine whether adding CE to standard rehabilitation improves neuromuscular recovery post-ACLR.	EXP: unilateral leg press and extension (contralateral CEE), 2 times/week, 3 × 8–12RM, weeks 1–12; both groups received standard rehab. From weeks 24–36: power/agility training with unilateral jumps and direction changes.	MVIC (Biodex), CAR (IT), QF, HMF, HOP, SLS, SEBT, joint proprioception, Tegner	CE showed no strength/function benefits vs. CON. At week 12, CE ↓ CAR by 6% (p = 0.023) and impaired LSI by 9–10% (p < 0.05). Both groups improved force control (↑13–56%) and dynamic balance (~7%).	Tjerk Zult et al. (2019) [49]
SR and MA	7 RCTs included (5 in meta-analysis), 177 post-ACLR patients, 27.98 [2.23] years	Determine effectiveness of uninjured limb unilateral training on muscle strength and knee function post-ACLR.	Unilateral training of healthy limb. Isometric/isotonic/isokinetic strength, 2–5 times/week, 8–26 weeks vs. standard rehab.	MVIC (30–65°), LSI (Q), IKDC, LSI (SHT), self-reported questionnaires	CE improved QF MVIC (SMD = 0.60 to 0.58, p < 0.01); ↑ QF LSI (MD = 0.06, p = 0.01); no effect on HMF LSI (MD = −0.02, p = 0.48).	Iván Cuyúl-Vásquez et al. (2022) [24]
Clinical trial	8 weeks, 30 athletes with ACLR (EXP = 15, CON = 15; no sex data), 18–40 years	Investigate CE program effects on muscle activation and movement control in ACLR athletes (≥6 months post-op).	EXP: 3 times/week unilateral strength training (healthy leg) for TA, gas, RF, VM, BF, GM, RA, ES. CON: no structured exercise.	sEMG synchronized with force plate. GRF and COP oscillation analysis, MVIC	↑ EMG activation in TA, RF, GM during swing; ↑ TA, VM, RF, BF, GM during stance (p < 0.05). ↓ vertical/posterior GRF, ↓ lateral/anterior COP (p < 0.05).	Mostafa Payandeh & Daneshmandi (2025) [43]
RCT	6 weeks, 40 post-ACLR (EXP = 20, CON = 20; 22 males/18 females), 33.7 [5.6] years; no strength training data	Assess CE effects on knee function, kinematic parameters, dynamic balance, and plantar pressure post-ACLR.	EXP: CE (healthy limb) + conventional rehab, 3 times/week, progressing unilateral balance/functional tasks. CON: conventional rehab only.	SLS, ROM (goniometer), sEMG (Noraxon), HOP, GRF/COP (Zebris), Lysholm	EXP outperformed CON in Lysholm, ROM, RF activation, step length, ML control, forefoot/rearfoot pressure (p < 0.05); no midfoot/velocity differences.	Liu et al. (2025) [51]
RCT	8 weeks, 88 post-ACLR (EXP = 44, CON = 44; 59 males/29 females), 28–29 years, active ≥3x/week	Compare unilateral vs. bilateral isotonic exercises for functional/strength symmetry post-ACLR with contralateral BPTB graft.	EXP: unilateral strength (donor leg) 2 times/week, 3 × 12 reps (press, terminal extension, leg ext., SLR, lunge). CON: bilateral equivalent.	MVIC (Biodex, 60°/s), H:Q, ROM (goniometer), laxity (KT-1000), HOP, Lysholm	EXP showed ↑ interlimb symmetry in peak torque, H:Q, HOP (p < 0.001). Greater donor-leg gains. CON improved reconstructed leg more.	Marcio Oliveira et al. (2022) [45]
RCT	8 weeks, 30 male athletes post-ACLR (EXP = 15, CON = 15), 27.5 [4.6] years; no strength training data	Evaluate contralateral neuromuscular exercises on static/dynamic balance, knee function, and pain post-ACLR.	EXP: CE 4 times/week, 30 min/session (unilateral balance on stable/unstable surfaces with arm tasks). CON: conventional PT.	SEBT, BESS, Stork test, Lysholm	EXP improved SEBT (ant/post/med/lat; p < 0.05), BESS (4 stances; p < 0.05), Stork (p = 0.044), ↓ VAS (p = 0.014). No Lysholm changes (p = 0.71).	Motahareh Karimijashni et al. (2023) [48]
Case Study	8 weeks, 5 post-ACLR (3 males/2 females), 16–21 years	Describe eccentric CE effects on neuroplasticity/perceived outcomes post-ACLR.	24 sessions (3 times/week), 4 × 10 eccentric isokinetic contractions at 60°/s (0–90° ROM) in healthy leg (≥60% 1RM); ACLR-free.	fMRI (brain activation), H-reflex (SRE), TMS (CSE), KOOS, TSK, IKDC, Tegner, qualitative interviews	↑ spinal (H:M ratio +57%) and cortical excitability (MEP +235%); ↓ frontal activity (fMRI); ↑ KOOS QOL (163%), ADL (136%), Sport (3076%).	Lepley et al. (2018) [44]
RCT	8 weeks, 42 soldiers post-ACLR (3 groups: 14 each; males only), 20–25 years; no strength training data	Compare 3 vs. 5 days/week CEE effects on CLL deficit post-ACLR.	CEE (healthy leg ext.) at 3x/week (G1) or 5 times/week (G2); 5 × 6 reps at 80% 1RM, 2 min rest. CON: standard rehab.	Isometric MVIC (KinCom AT+) at 60°; QF and QD pre/post.	CLL deficit post-CEE: G1 = 27.95%, G2 = 29.82%, CON = 53% (p < 0.05); G1/G2 ↑ healthy-leg CLL (22.7%/18%), ↓ injured-leg CLL (16.25%/6.3%).	Papandreou et al. (2013) [47]
RCT	8 weeks, 42 soldiers post-ACLR (CE 3x/week = 14, CE 5x/week = 14, CON = 14; males only), 20–25	Investigate CEE (3 vs. 5 days/week) effects on ART and Lysholm early post-ACLR.	CEE (unilateral leg ext.) at 3 or 5 days/week, 5 × 6 reps at 80% 1RM; all groups received conventional rehab.	Isometric MVIC (KinCom AT+), ART at 45°/60°/90°, Lysholm	CE 3 times/week improved ART at 90° vs. CON (p = 0.01); no differences at 45°/60°. Lysholm ↑ in CE 3 times/week (Δ+7.5, p < 0.01) and CE 5 times/week (Δ+3.78, p = 0.03) vs. CON.	Papandreou et al. (2009) [46]
RCT	8 weeks, 42 soldiers post-ACLR (CE 3x/week = 14, CE 5x/week = 14, CON = 14; males only), 20–25 years	Assess CEE effects on isometric QF at 45°/90° early post-ACLR, comparing 3 vs. 5 days/week.	CEE (healthy-leg unilateral ext.) at 3 or 5 times/week, 5 × 6 reps at 80% 1RM. Both groups received standard rehab.	Isometric MVIC (KinCom AT+) at 45°/90°	CE 3 times/week showed ↑ QF vs. CON at 45° (Δ98.4 Nm, p = 0.02) and 90° (Δ119.8 Nm, p < 0.01); no differences between CE groups.	Papandreou et al. (2007) [50]
RCT	10 weeks (6 weeks conventional rehab + 4 weeks intervention), 46 post-ACLR (EXP = 26, CON = 20), 30.9 [9.3] years	Determine if added isokinetic training improves knee strength/function post-arthroscopic ACLR.	EXP: 2 times/week, 3 × 20 reps at 180°/s (concentric), operated leg. H:Q torque. Both groups completed the initial 6-week conventional rehab.	MVIC (Biodex 3), ROM (Biodex), VAS, Lysholm, time-to-peak torque, torque variance, H:Q	EXP ↑ extension/flexion torque (30°/60°), ↓ extension torque variance, ↓ H:Q (30°); ↑ flexion ROM (Δ32°, p = 0.026), ↑ extension ROM (Δ−4.58°, p = 0.044); no Lysholm/VAS differences	Cheng-Pu Hsieh et al., (2016) [52]

ACL = Anterior Cruciate Ligament; ACLR = Anterior Cruciate Ligament Reconstruction; ART = Accelerated Reaction Time; BESS = Balance Error Scoring System; BF = Biceps Femoris; CAR = Central Activation Ratio; CE = Cross-Education; CEE = Contralateral Eccentric Exercise; CON = Control Group; CLL = Contralateral Limb Strength; CSE = Corticospinal Excitability; ES = Erector Spinae; EXP = Experimental Group; Gas = Gastrocnemius; GM = Gluteus Medius; H:Q = Hamstring-to-Quadriceps Ratio; HMF = Hamstring Maximal Force; HOP = Hop for Distance; IKDC = International Knee Documentation Committee; KOOS = Knee Injury and Osteoarthritis Outcome Score; LSI = Limb Symmetry Index ([Operated Limb Strength / Non-Operated Limb Strength] × 100); Lysholm = Lysholm Score; MVIC = Maximal Voluntary Isometric Contraction; QF = Quadriceps Strength; RA = Rectus Abdominis; RF = Rectus Femoris; RCT = Randomized Clinical Trial; RFD = Rate of Force Development; ROM = Range of Motion; SEBT = Star Excursion Balance Test; SLHD = Single Leg Hop for Distance Test; SLS = Single Leg Stance Test; SR&MA = Systematic Review and Meta-Analysis; SRE = Spinal Reflex Excitability; sEMG = Surface Electromyography; TA = Tibialis Anterior; Tegner = Tegner Activity Scale; TMS = Transcranial Magnetic Stimulation; TSK = Tampa Scale for Kinesiophobia; VAS = Visual Analog Scale; ↑ = increase; ↓ = decrease.

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Twelve randomized controlled clinical trials (RCTs), one case study, and one systematic review with meta-analysis were included, totaling 721 participants, reduced to 637 after removing duplicates of participant samples across different studies by the same author. The sample primarily consisted of young adults, aged between 17 and 45, with a BMI of 21 to 25. The interventions lasted between 6 and 12 weeks, with 2 to 5 sessions per week, focusing on unilateral training of the contralateral non-injured leg. The protocols included isometric and dynamic exercises with progressive loads [24,46,47,50], and some studies used electromyography (EMG) to monitor neuromuscular activation and physiological adaptations [43,51]. A low-to-moderate risk of bias was detected across the articles.

The studies employed various assessment tools, such as isokinetic dynamometry, stability and balance tests, and pain perception scales. Muscle strength, range of motion (ROM), and knee function were also evaluated. The results showed significant improvements in strength and function of the untrained contralateral limb, particularly in quadriceps strength and functional symmetry. Additionally, a gradual recovery of strength was observed in the operated leg, along with improvements in functionality and dynamic balance. However, the variability in results highlights the need to standardize protocols and measurement tools to optimize the clinical application of CE in ACL rehabilitation.

Regarding neuroplasticity, only one study [44] directly evaluated central adaptations using neurophysiological tools such as fMRI, TMS, and H-reflexes, reporting significant increases in cortical and spinal excitability following eccentric CE. Additionally, other studies indirectly addressed neuroplasticity through changes in EMG activity, postural control, and motor coordination [43,51], suggesting functional improvements potentially mediated by central nervous system adaptations.

3.4. Bibliometric Analysis

A bibliometric analysis of keyword co-occurrence in articles on CE was conducted, using VOSviewer to outline the state of the art in this emerging field. This approach allows for the identification of trends, conceptual relationships, and knowledge gaps, facilitating an understanding of how CE is researched and applied in neuromuscular training and rehabilitation. In the resulting map, each node represents an author keyword, where the size reflects its co-occurrence frequency, the thickness of the links indicates the strength of the relationships, and the color denotes conceptual clustering (Figure 5).

The results highlight the prominence of CE (149:226) in the literature, particularly in relation to resistance training (57:112) and rehabilitation (30:63), supporting its use for improving strength through unilateral training. The strong association with strength (46:86) and interlimb transfer (19:48) underscores its relevance in the functional recovery from injuries, including those of the anterior cruciate ligament (5:7). Additionally, the growing interest in terms such as neuroplasticity (7:23) and corticospinal excitability (8:20) demonstrates that CE not only enhances strength but also induces beneficial neurological changes for recovery. Although the application of EC in clinical contexts, such as stroke rehabilitation (4:6), is expanding, areas like mirror therapy (5:9) and assessment through motor-evoked potentials (4:9) remain less explored, opening new opportunities to optimize its implementation using neuromuscular activity quantification methods, such as electromyography (22:50) and H-reflex (6:15). These findings not only reinforce the potential applicability of CE in post-surgical rehabilitation and muscle function improvement but also establish a foundation for future research integrating clinical and neurophysiological approaches, which could contribute to the standardization of CE rehabilitation protocols.

4. Discussion

This scoping review aimed to synthesize the scientific evidence on the functional and neuroplastic effects of cross-education (CE) interventions during the rehabilitation after anterior cruciate ligament reconstruction (ACLR). Overall, the results show that CE can play a complementary role in postoperative recovery after ACLR, particularly in the early phases of rehabilitation when direct loading on the affected limb must be limited. Most of the selected studies were randomized controlled trials [17,18,23,45,46,47,48,50,51], along with one quasi-experimental study [43], a case study [44] and a systematic review with meta-analysis [24]. These investigations were primarily conducted in young, physically active adults undergoing different ACLR surgical techniques. Generally, the interventions focused on unilateral training of the contralateral limb to assess its influence on muscle strength, balance, functional performance, and neuromuscular activation.

Notably, several clinical trials repeatedly reported that CE in ACLR helps preserve or improve quadriceps strength in the affected limb, especially during early postoperative rehabilitation. This finding was observed between weeks 8 and 26 post-surgery in some studies [17,46,47,48,49,51]. These interventions involved moderate-to-high-intensity eccentric or isometric contractions. Similarly, improvements were seen in functional parameters such as limb symmetry, dynamic balance, and postural control, reinforcing CE’s potential clinical value as an adjunct tool in neuromuscular recovery. Conversely, discrepancies were noted between studies, particularly those using less intensive protocols or featuring delayed CE implementation. For example, two controlled trials by Zult et al. [49] found no significant effects of CE on neuromuscular function or functional recovery compared to conventional rehabilitation, suggesting that outcomes may largely depend on implementation timing, contraction type, and stimulus intensity, as per the available literature.

To evaluate these effects, studies employed a variety of objective and subjective tools. Objective measures included isokinetic dynamometry, surface electromyography, and functional tests such as the Single-Leg Hop Test, Star Excursion Balance Test, and Balance Error Scoring System. Subjective measures included knee function scales like the International Knee Documentation Committee (IKDC) [53], the Knee Injury and Osteoarthritis Outcome Score (KOOS) [54], the Lysholm Knee Scoring Scale (Lysholm) [54], and the Hughston Clinic Knee Scoring System (HCKS) [55]. Additionally, some studies, particularly those conducted in non-ACL contexts, used advanced neurophysiological techniques such as TMS, fMRI, or transcranial direct current stimulation to investigate potential cortical reorganization mechanisms associated with CE.

From a functional perspective, most of the included studies reported significant improvements in quadriceps strength of the operated limb, limb symmetry, hamstring-to-quadriceps (H:Q) ratio, postural control, and performance in various functional tests. These adaptations were particularly evident between weeks 8 and 26 after surgery. Interventions incorporating high-intensity eccentric or isometric contractions of the contralateral limb were effective in attenuating muscle strength deficits [46,48]. For example, Harput et al. [17] demonstrated that high-intensity eccentric CE produced greater quadriceps strength gains (+31%) compared to concentric CE or conventional rehabilitation. Conversely, Zult et al. [18] found no significant improvements when CE was performed with lower intensity or delayed in the postoperative timeline, highlighting that both the load magnitude and timing of implementation are key determinants of clinical outcomes.

Regarding neuroplastic effects, direct evidence in ACLR populations is scarce. Only the case series by Lepley et al. [44] employed a CE-based intervention and their study provided relevant data by analyzing the relationship between quadriceps motor unit properties and corticospinal excitability in ACLR patients. Their results showed that lower discharge rates and poor motor unit recruitment were associated with reduced excitability in the primary motor cortex. These findings support the idea that postoperative functional deficits may be mediated not only by peripheral factors but also by central mechanisms, which could be modulated through strategies like CE. Nevertheless, most studies in this area come from research on healthy individuals or those with different neurological conditions, such as stroke or unilateral immobilization. These studies provide additional evidence on potential neurophysiological mechanisms of CE, including increased primary motor cortex excitability, reduced intracortical inhibition, and functional changes in interhemispheric connectivity [56,57,58].

Collectively, the findings of this scoping review support the potential of CE as a complementary tool in designing postoperative ACL rehabilitation programs, particularly in early phases where direct training of the affected limb is limited. The possibility of preserving or even improving muscle strength and functional performance through stimuli applied to the non-injured limb could help reduce inactivity time, mitigate neuromuscular asymmetries, and optimize readiness for progressive return to loading. From a clinical standpoint, these results position CE as a viable option within individualized rehabilitation protocols, especially in contexts where careful load progression is needed.

Similarly, the identified methodological limitations, along with the scarce evidence on neuroplasticity in ACLR populations, underscore the need for future research incorporating direct neurophysiological techniques. Standardizing intervention protocols and assessing CE effects at different postoperative stages would be beneficial. Additionally, expanding the study population to include women, less physically active individuals, and patients with different graft types would improve the clinical applicability of findings. Exploring the long-term impact of CE, as well as its combination with other therapeutic modalities, could represent a promising research avenue in rehabilitation.

4.1. Limitations and Future Directions

While this scoping review highlights clinically valuable insights, several limitations inherent to the available evidence must be acknowledged. First, several studies featured small sample sizes (n < 30), limiting statistical power and generalizability. Significant heterogeneity exists across included studies regarding sample characteristics (age, sex, graft type, physical activity level), intervention protocols (contraction types, duration, postoperative phase for CE initiation), and outcome measures (e.g., use of isokinetic vs. isotonic testing, different timepoints). This variability along with a relatively low price index (<50%) complicates direct comparisons and hinders standardized clinical recommendations. We advocate for an individualized, multisystem approach that considers prior knowledge and workload (external/internal loads), as these factors critically influence both injury prevention and management [40,59]. Second, despite observed functional improvements, direct evidence of CE’s neuroplastic effects in ACLR populations remains scarce. Only one study evaluated cortical structure and corticospinal excitability, leaving a key gap in understanding the neurophysiological mechanisms behind these adaptations. Most neuroplasticity data derive from healthy subjects or other neurological conditions, limiting generalizability. Further, inconsistent use of standardized measures for strength, neuromuscular activation, and knee function risks methodological bias and confounds result interpretation. Some trials also exhibited moderate bias due to unblinded designs or lack of active controls, potentially compromising internal validity.

Future research should prioritize the following:

• Advanced neurophysiological techniques (fMRI, TMS, evoked potentials) in real-world ACLR rehabilitation settings;
• Standardized CE protocols tested across rehabilitation phases, graft types, and fitness levels;
• Larger samples with greater inclusion of women and recreational athletes, plus longitudinal designs to assess long-term effects;
• Investigation of CE combined with adjunct therapies (e.g., neuromuscular stimulation [60], blood flow restriction [61,62], nutritional interventions [63,64]).

4.2. Practical Recommendations

This scoping review offers clinically relevant insights for post-surgical ACL reconstruction rehabilitation. CE emerges as a particularly safe, effective, and cost-efficient strategy during early rehabilitation when direct training of the affected limb is limited by pain, inflammation, or overtraining risks. Research demonstrates that single-limb strength training, particularly moderate-to-high intensity isometric or eccentric contralateral exercises, can improve quadriceps strength in the operated leg, reduce muscle atrophy, enhance limb symmetry, and support progressive return to exercise.

These interventions show benefits when applied 2–5 times weekly over 6–12 weeks, with functional improvements observable within eight weeks post-surgery. CE proves especially valuable in sports reconditioning programs where maintaining neuromuscular symmetry and minimizing downtime are critical for athletes. Importantly, these protocols can also benefit less active individuals when properly adapted to their functional capacity, injury type, and rehabilitation stage.

5. Conclusions

Rehabilitation protocols following ACL reconstruction (ACLR) should address more than just structural recovery, given the significant neurobiological changes accompanying the injury. These alterations lead to persistent muscle weakness, knee dysfunction, and maladaptive neuroplasticity. Cross-education (CE) has emerged as an effective intervention to counteract these maladaptive neuroplastic, functional, and morphological changes. The collective evidence analyzed in this scoping review supports the potential role of CE in preserving strength and improving functional outcomes during the early stages of ACLR rehabilitation. However, the limited use of neuroplastic assessment tools (e.g., fMRI, TMS, H-reflex) in current studies restricts our understanding of CE’s central adaptations. Future research should prioritize neuroimaging and other advanced techniques to clarify the neurobiological mechanisms of CE.