Arthrogenic muscle inhibition аfter anterior cruciate ligament rupture: a systematic review

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INTRODUCTION

Arthrogenic muscle inhibition (AMI) is a continuous reflex inhibition of the muscles surrounding the joint caused by an injury or a disorder [1]. This condition is characterized by the inability to voluntarily and fully activate the quadriceps femoris muscle, resulting in decreased muscle strength and function [2–4].

Jean-Martin Charcot, a French neurologist who coined the term “atrophic articular paralysis” in 1889, was the first to describe muscle weakness after a joint injury more than 130 years ago. Charcot noted paradoxical muscle weakness without any direct injury to muscle tissue or innervating nerves, laying the groundwork for understanding the reflex nature of this phenomenon.

In the 1960s and 1970s, electromyography techniques were introduced to assess muscle activation. The term “arthrogenic muscle inhibition” was proposed in the 1980s to describe a specific phenomenon of reflex inhibition of the muscles surrounding the affected joint. The modern understanding of AMI is primarily based on the research of Kennedy et al. [5], who were the first to use superimposed electrical stimulation to quantify central activation failure [6].

In 2000–2010, Hopkins [6], Pietrosimone [7], and other researchers introduced quantitative criteria for AMI and determined its prevalence after anterior cruciate ligament (ACL) injury. In 2010–2020, neuroplastic changes in the cortex and the role of supraspinal mechanisms in AMI were extensively investigated [8].

Modern research (from 2020 to the present) focuses on personalized treatment of AMI, its long-term complications, and the association with osteoarthritis [9, 10]. One of the first prospective studies of AMI progression found that the electromyographic activity of the quadriceps decreases by 50%–70% in the first hours after meniscectomy and can reach 80%–90% after 24 h [11]. These findings indicate that the acute phase of AMI is associated with the most severe neuromuscular disorders.

In the 2000s, Hopkins et al. [6] proposed the current definition of AMI, with a central activation ratio <95% indicating clinically significant muscle inhibition. The study found signs of AMI in 43% of patients after ACL injury, highlighting the relevance of AMI for sports medicine and orthopedic surgery [12, 13].

ACL reconstruction is one of the most common orthopedic surgeries, with up to 130,000 procedures performed annually in the United States alone [12, 14]. Despite advancements in surgery and rehabilitation, many patients experience persistent functional limitations, with only 55% able to return to their pre-operative activity level [12, 15]. AMI is one of the key factors that limit the efficacy of rehabilitation and increase the risk of recurrent injuries [9, 16].

AMI is reported in 30%–70% of patients after ACL injury, with bilateral damage in up to 25% of cases, making AMI a major health concern [6, 17]. Quadriceps activation failure is a chronic condition that can persist for months or years after surgery, with an incidence 12 months after ACL reconstruction reaching 12%–15% [18, 19]. Functional consequences in AMI include postural control impairment [20], decreased sports performance, and increased risk of post-traumatic osteoarthritis [17]. Resistance to conventional therapy is particularly concerning because standard exercise rehabilitation is frequently ineffective in severe AMI, necessitating specialty care [9, 20].

There are numerous gaps in our current understanding of AMI, including the lack of standard diagnosis protocols in real-world practice, low awareness of optimal intervention time and techniques, conflicting data on the efficacy of various therapeutic strategies, and uncertain prognostic factors and long-term outcomes [21, 22].

The review summarizes recent data on the underlying mechanisms, clinical manifestations, and therapeutic strategies in AMI after ACL reconstruction to provide evidence-based guidelines.

Search Methodology

A systematic review was conducted in accordance with PRISMA 2020 and the Cochrane Handbook.

A search was performed in PubMed/MEDLINE, Embase, CINAHL, Cochrane Library, Google Scholar, and Lens.org. Additionally, reference lists of the included publications were checked.

Inclusion criteria for the systematic review were as follows: study design (randomized controlled, controlled, and observational studies); studies with a main group of patients after ACL reconstruction (any therapeutic strategy) aged ≥18 years (adults) and a control group (placebo, standard of care, or no treatment); outcomes that included quadriceps activation, muscle strength, and functional parameters. Animal studies, case reports, and non-English language publications were excluded.

The following keywords and their combinations were used: arthrogenic muscle inhibition or AMI; anterior cruciate ligament or ACL; reconstruction or repair or surgery; quadriceps activation or muscle strength; rehabilitation or intervention; neuromuscular electrical stimulation or NMES.

Two co-authors with at least 10 years of experience screened the titles and abstracts, followed by a full-text screening of potentially relevant publications. Any disagreements were resolved by consulting the third reviewer.

The following data were extracted: study characteristics (design, sample size, duration of follow-up); participant characteristics (age, sex, time after surgery); intervention details; outcome measures; study findings.

The quality of randomized studies was assessed using Cochrane Risk of Bias 2.0 (RoB 2.0), and the quality of observational studies using the Newcastle–Ottawa Scale (NOS).

A qualitative synthesis by intervention type was performed, given the heterogeneity of interventions and outcomes.

After removing duplicates and performing primary screening for the full-text analysis, 156 of 1247 identified publications were selected. The final analysis included 67 eligible publications (Fig. 1).

 

Fig. 1. Study selection diagram (PRISMA diagram). ACL, anterior cruciate ligament; AMI, arthrogenic muscle inhibition.

 

These articles, published between 2000 and 2024, included 34 randomized controlled studies, 18 controlled clinical studies, and 15 observational studies. The total number of participants was 3847 (mean age: 28.4±6.7 years; 58% male).

NEUROPHYSIOLOGICAL MECHANISMS OF ARTHROGENIC MUSCLE INHIBITION

Spinal Mechanisms

According to research, AMI is caused by altered afferent input from the affected joint [23, 24]. The key mechanisms are gamma loop dysfunction and changes in spinal reflexes [25].

Konishi et al. [25] reported that ACL injury results in chronic gamma loop dysfunction, reducing the activation of high-threshold motor units. Studies using prolonged vibration found an aberrant response to vibration stimulation in patients with ACL rupture, indicating impaired afferent feedback [24].

Lepley et al. [26] reported bilateral reductions in spinal-reflexive excitability in patients after ACL reconstruction compared to controls. The quadriceps reflex was markedly reduced in both the operated and contralateral limbs.

Supraspinal Mechanisms

Grooms et al. [2] used functional magnetic resonance imaging to demonstrate considerable changes in brain activation in patients after ACL reconstruction, including increased activation in the contralateral motor cortex, lingual gyrus, and secondary somatosensory area, as well as diminished activation in the ipsilateral motor cortex and cerebellum [27]. Furthermore, an association has been found between decreased central activation and increased intracortical inhibition, confirming the role of supraspinal mechanisms in AMI [28]. Hopkins [6] and Lepley [29] found that ACL injury causes long-term neuroplastic changes. Moreover, increased activation of the pre-supplementary motor area and posterior temporal gyrus has been reported in patients with ACL injury, indicating a transition from automatic to voluntary motor control [30–32].

Fig. 2 shows an overview diagram of neurophysiological mechanisms in AMI.

 

Fig. 2. Pathogenesis of arthrogenic muscle inhibition. ACL, anterior cruciate ligament; CNS, central nervous system.

 

CLINICAL MANIFESTATIONS OF ARTHROGENIC MUSCLE INHIBITION

Not all patients with ACL injury develop AMI. According to various research, the incidence of AMI after ACL rupture ranges from 30% to 70% [1, 25]. Physicians must look for the signs of AMI in every patient because this condition does not necessarily occur in every ACL injury.

The main clinical signs of AMI are considerable difficulty or failure to voluntarily and fully activate the quadriceps during functional tests, such as straight leg raising or maximum knee extension [6]. Objective signs include decreased knee extensor strength observed during manual tests or measured using an isometric dynamometer [33].

Another common sign is severe muscle atrophy in the quadriceps group, especially the vastus medialis and rectus femoris [34]. Patients typically report persistent muscle weakness, a sense of “disconnection” between effort and actual muscle strength, and, in some cases, a delayed muscle response while walking and during active movements.

Functional limitations in AMI include difficulty maintaining balance when walking and running, gait disturbance, periodic joint instability, and a limited range of motion, primarily extension deficit [35]. Some patients develop chronic joint stiffness, fibrous nodules (cyclops lesions), pain, and a decrease in functional scores (KOOS, Lysholm, IKDC).

Additional signs of AMI include hypertonia or involvement of compensatory muscle groups, such as the popliteus muscle and gluteal muscles, resulting in complex movement asymmetries and delayed responses to external stimuli.

The primary triggers in AMI are severe joint effusion, pain, inflammation, and incorrect or excessive immobilization, which further reduces quadriceps activation and promotes functional defects [6].

AMI may affect both the operated and contralateral limbs, with considerable clinical consequences. Lepley et al. [26] reported bilateral reductions in spinal-reflexive excitability in patients after ACL reconstruction.

AMI is not only an acute symptom; it also worsens the long-term prognosis after ACL reconstruction, because the neurological response of the muscle impairs and delays rehabilitation, increasing the risk of recurrent injury and early osteoarthritis [17, 36]. According to research, AMI can persist for a long time after surgery [12]. Six months after ACL reconstruction, patients showed considerable quadriceps activation failure compared to controls [26]. Long-term follow-up findings indicate that reduced quadriceps strength in the operated limb may persist for up to 2–3 years after surgery.

DIAGNOSTIC TESTS IN ARTHROGENIC MUSCLE INHIBITION

The clinical diagnosis of AMI is based on the following: inability to fully contract the quadriceps under maximal volitional effort; visual quadriceps atrophy, especially the vastus medialis; knee extension strength reduced by more than 20% compared to the contralateral limb; impaired quadriceps activation during functional tests [6].

Electromyography

Electromyography (EMG) with superimposed electrical stimulation can facilitate objective quantitative assessment in AMI [25, 37, 38].

Neurophysiological changes on EMG in AMI include the following: decreased voluntary EMG amplitude of the quadriceps during maximum contraction; decreased motor unit recruitment and predominant loss of high-threshold motor units; increased muscle activation latency during rapid movements; asymmetrical activation compared to the contralateral side. The main quantitative parameter is the reduced central activation ratio (CAR), which is defined as a ratio between volitional muscle contraction and muscle activation elicited by an exogenous electrical stimulus during maximal volitional contraction. A controlled study by Hopkins et al. [6] found CAR of <95% in 43% of patients after ACL injury, which is indicative of AMI. This parameter correlated with functional outcomes and quadriceps strength.

Functional Tests

Instrumental tests. Isokinetic and isometric strength tests are performed using dynamometers such as Biodex, Con-Trex, Cybex, and Primus. Absolute peak quadriceps strength is measured at various contraction velocities (60 °/s, 180 °/s, 300 °/s) [33, 39]. A quadriceps strength reduction of >15% compared to the contralateral limb indicates AMI.

Clinical functional tests. The single-leg hop test requires the patient to do a standing long jump on the operated leg, landing on the same leg. The maximum hop distance is measured. The goal is to have no more than a 10% difference in hop distance between the injured limb and uninjured limb. In AMI, the reduction is 15%–25% [40].

Postural control assessment using inertial measurement units. Postural balance and sway path are assessed in impaired proprioception. Patients with AMI have a 20%–40% increase in sway area and a 30%–50% increase in sway path compared to normal values [20, 37, 41].

Neurophysiological Methods

Transcranial magnetic stimulation is used to measure corticospinal excitability [42–44]. This technique records motor evoked potentials of the quadriceps in response to magnetic stimulation of the motor cortex.

TREATMENT OF ARTHROGENIC MUSCLE INHIBITION

Therapeutic options in AMI include cryotherapy, neuromuscular electrical stimulation, structured exercise programs, biofeedback, transcranial magnetic stimulation, and vibrotherapy. A comprehensive approach that combines several interventions is considered the most effective [9, 45, 46].

Fig. 3 shows an overview diagram of therapeutic options in AMI.

 

Fig. 3. Diagnosis and treatment algorithm in arthrogenic muscle inhibition. ACL, anterior cruciate ligament; AMI, arthrogenic muscle inhibition; CAR, central activation ratio; EMG, electromyography; NMES, neuromuscular electrical stimulation.

 

Cryotherapy

Cryotherapy is the local use of low temperatures in the knee joint area to reduce pain impulses and reflex inhibition of the quadriceps [6].

Cryotherapy involves applying an ice pack or cold compression pad to the anterior surface of the knee joint for 20–30 min 3–4 times a day for the first 2–3 weeks after surgery. The required temperature is 10–15 °C. Contraindications: cutaneous sensory disorders, peripheral vascular diseases. Hopkins et al. [6] found that a 20-minute cryotherapy session considerably increases peak quadriceps strength and muscle fiber conduction velocity compared to controls. In a randomized controlled study by Loro et al. [47], there was a 38% increase in EMG activity of the vastus medialis and a 30% increase in maximum isometric knee extension strength after cryotherapy. A scoping review by Sonnery-Cottet et al. [9] found that cryotherapy is moderately effective in AMI.

Neuromuscular Electrical Stimulation

During neuromuscular electrical stimulation, electrical pulses influence motor neurons of the muscle to induce involuntary contractions, reducing AMI and restoring quadriceps strength [45, 48]. The duration of neuromuscular electrical stimulation is 4–6 weeks, 3–5 times per week, starting 3–7 days after surgery. The parameters are as follows: frequency, 50 Hz; pulse duration, 400–600 µs; and session duration, 20–30 min in the 1:2 on-off mode. The session ends when strength reduction is <20% and functional parameters are restored [45].

A systematic review by Kim et al. found that neuromuscular electrical stimulation combined with exercise therapy in the first 4 weeks after ACL reconstruction considerably improves quadriceps strength, as indicated by both short-term (≤6 weeks) and long-term (>6 weeks) follow-up. Early therapy (≤1 week after surgery) produces the best outcomes, with an effect size of 1.48 for quadriceps strength and gait parameters vs 0.44 in delayed treatment [45].

Exercise Programs

The recommended exercise program includes isometric contractions of the quadriceps, active knee range of motion, and proprioceptive exercises within the first 6 weeks after surgery to activate all components of the quadriceps [35, 49].

The exercise program must be the first-line therapy in AMI [11]. Early exercise therapy (≤1 week after surgery) is most effective [50].

Biofeedback

Biofeedback provides the patient with real-time data on physiological processes, facilitating informed control and improving muscle activation. This technique involves real-time visual (on a computer or manometer display) or audio (via loudspeakers) feedback on muscle amplitude and strength. Self-monitoring of these parameters facilitates motor relearning and improves muscle contraction [51].

Biofeedback using a manometer display for self-assessment of strength was more effective in early quadriceps activation than conventional exercises [52]. There was a considerable increase in amplitude and duration of motor unit action potentials. Christanell et al. [53] found that EMG biofeedback in the early phase of rehabilitation improved the range of knee extension and vastus medialis strength by 40%–60% compared to the control group.

Transcranial Magnetic Stimulation

Transcranial magnetic stimulation with short magnetic pulses and transcranial direct-current stimulation (tDCS) with weak current via scalp electrodes are noninvasive techniques for primary motor cortex neuromodulation that target the supraspinal mechanisms underlying quadriceps AMI [42, 54].

A 6-week course of anodal transcranial direct current stimulation combined with exercise therapy improves intracortical inhibition and excitability of the quadriceps in patients after ACL reconstruction [42]. Hopkins et al. [6] found that a single transcranial magnetic stimulation session improved AMI in 82% of participants for 60 min, with a CAR increase of ≥5 percentage points. However, further research is needed to determine optimal protocols and the long-term efficacy of these techniques [9].

Vibrotherapy

Vibrotherapy is mechanical muscle stimulation that uses vibratory movements with various frequencies and amplitudes to activate the tonic vibration reflex and improve the neuromuscular function of the quadriceps after ACL reconstruction [10].

Vibrotherapy is performed via whole-body vibration or local muscle vibration. The training course includes three sessions per week for 4–8 weeks, with increasing vibration frequency and exercise intensity (from isometric to dynamic exercises). Efficacy criteria: quadriceps strength restoration of ≥15%; limb strength symmetry of >85%; improved functional scores; no severe pain or edema.

Data on vibrotherapy outcomes are contradictory. A meta-analysis by Maghbouli et al. [10] found that whole-body vibration (WBV) considerably improved hamstring peak torque in patients after ACL injury; however, it had a limited effect on quadriceps strength. A systematic review by Rowe et al. [55] found that local muscle vibration at >100 Hz is more effective than WBV for quadriceps strength restoration (effect size: 0.84 vs 0.31). Vibrotherapy can reduce muscle pain and improve the range of motion; however, its long-term effect on muscle strength restoration is limited [56–59].

DISCUSSION

Despite considerable advancements in surgical techniques for ACL reconstruction and rehabilitation programs, AMI remains a major concern, limiting complete functional recovery [6, 9]. This review highlights that AMI is a complex neurophysiological phenomenon, requiring tailored approaches to the diagnosis and treatment for optimal rehabilitation outcomes.

Primary Results

AMI is reported in 43% of patients after ACL injury, with bilateral damage in up to 25% of cases [6]. A central activation ratio of <95% is a reliable diagnostic criterion in AMI, correlating with functional outcomes [6, 18]. Quadriceps activation failure that persists for 12 months after surgery in up to 15%–25% of cases highlights the chronic nature of neuromuscular disorders [18, 19].

The most effective therapeutic options with a moderate evidence level are cryotherapy [6, 9], neuromuscular electrical stimulation [47], and structured exercise programs [49]. Early rehabilitation (within the first week after surgery) is essential for success, with an effect size of 1.48 vs 0.44 in delayed treatment [45].

Neurophysiological Mechanisms

This review confirms the multifaceted nature of AMI, with both spinal and supraspinal mechanisms. Gamma loop dysfunction plays the key role at the spinal level, as evidenced by studies using prolonged vibration [25]. Patients with ACL rupture have an aberrant response of quadriceps muscle spindles to vibration stimulation, indicating impaired Ia afferent feedback and decreased activation of high-threshold motor units [23, 24, 60].

Supraspinal changes detected by neuroimaging indicate considerable motor cortex reorganization [2, 30]. Kapreli et al. [30] reported increased activation of the pre-supplementary motor area and posterior temporal gyrus, indicating a transition from automatic to voluntary motor control. These neuroplastic changes explain why patients after ACL reconstruction have difficulty performing complex motor tasks in sports. These tasks require highly effective automatic motor control [2, 61].

The key characteristics and conclusions of the most relevant studies on the subjects discussed above are summarized in Supplement 1.

Clinical Relevance

Bilateral signs of AMI, which are reported in 25% of cases, have considerable clinical consequences, indicating the need for bilateral rehabilitation even in unilateral injuries [25, 26]. This may explain the limited efficacy of conventional approaches, which focus exclusively on the operated limb [9].

Long-term consequences of AMI include an increased risk of post-traumatic osteoarthritis, as evidenced by 15-year follow-up findings [17, 36, 62]. Patients with persistent AMI have postural control impairment [56], decreased sports performance [63–65], and increased risk of recurrent injuries [66–68].

Diagnosis

Electromyography with superimposed electrical stimulation remains the gold standard for diagnosing AMI [6, 37], with a CAR of <95% serving as a clinically relevant parameter, correlating with functional disorders [6]. Alternative options include isokinetic tests with strength reduction of >15% compared to the contralateral limb [33, 39].

Functional tests, such as the single-leg hop test, strongly correlate with instrumental techniques, with a reduction of >10% indicating AMI [39, 69, 70]. Novel postural control tests using inertial measuring devices show promise in screening for AMI in real-world practice [10, 20].

Treatment

The analysis of therapeutic intervention shows that a multimodal approach that combines various effects on spinal and supraspinal AMI mechanisms is the most effective [45, 45, 22]. Cryotherapy improves EMG activity of the vastus medialis and isometric strength by 38% and 30%, respectively [6]. Neuromuscular electrical stimulation combined with exercise therapy improves muscle strength in both the short and long term [47].

Structured exercise programs must be the first-line therapy, especially within the first week after surgery [49, 50]. Early intervention is essential, as evidenced by significant differences in effect size between early and delayed treatment [45].

One promising technique is transcranial direct-current stimulation, which has been shown to modulate intracortical inhibition and quadriceps training [42]. Biofeedback, especially with visual reinforcement, is superior to conventional exercise therapy in early rehabilitation [51, 53].

Data on vibrotherapy outcomes are contradictory. Local muscle vibration at >100 Hz is more effective than whole-body vibration; however, it has a limited overall effect on quadriceps strength [10, 54].

A personalized approach that considers the severity of disorders, time after surgery, and individual patient characteristics is essential for successful treatment of AMI. Early combination therapy that is continued until a CAR of >95% is achieved delivers the best functional outcomes and reduces the risk of long-term complications [9].

It is currently uncertain whether AMI can be cured, whether its specific manifestations will persist, or whether the condition will relapse [65]. However, the neurophysiological mechanisms of AMI and its resistance or potential persistence indicate that sensory loss due to ACL injury cannot be completely compensated for through other sensory structures [62].

Study Limitations

The key limitations of this study are the interstudy heterogeneity of assessment techniques in AMI, differences in intervention protocols, limited long-term follow-up findings, and the impossibility of meta-analysis due to methodological differences [18, 19, 22].

CONCLUSION

AMI is a complex neurophysiological phenomenon with a considerable impact on functional recovery following ACL reconstruction. This condition is characterized by the involvement of both spinal and supraspinal mechanisms, necessitating multimodal therapeutic strategies. Cryotherapy, neuromuscular electrical stimulation, and exercise programs are the most effective therapeutic options in AMI. Early rehabilitation and combination therapies improve treatment outcomes and decrease the risk of long-term complications. Further research is needed to standardize the diagnosis, develop personalized rehabilitation protocols, and assess the long-term consequences of AMI.

The following guidelines can be provided based on the findings. All patients after ACL reconstruction must be examined for AMI using electromyography with superimposed electrical stimulation because early detection facilitates timely initiation of treatment. Rehabilitation must include cryotherapy, neuromuscular electrical stimulation, and exercise programs and must begin within the first week after surgery. Considering the bilateral manifestation of AMI, rehabilitation must include exercises for both lower limbs, even if the contralateral limb is not affected. Long-term postoperative follow-up is necessary because AMI can persist for months or years after surgery, necessitating adequate rehabilitation.

Further research is needed to standardize the diagnosis and assessment of AMI, develop personalized rehabilitation protocols, and assess the long-term consequences of AMI in terms of the risk of post-traumatic osteoarthritis. Moreover, the role of neuroplasticity in rehabilitation after ACL reconstruction must be investigated, and new neuromodulation techniques for the treatment of AMI must be developed.

ADDITIONAL INFORMATION

Supplement 1. Evidence matrix.

doi: 10.17816/clinpract696935-4403779

Author contributions: A.A. Akhpashev: conceptualization, writing—review & editing; D.V. Skvortsov: conceptualization, validation, writing—review & editing; A.I. Gulyakovich: conceptualization, visualization, writing—original draft. Thereby, all authors provided approval of the version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Acknowledgments: The authors express their gratitude to all researchers whose works were included in this systematic review.

Funding source: The study was conducted as part of a state assignment by the Federal Medical-Biological Agency of Russia.

Disclosure of interests: The authors declare no conflict of interests.

Statement of originality: The authors did not utilize previously published information (text, illustrations, data) in conducting the research and creating this paper.

Data availability statement: The data used in this review can be requested from the corresponding author.

Generative AI: Generative AI technologies were not used for this article creation; translate.google.com was used to translate English-language publications.

About the authors

Dmitry V. Skvortsov

Federal Research and Clinical Center of Specialized Medical Care and Medical Technologies; The Russian National Research Medical University named after N.I. Pirogov

Email: dskvorts63@mail.ru
ORCID iD: 0000-0002-2794-4912
SPIN-code: 6274-4448

MD, PhD, Professor

Russian Federation, Moscow; Moscow

Alexey I. Gulyakovich

Family Clinic ZIM

Author for correspondence.
Email: gulyakovich@gmail.com
ORCID iD: 0009-0001-3689-7417
Russian Federation, Moscow

Alexander A. Akhpashev

Federal Research and Clinical Center of Specialized Medical Care and Medical Technologies; Peoples’ Friendship University of Russia

Email: akhpashev@gmail.com
ORCID iD: 0000-0002-2938-5173
SPIN-code: 9965-1828

MD, PhD

Russian Federation, Moscow; Moscow

References

Supplementary files