Incidence and Risk Factors for Arthrogenic Muscle Inhibition in the Early Postoperative Period After ACL Reconstruction. A Cohort Study From the SANTI Study Group

Abstract

Background:

Arthrogenic muscle inhibition (AMI) is a process in which neural inhibition after injury or surgery to the knee results in quadriceps activation failure and knee extension deficit. A recent study showed that AMI occurs in over half of patients with acute ACL injuries.

Purposes:

To (1) determine the incidence of AMI within the 6 weeks after an anterior cruciate ligament reconstruction (ACLR) and (2) identify the risk factors associated with AMI after an ACLR.

Study Design:

Case-control study; Level of evidence, 3.

Methods:

Consecutive patients who sustained a primary ACLR between January and October 2023 were considered for study inclusion. Eligible patients underwent a standardized physical examination at 3 and 6 weeks postoperatively. This included an assessment of quadriceps inhibition, identification of any extension deficits, and grading of AMI and its clinical reversibility according to the Sonnery-Cottet classification.

Results:

A total of 210 consecutive patients with a primary ACLR were prospectively enrolled in the study. Respectively, 48.6% of patients had AMI at 3 weeks and 24.3% at 6 weeks postoperatively. Among them, 79.4% and 72.5% demonstrated reversible types (grade 1A or 2A), respectively. Multivariate analysis revealed that patients who had a preoperative AMI (odds ratio [OR], 8.27 [95% CI, 4.177-17.138]; P < .001), experienced immediate postoperative pain exceeding 7 out of 10 on the visual analog scale (VAS) (OR, 4.689 [95% CI, 2.144-10.814]; P = .0002), or did not have preoperative physical therapy (OR, 2.303 [95% CI, 1.186- 4.530]; P = .0149) were associated with a significantly greater risk of AMI at 3 weeks postoperatively. No risk factors were found at 6 weeks postoperatively.

Conclusion:

AMI occurs in 48.5% of patients at 3 weeks, and 24.2% at 6 weeks after an ACLR. Important risk factors identified for the presence of AMI at 3 weeks postoperatively included the presence of preoperative AMI, immediate postoperative VAS pain score of >7, and absence of preoperative physical therapy.

Early observations regarding the inhibition of peripheral reflexes after lower limb injury can be traced back to the era of Galen (150 AD) and contemporaneous descriptions of gladiators and their injuries.^1,41,45 Charcot and Raymond better characterized these types of dysfunctions after injury in the 1890s and first evoked a theory of central origin.^3,38,45,51 The basis for a central origin is supported in the contemporary literature, and it has been demonstrated using functional magnetic resonance imaging (MRI) that changes in brain plasticity occur in motor and sensory areas after anterior cruciate ligament (ACL) injury. ¹³ In fact, many studies have reported that cognitive impairments occur after ACL rupture, whether surgery is performed or not.^{36,11,18,22,31} However, previous research focused specifically on the associated motor impairment is sparse.^7,12,14,19

The central motor inhibition, or reflexive quadriceps shutdown in the injured or operated leg, sometimes accompanied by uncontrolled hamstring contracture, has been referred to as “arthrogenic muscle inhibition” (AMI).^39,40 Recent insights into the pathophysiology of this condition provided a better understanding of its mechanism. ³⁹ Neurological disturbances at various levels play a role, beginning with local factors such as inflammation, effusion, pain, and mechanoreceptor destruction, leading to altered sensory afferents. All these reflex mechanisms, whether central or peripheral, are thought to confer a protective effect on the compromised joint by limiting function; however, this can persist beyond the immediate postinjury or postsurgical period and hinder rehabilitation.^{10,17,23,28,36} Nevertheless, there is no consensus regarding standardized management of this condition. A recent scoping review reported that there is moderate-quality evidence for the efficacy of physical exercises and cryotherapy in alleviating quadriceps activation failure after ACL injury or reconstruction (ACLR). ⁴⁹ This suggests that improving the identification of this condition and implementing targeted therapeutic interventions may contribute to reducing the morbidity associated with quadriceps shutdown and hamstring contracture.^{2,5,16,21,33,40,43}

There is a significant and increasing incidence of ACL ruptures. ²⁶ This is important because stiffness-related complications remain a significant and frequent source of postoperative morbidity.^30,54 In 2023, Sonnery-Cottet et al^46,47 proposed a classification for AMI and reported that 56% of patients demonstrated this condition after ACL injury (preoperatively) and identified risk factors. To the knowledge of the authors, the incidence of AMI after ACLR has not been characterized using this clinical classification. Therefore, the objective of this study was to (1) assess the incidence of AMI within 6 weeks after ACLR and (2) identify the associated risk factors. The hypothesis was that AMI is common after ACLR and that factors previously identified as important preoperatively would remain important postoperatively.

Methods

Study Design and Participants

Institutional review board approval (COS-RGDS-2022-11-005-SONNERY-COTTET-B) was granted for this retrospective, nonrandomized, comparative study. Consecutive patients with an ACLR (primary or revision) performed between January and October 2023 were considered for study inclusion if physical examination (Lachman and pivot-shift test) findings and MRI confirmed an ACL injury (including injury to a native ACL or an ACL graft). Patients were excluded if they had fractures in the ipsilateral or contralateral limb, multiligamentary injuries, declined to participate in the study, or presented a chronic irreducible AMI (grade 3).

Preoperatively (C0)

All included patients participated preoperatively in a standardized interview, completed forms for patient-reported outcome measures, including visual analog scale (VAS) pain score, subjective International Knee Documentation Committee score, Lysholm score, Knee injury and Osteoarthritis Outcome Score, Simple Knee Value, and preinjury Tegner activity level. Physical examination included standard knee examination (Lachman and pivot-shift tests), an assessment of anteroposterior side-to-side laxity difference measurement using a Rolimeter (Aircast Europa), and an assessment of AMI based on clinical features of vastus medialis oblique (VMO) inhibition, the presence of extension deficit, and reversibility of these features according to the Sonnery-Cottet classification of AMI. ⁴⁶ The evaluation of the AMI grade was performed by 1 of 4 different experienced orthopaedic surgeons (B.S.C., M.T., J.M.F., B.F.), given the high reproducibility of this clinical classification, as shown in the previous studies.^15,43,44

Clinical classification ⁴⁶ was as follows:

• Grade 0: Normal VMO contraction

• Grade 1A: VMO contraction inhibited, reversible with simple exercises

• Grade 1B: Similar to 1A but requires longer and specific rehabilitation programs

• Grade 2A: VMO contraction inhibited with associated extension deficit, reversible with simple exercises

• Grade 2B: Similar to 2A but refractory to simple exercises, requiring longer and specific rehabilitation programs

• Grade 3: Chronic irreducible extension deficit requiring extensive posterior arthrolysis

The specificity of grades 1B and 2B lies in the fact that, despite the reeducation and activation exercises performed during the initial consultation, sufficient activation of the vastus medialis is ultimately not achieved, consequently requiring supplemental treatment. The classification is determined during the initial treatment.

No patient underwent surgery while exhibiting features of persistent vastus medialis contraction deficit or hamstring contracture. Where appropriate, reduction maneuvers were performed to eliminate this preoperatively. ⁴ Patients who faced more challenges during reduction maneuvers underwent a long physical therapy program based on biofeedback ³⁸ or neuromotor reprogramming^4,6 and were reviewed in consultation by the senior surgeon the day before surgery, to ensure that they could demonstrate active full knee extension and a clinically normal VMO contraction. Patients who were referred without previous physical therapy and did not exhibit features of AMI were not assigned to preoperative physical therapy before surgery.

Postoperative Reeducation Program at 3 and 6 Weeks (C3, C6)

Postoperatively, rehabilitation was focused on ensuring the quality of initial postoperative care. The main objectives were to activate the VMO through biofeedback, allow knee flexion without forcing it, and protect the ligament reconstructions with closed-chain exercises. Range of motion exercises aimed at obtaining full extension while avoiding recurvatum. The rationale behind this protocol was to protect the reconstruction grafts from mechanical stress and allow sufficient motion to prevent arthrofibrosis.

At 3 and 6 weeks, all patients underwent assessment by a sports physician (B.S.C., M.T., J.M.F. or B.F.) trained and familiarized in the recognition and classification of AMI, with the primary objective of collecting data on the presence or absence of AMI. When AMI was present, clinical maneuvers for reducing AMI were executed to categorize the patients into the different grades according to the Sonnery-Cottet classification. ⁴⁶

Statistical Analysis

The sample size was calculated using PASS software with an assumption of patients with a preoperative AMI of 50%, based on previous studies.^8,29,44 A sample size of 210 patients produces a 2-sided 95% CI with a width equal to 14% (ie, a 95% CI around the proportion of [43-57]). Descriptive data analysis was conducted depending on the nature of the criteria. Quantitative data analysis included the number of filled and missing data, mean, standard deviation, median, first and third quartiles, minimum, and maximum. Data comparisons used the Student t test or the Mann-Whitney-Wilcoxon test based on the variable distribution.

Patient data, injury or treatment characteristics, and other potentially important factors associated with ACL mechanical insufficiency were analyzed using a Firth-penalized logistic regression model. The probability of AMI was modeled in relation to the different risk factors.

Variables were included in the initial multivariable model if significantly associated with the dependent variable (AMI status) at a significance level of P = .20 or if they were known prognostic factors in the literature (pain, crutches before visit, effusion, pillow under the knee, previous ACL injury and ipsilateral or contralateral ACL injury). ⁴⁷ The final model resulted from a manual stepwise selection of variables with a significance level of P = .05. The confounding factor was tested.

All comparisons were made at a significance level set at P < .05. All calculations were performed using SAS for Windows Version 9.4 (SAS Institute Inc).

Results

Population and Incidence

A total of 210 patients were prospectively enrolled in the study from January to October 2023. The preoperative demographic and anthropometric cohort included patients with a mean age of 28.3 ± 9.3 years and a body mass index of 24.25 ± 3.02 kg/m². The proportion of men and women was 65% and 35%, respectively. Overall, 38.6% of patients demonstrated signs of AMI (n = 81) in the preoperative period. Patients with grade B (1B, 2B) AMI participated in a specific physical therapy program before undergoing ACLR. In the postoperative period, 48.6% of patients (n = 102) had features of AMI at 3 weeks. Of these, 64.7% had preoperative AMI (P < .001), and 36% of patients with AMI at 3 weeks did not demonstrate signs of AMI at 6 weeks. Overall, the number of patients with signs of AMI decreased to 24.3% at 6 weeks postoperatively (n = 51). Of these, 66.7% had preoperative AMI, and 86% had demonstrated AMI at 3 weeks (P < .001). The incidence and grades of AMI observed are represented in Table 1. Correlation between pre- and postoperative AMI is reported in Table 2.

Table 1.

Incidence and Grade of AMI Before Surgery (N = 210) ^a

	AMI Preop	AMI 3 Weeks	AMI 6 Weeks
Total	38.6	48.6	24.3
Grade 1A	36 (44.4)	49 (48)	28 (54.9)
Grade 1B	17 (21)	12 (11.8)	8 (15.7)
Grade 2A	21 (25.9)	32 (31.4)	9 (17.6)
Grade 2B n	7 (8.6)	9 (8.8)	6 (11.8)

^aData are presented as n (%). AMI, arthrogenic muscle inhibition; Preop, preoperative.

Table 2.

Preop AMI According to AMI at 3 and 6 Weeks for all Patients (N = 210) ^a

	3 weeks, AMI (N = 102)	3 weeks, No AMI (N = 108)	Analyzed Population (N = 210)	P
Presence of preop AMI	102	108	210	<.0001 (chi-2)
No	36 (35.3)	93 (86.1)	129 (61.4)
Yes	66 (64.7)	15 (13.9)	81 (38.6)
	6 Weeks, AMI (N = 51)	6 Weeks, No AMI (N = 159)	Analyzed population (N = 210)	P
Presence of preop AMI	51	159	210	<.0001 (chi-2)
No	17 (33.3)	112 (70.4)	129 (61.4)
Yes	34 (66.7)	47 (29.6)	81 (38.6)

^aData are presented as n (%). AMI, arthrogenic muscle inhibition; Preop, preoperative.

Risk Factors

3 Weeks Postoperative

When looking at the postoperative AMI risk factors at 3 weeks, several factors were studied, including information regarding preoperative conditions, surgery, pain, and therapies. All the factors are included in Table 3.

Table 3.

Descriptive Analysis of Factors Associated With 3 Weeks AMI for all Patients (N = 210) ^a

		No AMI (N = 108)	AMI (N = 102)	Total (N = 210)
Presence of preop AMI	No	93 (72.1)	36 (27.9)	129 (100)
	Yes	15 (18.5)	66 (81.5)	81 (100)
Class of age, y	<20	23 (52.3)	21 (47.7)	44 (100)
	20-30	50 (54.9)	41 (45.1)	91 (100)
	>30	35 (46.7)	40 (53.3)	75 (100)
Sex	Male	67 (49.3)	69 (50.7)	136 (100)
	Female	41 (55.4)	33 (44.6)	74 (100)
Class of BMI, kg/m2	<25	73 (53.3)	64 (46.7)	137 (100)
	≥25	35 (47.9)	38 (52.1)	73 (100)
Delay between trauma and consultation, days	<18	23 (48.9)	24 (51.1)	47 (100)
	≥18	85 (52.1)	78 (47.9)	163 (100)
History of ACL surgery	No	81 (46.8)	92 (53.2)	173 (100)
	Yes	27 (73)	10 (27.0)	37 (100)
Preop knee effusion	No	44 (65.7)	23 (34.3)	67 (100)
	Yes	64 (44.8)	79 (55.2)	143 (100)
Pain score 0-10 at the accident	≤7	86 (58.5)	61 (41.5)	147 (100)
	>7	22 (34.9)	41 (65.1)	63 (100)
Pain score 0-10 at the first visit	≤2	82 (61.2)	52 (38.8)	134 (100)
	>2	26 (34.2)	50 (65.8)	76 (100)
Crutches before the visit	No	69 (53.9)	59 (46.1)	128 (100)
	Yes	39 (47.6)	43 (52.4)	82 (100)
Pillow under the knee at night	No	76 (58.9)	53 (41.1)	129 (100)
	Yes	32 (39.5)	49 (60.5)	81 (100)
Bracing before the visit	No	65 (53.7)	56 (46.3)	121 (100)
	Yes	43 (48.3)	46 (51.7)	89 (100)
Preop physical therapy	No	40 (38.8)	63 (61.2)	103 (100)
	Yes	68 (63.6)	39 (36.4)	107 (100)
Postop aspiration performed at 3 weeks	No	99 (50.8)	96 (49.2)	195 (100)
	Yes	9 (60)	6 (40)	15 (100)
Pain score 0-10 after surgery in the recovery room	≤7	96 (61.9)	59 (38.1)	155 (100)
	>7	12 (21.8)	43 (78.2)	55 (100)
No. of physical therapy sessions at 3 weeks	≤5	79 (49.7)	80 (50.3)	159 (100)
	>5	29 (56.9)	22 (43.1)	51 (100)
Meniscus suture	No meniscus suture	59 (58.4)	42 (41.6)	101 (100)
	MI suture	23 (54.8)	19 (45.2)	42 (100)
	ME suture	9 (25.7)	26 (74.3)	35 (100)
	Suture both menisci	17 (56.7)	13 (43.3)	30 (100)
Use of a commercial cryotherapy device postoperatively	Yes	103 (95.4	56 (54.9)	159 (75.7)
	No	5 (4.6)	46 (45.1)	51 (24.3)

^aData are presented as n (%). AMI, arthrogenic muscle inhibition; BMI, body mass index; Preop, preoperative.

Table 4 presents the factors included in the multivariate model. In summary, multivariate analysis shows that the VAS pain score strictly exceeding 7 out of 10 on the numeric rating scale immediately after surgery, the presence of preoperative AMI, and the absence of preoperative physical therapy were important risk factors for postoperative AMI. Odds ratios were calculated and summarized in Figure 1 and Figure 2

Table 4.

Multivariate Analysis of Factors Associated With 3 Weeks AMI for All Patients (N = 210) ^a

Variables		Multivariate analysis (N = 210 observations)
Item	Comparison	OR	95% CI	P
Presence of preop AMI	Yes vs No	8.273	4.177-17.138	<.0001
Preop physical therapy	No vs Yes	2.303	1.186-4.530	.0149
VAS pain score 0-10 in the recovery room	>7 vs ≤7	4.689	2.144-10.814	.0002

^aAMI, arthrogenic muscle inhibition; OR, odds ratio; Preop, preoperative; VAS, visual analog scale.

Figure 1.

Forest plot of risk factors associated with 3 weeks AMI—All patients (N = 198). AMI, arthrogenic muscle inhibition; OR, odds ratio; Preop, preoperatively.

Figure 2.

Factors influencing the occurrence of AMI after ACLR. AMI, arthrogenic muscle inhibition; OR, odds ratio.

6 Weeks Postoperative

In contrast, after following the same statistical regressions, none of these previous factors was correlated with the presence of AMI at 6 weeks.

Discussion

The main findings of the study were the identification of the incidence of postoperative AMI after ACLR and important risk factors. Specifically, it was observed that almost half (48.6%) of patients demonstrate features of AMI at 3 weeks, and 24.3% at 6 weeks after ACLR. Of those, 79.4% and 72%, respectively, had clinically reversible types with specific exercises (grade 1A or 2A). Important risk factors identified for the presence of AMI at 3 weeks postoperatively included the presence of preoperative AMI (8.2-fold increase in the risk), immediate postoperative (recovery room) VAS pain score of >7 (4.6 times increased risk), and lack of preoperative physical therapy (2.6-fold increased risk). No risk factors were identified for the development of AMI at 6 weeks after ACLR.

In contrast to numerous previous studies that highlight the cognitive impairments after ACLR or rupture,^{11,13,18,22,31,36} this study focused on motor deficits. The recent study conducted by Zunzarren et al ⁵⁶ revealed a persistent neuromuscular activation deficit of 42% in the lower limb at 3 years after ACLR, compared with the contralateral side. This deficit affects not only the quadriceps but also other muscles in the lower limb. However, it is crucial to highlight that the utilized assessment tool, the Biarritz Activation Score-Knee, ²⁵ does not assess AMI but rather focuses on functional aspects.

The present study showed that the incidence of AMI increased by almost 10% between the pre- and postoperative assessments. This may be due to a new state of pain, inflammation, and effusion produced by the surgery.^32,34 Conversely, the preoperative incidence within this patient series may potentially be diminished compared with that delineated by Sonnery-Cottet et al, ⁴⁷ given the briefer interval between the injury and the initial consultation (20 days) as opposed to this cohort (47 days). This temporal discrepancy could afford patients the opportunity to engage in physiotherapeutic interventions targeting quadriceps inhibition, a proposition substantiated by the observation that within this cohort, abstaining from preconsultation physical therapy correlates with a 2.2-fold increased risk of preoperative AMI. Nevertheless, the incidence of preoperative AMI remains close to 50% in both studies, which is an important finding.

The second main finding pertained to the risk factors for postoperative AMI. Patients with a preoperative history of AMI face an 8.2-fold increase in risk of postoperative AMI at 3 weeks. In this cohort, no patient underwent surgery while exhibiting features of persistent vastus medialis inhibition or hamstrings contracture. In addition, this study showed a decreasing frequency of AMI between the 3- and 6-week postoperative appointments. The incidence reduced by nearly 50%, which could potentially be explained by the fact that once recognized, the situation can be clinically reversible. This is an important outcome to highlight for practitioners (sports physicians, rehabilitation physicians, surgeons, and physical therapists) who must be vigilant in detecting AMI during the initial evaluation and in the first postoperative consultation, because these patients are at high risk of AMI and, therefore, at high risk of stiffness-related complications.^35,42,52,54 The high prevalence of postoperative AMI emphasizes the importance of communication about this complication using a common clinical classification^45,46 and education regarding the evidence base for efficacy of interventions. ⁴⁹ Among these therapies, classical electrostimulation and proprioception activities—although frequently used in clinical practice as a principal treatment—have been reported to be ineffective.^9,19,48

It is the opinion of the authors that surgery should not be performed in the presence of quadriceps inhibition and/or hamstrings contracture. In cases where there is a large hemarthrosis, we recommend joint aspiration, which provides immediate benefit in terms of pain and motor inhibition.^24,50,55 Biofeedback and surface electromyography (EMG) can also be used in the early diagnosis and treatment of knee AMI. ⁴¹ These programs involved electromyographic biofeedback using a specific device (converting the action potential of the quadriceps into feedback signals of a visual or auditory nature, and thus, it can affect the patient's voluntary task) and neuromotor reprogramming treatment based on the use of proprioceptive sensations associated with motor imagery and low-frequency sounds.^20,27,37 These recent new therapies, used in nearly 25% of cases in the preoperative cohort, and the efficacy of physical therapy exercises, may partially explain why the absence of preoperative physical therapy correlates with a 2.3-fold increased risk of AMI. In addition, it should be emphasized that preoperative AMI was a significant risk factor for postoperative AMI, even among patients who underwent preoperative physical therapy, highlighting the importance of addressing AMI comprehensively before surgery.

Another significant discovery in this study was that patients with an immediate postoperative pain score >7 are 4.6 times more likely to have AMI at 3 weeks. The management of postoperative analgesia should be multidisciplinary to enhance outcomes. The use of cryotherapy/compression braces could be useful in the prevention of AMI by reducing joint effusion and knee pain. While the statistical validation of this proposition is undermined by the insufficient number of patients in the non-AMI group who abstained from their use, our examination reveals that within the AMI group, 50% of patients refrained from employing them. Pain as a risk factor for AMI, both pre and postoperatively, appears to be associated with the findings of the upcoming functional brain MRI study, which may reveal activated motor areas in the AMI group correlated with regions of the brain associated with pain. ⁴⁵

Extension deficit in the early period after ACLR leads to a significantly increased risk of reoperation for stiffness-related complications. ^{5,16,21,33,40,43,53}

In our experience, if rehabilitation is focused on AMI-specific exercises, nearly 50% of cases can resolve by 6 weeks postoperatively, using specific approaches to fatigue the hamstrings and improve quadriceps activation, while influencing neural modulation, providing biofeedback, and facilitating motor excitability. ⁴¹

Limitations

Limitations of this study include its unicentric design. Moreover, not all risk factors were analyzed, such as the type of regional anesthesia and postoperative pain medication used, compliance with physical therapy and rehabilitation programs, the time from injury to surgery, or the type of graft used (most patients were treated with hamstring tendon autografts). In addition, patients with grade 3 AMI were excluded because their diagnosis requires much longer follow-up periods that extend beyond the scope of this study. These patients may demonstrate different characteristics, and thus, the findings of this study cannot be extrapolated to them. Furthermore, although inter- and intraobserver reliability has previously been studied, it was not evaluated in the present study. Another limitation was the absence of a control group in which treatment to abolish AMI was not offered; however, given the author’s belief that these exercises are invaluable in reducing morbidity, it would be unethical to have included such a group. Finally, the proposed classification has the purpose of clinical diagnosis and treatment of acute or severe AMI in pre- or post-ACL surgery, and, even if this visual classification has recently been validated by surface EMG, ¹⁵ further studies are needed to better understand the entire spectrum of AMI.

Conclusion

AMI occurs in 48.5% of patients at 3 weeks, and 24.2% at 6 weeks after an ACLR. Important risk factors identified for the presence of AMI at 3 weeks postoperatively included the presence of preoperative AMI, immediate postoperative VAS pain score of >7, and lack of preoperative physical therapy.