Journal of Sport Rehabilitation, 2022, 31, 694-706

https://doi.org/10.1123/jsr.2021-0128
© 2022 Human Kinetics, Inc. NARRATIVE REVIEW

Arthrogenic Muscle Inhibition Following Anterior

Cruciate Ligament Injury
Brian Pietrosimone, Adam S. Lepley, Christopher Kuenze, Matthew S. Harkey,
Joseph M. Hart, J. Troy Blackburn, and Grant Norte

Arthrogenic muscle inhibition (AMI) is a common impairment in individuals who sustain an anterior cruciate ligament (ACL)
injury. The AMI causes decreased muscle activation, which impairs muscle strength, leading to aberrant movement biome-
chanics. The AMI is often resistant to traditional rehabilitation techniques, which leads to persistent neuromuscular deficits
following ACL reconstruction. To better treat AMI following ACL injury and ACL reconstruction, it is important to understand
the specific neural pathways involved in AMI pathogenesis, as well as the changes in muscle function that may impact movement
biomechanics and long-term structural alterations to joint tissue. Overall, AMI is a critical factor that limits optimal rehabilitation
outcomes following ACL injury and ACL reconstruction. This review discusses the current understanding of the: (1) neural
pathways involved in the AMI pathogenesis following ACL injury; (2) consequence of AMI on muscle function, joint
biomechanics, and patient function; and (3) development of posttraumatic osteoarthritis. Finally, the authors review the evidence
for interventions specifically used to target AMI following ACL injury.

Keywords: knee, quadriceps, rehabilitation, ACL, osteoarthritis

Anterior cruciate ligament (ACL) injuries are among the most
common knee-related injuries sustained by physically active in-
dividuals.1 A recent population study from the United States
demonstrated an overall estimated incidence of 69 ACL injuries
per 100,000 person years.2 Younger individuals exhibit a higher
risk of sustaining an ACL injury, with incidence rates peaking
earlier in females (14–18 y of age) compared with males (19–25 y
of age). Furthermore, there has been a rapid growth in the rate of
ACL reconstruction (ACLR) performed in individuals between 13
and 17 years of age between 2002 and 2014 compared with other
age ranges.3 The ACLR seeks to surgically reestablish the liga-
mentous stability of the joint; yet, ACL injured patients often report
persistent disability that leads to decreased sport-related activities
and quality of daily life.4 Specifically, while 82% of individuals
return to some level of physical activity, only 63% of ACLR patients
with an ACLR return to their preinjury physical activity level.5
Following primary ACLR, approximately 7% of individuals sustain
a reinjury to their ACLR limb and another 8% will sustain an injury
to their contralateral limb, indicating a significant need to optimize
rehabilitation for the purpose of minimizing the risk of ACL
reinjury.6 Moreover, 50% of individuals develop posttraumatic
osteoarthritis within 2 decades of ACL injury,7 suggesting that the
most serious consequences of ACL injury may extend long after
completion of formal rehabilitation. In an effort to improve outcomes
following ACLR, substantial research has been conducted to
Pietrosimone and Blackburn are with the MOTION Science Institute, Department of
Exercise and Sport Science, The University of North Carolina at Chapel Hill, Chapel
Hill, NC, USA. Lepley is with the School of Kinesiology, Exercise and Sport
Science Initiative, University of Michigan, Ann Arbor, MI, USA. Kuenze and
Harkey are with the Department of Kinesiology, Michigan State University, East
Lansing, MI, USA. Hart is with the Department of Kinesiology, University of
Virginia, Charlottesville, VA, USA. Norte is with the School of Exercise and
Rehabilitation Sciences, The University of Toledo, Toledo, OH, USA. Pietrosimone
(brian@unc.edu) is corresponding author.
694
optimize rehabilitation in order to facilitate the safe return to physical
activity and prevent posttraumatic osteoarthritis development.
Arthrogenic muscle inhibition (AMI) is an impairment known
to negatively impact rehabilitation outcomes following joint injury
and is traditionally characterized as an ongoing inhibition of unin-
jured musculature surrounding an injured joint.8 AMI commonly
affects the quadriceps in patients recovering from ACL injury and
has been implicated as a key contributor to the development of
altered biomechanics,9,10 patient disability,11,12 and posttraumatic
osteoarthritis.13,14 The pathophysiology of AMI following joint
injury is complex and traditional rehabilitation strategies are often
ineffective for eliminating AMI following ACLR. To better treat
AMI following ACL injury and ACLR, it is important to understand
the specific underlying neural pathways, as well as how AMI may
impact movement biomechanics and long-term structural changes to
joint tissue. This review discusses the current understanding of the:
(1) neural pathways involved in AMI pathogenesis following ACL
injury; (2) consequence of AMI on muscle function, joint biome-
chanics, and patient function; and (3) development of posttraumatic
osteoarthritis. Finally, we review the most current evidence for
interventions specifically used to target AMI following ACL injury.
Neural Pathways Implicated in AMI Etiology
Following ACLR
Previous work demonstrates that AMI is present following ACL
injury compared with uninjured controls and there is considerable
evidence to suggest that AMI does not resolve in all patients
following ACLR.15 However, the neural pathways implicated in
causing the initial onset of AMI may differ from those pathways
linked to the persistent neuromuscular deficits in patients with
ACLR. Although the exact mechanisms are still unknown, evi-
dence suggests that changes in neurophysiological function largely
contribute to AMI and muscle weakness following ACL injury.15,16
After rupture of the ACL, there is a physical disconnection of the
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ligament from the central nervous system (CNS), resulting in
immediate loss of sensory input from damaged mechanoreceptors.
Joint tissue damage also produces an intraarticular inflammatory
response and joint effusion causing other nociceptors and mechan-
oreceptors within the joint to be depolarized.17 These early events
lead to fundamental changes in afferent neurophysiological func-
tion, triggering a cascade of neurological consequences that ulti-
mately result in AMI, or inhibition of the uninjured musculature
surrounding the ACL injured knee.15,16
The initial joint tissue damage and subsequent joint effusion
associated with ACL injury elicit changes in afferent neural
activity, largely through depolarization of 1a, 1b, II, III, and IV
afferent neuronal pathways arising from the injured joint.9,18–22
These changes to afferent function contribute to inhibition of the
quadriceps motor neuron pool, limiting the capacity to generate
muscle contractions during therapeutic exercise in the early stages
of rehabilitation.23,24 Decreased spinal reflexive excitability of the
quadriceps motor neuron pool has been demonstrated in the first
3 months following ACLR and limits the recovery of muscle
strength in the first several months following ACLR.23,24 However,
spinal reflexive excitability of the quadriceps motor neuron pool
resolves as pain and joint effusion diminish overtime24–26 and
quadriceps spinal reflex excitability is equal to uninjured controls at
6 months post-ACLR and at later stages of return to activity.23,26–30
Thus, it is unlikely that spinal reflexive inhibitory mechanisms
contribute to persistent motor neuron inhibition and long-term
impairments in muscle function in patients with ACLR.
There are emerging data to support the working hypothesis that
the early changes in afferent transmission and spinal reflex excitabil-
ity following ACL injury lead to further adaptations in the CNS.15
Advanced neuroimaging studies have demonstrated that patients with
ACL injury have lower activation of sensorimotor areas of the brain,
likely due to the change in input arising from structures of the injured
joint (eg, the native ACL).33–35 Alterations in somatosensation lead to
aberrant changes in function of the motor cortex, which alter the
descending drive to the lower-extremity, that reduce voluntary
muscle activation, and impair coordination of the limb.36,37
Studies using transcranial magnetic stimulation to investigate
the excitability of the primary motor cortex have discovered deficits
in quadriceps corticospinal excitability in ACLR individuals com-
pared with uninjured controls.36,37 Cortical motor thresholds, a
measure of corticospinal excitability that identify the ability to
generate a descending action potential, are reported to be higher
bilaterally in ACL patients compared with healthy controls, indi-
cating that it is more difficult to voluntarily activate the quadriceps
following ACL injury.36,37 In addition, ACLR individuals demon-
strate diminished motor evoked potential magnitudes in the injured
limb compared with the contralateral limb and healthy controls,
representing a loss of overall motor output from the motor cor-
tex.36,37 Further investigation is needed in order to determine the
specific mechanisms leading to the overall changes in cortical
motor excitability; yet, previous studies have demonstrated that
diminished cortical motor excitability is likely a product of both
an increase in intracortical inhibition and a decrease in intracortical
facilitation following ACL injury.38,39 Contrary to the spinal
reflexive origins of diminished quadriceps motor neuron pool
excitability, decreased cortical motor excitability occurs later
following injury and continues for >6 months following ACLR,24
likely contributing to persistent AMI and neuromuscular impair-
ments following ACL injury. Therefore, diminished spinal reflex-
ive excitability, early following ACL injury and ACLR, and
decreased cortical motor excitability, at later postoperative stages,
JSR Vol. 31, No. 6, 2022
AMI and ACL 695
may contribute to the overall quadriceps weakness, activation
failure, and volume loss, observed in many individuals with an
ACL injury.40,41
Linking AMI to Quadriceps Weakness,
Voluntary Activation Deficits, and
Morphological Changes
Quadriceps Weakness
Acute strength deficits exist following ACLR (23%–61% asym-
metry).42–45 Although improvements in strength occur over the
course of rehabilitation,42,44–47 a recent meta-analysis48 reported
moderate to large magnitude deficits in isometric and isokinetic
knee-extension torque of the injured limb through the first 4 months
following ACLR. While quadriceps strength may continue to
improve in the first 1 to 2 years following ACLR,49,50 it is common
for individuals to demonstrate both insufficient (<3.0 N·m/kg11,51)
and asymmetric (>10% compared with the uninjured limb) strength
when returning to unrestricted physical activity. In fact, conven-
tional “pass” rates for isometric and isokinetic knee-extension
torque remain the lowest among the many assessments used to
determine readiness for return to unrestricted physical activity.52–55
In addition, large magnitude deficits in eccentric strength have been
observed from 6 months to >20 years following ACLR,56–59
demonstrating that the impact of ACLR on quadriceps strength
is not contraction mode specific. Although strength recovery of the
injured limb is the clinical priority, several studies24,30,60,61 have
noted strength deficits in the contralateral limb compared with age-
and sex-matched controls, suggesting the presence of bilateral
quadriceps weakness. Although bilateral weakness has not been
consistently observed,40 this finding provides additional evidence
of centrally mediated mechanisms contributing to quadriceps
weakness. Muscle weakness may also be exacerbated by surgical
complications, as previous work has reported that patients who
develop knee arthrofibrosis following ACLR exhibit greater mus-
cle weakness at 4, 7, and 12 months following ACLR.63
While quadriceps strength is often quantified in terms of peak
torque production, the importance of being able to rapidly generate
knee-extension torque in a controlled manner is essential to
dynamic knee stability and force attenuation. A lesser rate of
torque development has been observed from 3 months to more
than 4 years following ACLR,57,61–66 which is concerning given
the concomitant deficits in eccentric strength in these patients.
Specifically, impairments in both early (eg, 0–100 ms) and late
(eg, 100–200 ms) phase rate of torque development are reported in
comparison with either uninjured controls57,61,62 or the contralat-
eral limb.63–66 These findings are particularly interesting as they
suggest the involvement of central (early phase, motor unit recruit-
ment and discharge rate) and peripheral (late phase, fiber type,
muscle volume, and musculotendinous stiffness) adaptations.67
Although much of this work has reported deficits in the injured
limb, a bilateral reduction in early phase rate of torque development
has been observed,61,65 suggesting a CNS contribution to muscle
inhibition. In addition, individuals with ACL injury68–70 produce
more variable knee-extension torque (eg, decreased steadiness
when attempting to maintain a prolonged muscle contraction)
compared with the contralateral limb and to uninjured controls,
which appears to persist for 1–4 years following ACLR.71,72
Clinically, these findings suggest diminished motor control of
the quadriceps, and likely reflect a change in motor unit behavior
during voluntary contractions.
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696 Pietrosimone et al
Voluntary Quadriceps Activation
The collective evidence suggests that adaptations occur within the
CNS following ACL injury and ACLR,36,37,48,73 which contribute
to the muscular impairments commonly observed. From a neuro-
logical perspective, the ability to voluntarily contract skeletal
muscle is dependent on the capacity to recruit motor units of
the corresponding musculature. Unfortunately, individuals who
have experienced an ACL injury are often unable to recruit
quadriceps motor units (ie, activate muscle) to the same degree
as uninjured individuals, a phenomenon termed central activation
failure (CAF).74 Previous investigations40,75 have utilized supra-
maximal percutaneous electrical stimuli applied to either the
femoral nerve (interpolated twitch technique) or quadriceps mus-
culature (superimposed burst technique) during a maximal volun-
tary isometric knee-extension contraction to quantify CAF. In
theory, any additional torque observed due to the electrical stimu-
lation indicates the magnitude of CAF. Normative values76 of
quadriceps activation have been reported for the dominant (95%)
and nondominant (93%) limbs, suggesting that 5% to 7% CAF is
considered normal.
The presence of CAF among individuals who are ACL defi-
cient was first summarized in a 2010 meta-analysis,75 which
reported weighted means of quadriceps activation for the injured
(86.9%) and contralateral (88.6%) limbs from 1 week to 5 years
following injury. These data demonstrated approximately 11% to
13% CAF in both limbs after ACL injury. Interestingly, more than
1 in 2 individuals studied in this analysis demonstrated CAF in the
injured limb, yet about 1 in 3 presented with CAF in the contralat-
eral limb. In fact, bilateral CAF was observed in 21% of this
sample, demonstrating that gross neuromuscular impairments are
not necessarily isolated to the injured limb. More recently, bilateral
CAF has been reported for the injured (16%–17%) and contralat-
eral (12%–19%) limbs from 1 to 24 months following ACL
injury.24,77 Data from electromyographic studies also suggest
that activation of the quadriceps is reduced acutely after ACL
injury, but increased in the hamstrings.78,79 By nature of reciprocal
inhibition, this mechanism may contribute to early reductions in
voluntary quadriceps activation.
Relatively few studies42,43,80,81 have investigated quadriceps
activation during the early recovery from ACLR. Several prospec-
tive investigations have demonstrated improvements in activation
from 1 to 3 months (25%–2% CAF)42 and 3 to 6 months (9% to 7%
CAF)80 following ACLR. However, improvements are not consis-
tently reported during early recovery from ACLR,81 suggesting the
restored ability to voluntarily recruit quadriceps motor units is not
uniformly achieved in rehabilitation. Although asymmetric, these
data do not clearly support the presence of bilateral impairments, as
minimal CAF (0%–8%) is reported in the contralateral limb during
this recovery phase. Voluntary quadriceps activation appears to
improve somewhat from 6 to 12 and 12 to 24 months,48 but persists
beyond the 24-month time point. A recent meta-analysis40 demon-
strates the persistence of CAF from 7 months to 4 years. Large
magnitude deficits in quadriceps activation (13% CAF) are re-
ported in the ACL injured limb compared with controls. Interest-
ingly, CAF is observed bilaterally, with the contralateral limb
demonstrating large magnitude CAF (10%) compared with con-
trols.40 In addition, greater hamstrings excitability is observed
among individuals with a history of ACLR,79 which may perpetu-
ate quadriceps CAF. Lesser quadriceps activation is reported to
associate with lesser knee-extension torque in the contralateral
limbs of individuals beyond 2 years from ACLR,30 suggesting that
persistent CAF may contribute to bilateral quadriceps weakness.
JSR Vol. 31, No. 6, 2022
Thus, caution should be used to ensure that the restoration of
sufficient quadriceps strength remains a clinical goal and to avoid
overreliance on interlimb symmetry indices.
Morphological Changes
The AMI and the inability to adequately activate the quadriceps
potentially leads to changes in its structural/morphological makeup
and often leads to gross atrophy. Several recent reviews41,82
provide evidence of quadriceps morphological changes following
ACL injury. Small to large magnitude deficits in quadriceps cross-
sectional area (CSA) and volume are observed in the injured limb
compared with the contralateral limb from 2 months to 2 years
following ACL injury.41,82 Of these, one study77 assessed individ-
ual muscle volumes, reporting greater volumetric deficits in the
collective vastii musculature (14%–19% asymmetry) compared
with the rectus femoris (5% asymmetry). In addition, this study
demonstrated slightly smaller vasti muscle volumes compared with
a normative database (<1 SD)83 of uninjured individuals. These
findings appear to be supported by several investigations84–86
reporting no between-limb differences in rectus femoris CSA or
volume after ACL injury. However, volumetric differences do not
appear to be uniform between muscles or within a single muscle, as
the collective evidence of individual muscle impairments is con-
flicting.82 Regardless, lesser total quadriceps CSA and volume is
consistently reported in the injured limb after ACL injury, and to a
greater degree in those individuals considered to be candidates for
surgery (ie, noncopers).87
Large magnitude deficits in quadriceps CSA and volume are
observed compared with the contralateral limb from 1 to 3 months
following ACLR.82 Several studies84,88 have reported a decrease in
muscle size from presurgery to 4, 9, and 12 weeks after ACLR
providing clear evidence of quadriceps atrophy during the early
months of recovery. A 21% reduction in rectus femoris CSA has
been observed in the injured limb and to a lesser degree in the
contralateral limb (12%) 9 weeks after surgery.84 Likewise, an
increase in quadriceps volume asymmetry has been observed from
presurgery (6% asymmetry) to 4 (19% asymmetry) and 12 (17%
asymmetry) weeks post-ACLR.88 Small-to-large deficits in quad-
riceps CSA and volume appear to persist from 6 months to 5 years
post-ACLR.29,41,82 Although some evidence appears to indicate a
recovery of muscle size over time,82 large magnitude asymmetries
remain present more than a year later.89 Several studies77,84 have
described atrophy occurring at 7 and 9 months after ACLR near the
time patients are traditionally cleared for unrestricted physical
activity. In contrast, another study77 actually observed a continued
decrease in muscle volumes of the rectus femoris (5%), vastus
lateralis (3%), and vastus medialis (6%) from presurgery to
7 months. Importantly, lesser total quadriceps CSA and volume
are more consistently reported; whereas, deficits among individual
muscles are more variable,82 which appears to suggest a nonuni-
form pattern of morphological adaptations to ACLR. Regardless,
the presence of persistent deficits and atrophy suggests that tradi-
tional strengthening exercises used in rehabilitation may fail to
address the underlying morphological, neurological, and cellular
mechanisms that contribute to muscle atrophy after ACLR.90
Morphological adaptations of the quadriceps are most com-
monly studied; yet, this is not the only muscle group affected by
ACLR. For example, significant atrophy of the semitendinosus and
gracilis are observed among individuals with a hamstrings tendon
autograft,77,82,91 may be linked to harvesting of the graft tissues.
Interestingly, hypertrophy has been observed in muscles proximal
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to the knee (eg, gluteal, obturator externus).77 This may indicate the
presence of a hip-biased mechanism to minimize joint loading at
the knee, while compensating for diminished quadriceps strength
and volume. However, muscle volume does not account for the
quality of muscle tissue, which may be better described by
intramuscular adiposity and fiber type. For example, greater intra-
muscular fat content associate with worse subjective knee function
among individuals recovering from ACLR.62,84 These data suggest
that evaluation of intramuscular fat content by means of ultrasound
imaging may serve as a useful clinical measure. Previous studies
have also reported acute92 and persistent93 atrophy among type IIa
and IIx muscle fibers in the vastus lateralis following ACLR. In
addition to a smaller fiber diameter, a metabolic shift has also been
observed within the vastus medialis, such that the muscle becomes
more endurant.94
Contributions to quadriceps weakness, activation failure, and
volume loss after ACL injury and ACLR are multifactorial and thus
influenced by various patient-specific factors. While certainly not
an exhaustive list, sex,95–97 graft type,98,99 and maturation100,101
have been identified as independent factors influencing the magni-
tude of quadriceps impairment. Women95–97 and patients receiving
a bone–patellar tendon–bone autograft98,99 generally present with
lesser and more asymmetric quadriceps strength than their male or
hamstrings tendon autograft counterparts. The timing of recovery
may also influence the impact of graft type, as patients with bone–
patellar tendon–bone autograft are reportedly weaker and more
asymmetric during the first year of recovery form ACLR than those
with hamstrings tendon autograft, but not beyond 1 year following
ACLR. Patients younger than 18 years old have also demonstrated
weaker quadriceps compared with older patients within the first
year of recovery only. Interestingly, although weaker, pediatric
patients (ie, skeletally immature) demonstrate more symmetric
quadriceps strength than adults.102 Of note, skeletally immature
females appear to be uniquely susceptible to quadriceps impair-
ments, as they are reportedly weaker and more asymmetric than
male counterparts.100
Linking AMI to Changes Movement
Biomechanics and Physical Function
There has been considerable effort to understand the broader effects
of AMI-related muscle weakness on lower-extremity biomechanics
and patient-reported function in individuals with ACL injury. The
AMI is hypothesized to result in persistent muscle weakness
leading to both acute and chronic modification of movement
strategies depending on the severity of the joint injury, the magni-
tude of diminished force generating capacity, and the neurophysi-
ologic source of dysfunction.103 This hypothesis is based on studies
in which an experimental effusion model was utilized to mimic the
effects of joint injury which indicated that an acute effusion alone
resulted in increased hip and knee flexion along with knee-extensor
moments when compared with preeffusion walking gait biome-
chanics.9,10,12 As a result of this work, a number of research groups
have since attempted to characterize the effects of AMI after ACLR
on biomechanics and patient-reported function at a variety of time
points following injury. This section of the review will focus on the
evidence linking altered excitability, muscle strength, and volun-
tary activation to changes in movement biomechanics and physical
function. Previous studies have largely focused on characterizing
the association between measures of AMI and lower-extremity
biomechanics during walking gait or jump landing in individuals
JSR Vol. 31, No. 6, 2022
AMI and ACL 697
with an ACLR.104–108 Several recent review papers conclude that
individuals with ACLR adopt movement patterns that include
smaller peak knee-flexion angles or excursions, smaller or more
asymmetrical knee-extension moments, as well as asymmetrical
vertical ground reaction forces during the stance phase compared
with uninjured controls.109–111 It has been hypothesized that quad-
riceps weakness, diminished quadriceps spinal reflex excitability,
and diminished quadriceps volitional activation may influence the
onset or persistence of this movement pattern following ACLR.
AMI and Gait Biomechanics
In an early investigation into the role of quadriceps strength on gait
following ACLR, Lewek et al105 reported that lesser isokinetic
quadriceps strength symmetry associated with both smaller peak
knee-flexion angles (R2 = .26) and knee-extension moments at peak
knee flexion (R2 = .60) among individuals 4 months post-ACLR.
This study indicated that both sagittal plane kinematics and kinetics
are influenced by quadriceps strength deficits following ACLR.
Blackburn et al104 reported that greater voluntary quadriceps
activation was associated with greater instantaneous heel strike
transient (r = .31) and linear loading rates (r = .33) among indivi-
duals 49 (39) months post-ACLR. While the sample of individuals
with ACLR was relatively heterogeneous based on participant
demographics and surgical characteristics, these findings highlight
the association between impaired quadriceps voluntary activation
and aberrant ACLR limb loading that is reported to be influenced
by ACLR.109,110 More recently, Pietrosimone et al106 dichotomized
individuals 29 (27) months post-ACLR into weak (ACLR limb peak
isometric torque <3.0 N·m/kg) and strong (ACLR limb peak iso-
metric torque ≥3.0 N·m/kg) groups after which they compared early
and late stance walking kinematics and kinetics using functional data
analysis techniques. They found that individuals experiencing mean-
ingful weakness after ACLR walked with greater vertical ground
reaction force vertical ground reaction force(vGRF) during the first
22% of stance and lesser vGRF between 36% and 43% of stance. In
addition, knee-extension moment was significantly greater in strong
participants between 7% and 62% of stance.107 When taken together,
these studies and several others104,108 indicate that measures associ-
ated with AMI may play a role in influencing gait biomechanics after
ACLR with consistent evidence indicating that ACLR limb quadri-
ceps weakness and diminished quadriceps volitional activation are
associated with altered limb loading during the load acceptance and
mid-stance portions of walking gait105,107 which may have implica-
tions for knee joint cartilage health111,112 and patient-reported
function.113,114
AMI and Jump Landing
There is consistent evidence from cross-sectional studies indicating
significant associations between quadriceps function and sagittal
plane landing biomechanics as well as loading during a landing
task.116–119 Ward et al115 found that greater voluntary quadriceps
activation was associated with greater peak internal knee-extension
moment (ρ = −.38), and greater spinal reflexive excitability was
associated with greater peak vGRF (r = .45) during a double limb
drop landing. However, Lisee et al118 did not find a similar
association between quadriceps strength and biomechanics during
a single-leg landing or a single-leg step down task, indicating that
task difficulty or complexity may play a role in moderating the
association between quadriceps muscle function and landing bio-
mechanics. Similar to studies investigating walking gait, the largest
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698 Pietrosimone et al
volume of evidence and most consistent findings available indicate
that greater ACLR limb quadricep strength is associated with
larger or more symmetrical ACLR limb knee-extension mo-
ments,116,119,120 knee-flexion angles or excursions,108,118,120 and
greater or more symmetrical vGRF118,120 during double limb or
single limb landings. It should be noted that there are several
important limitations within the available literature evaluating the
relationship between measures of AMI and lower-extremity func-
tion after ACLR. Importantly, concomitant intraarticular injury
and surgical characteristics, time since ACL injury or ACLR,
participant demographics, and the outcome measures utilized to
characterize both AMI and lower-extremity biomechanics vary
widely between studies, which significantly limits the ability to
draw systematic conclusions regarding the influence of AMI on
lower-extremity biomechanics within commonly studied patho-
logic populations.
AMI and Patient-Reported Function
In cross-sectional studies evaluating the association between quad-
riceps strength and patient-reported function, Pietrosimone et al11
(37 [37] mo post-ACLR) and Kuenze et al51 (32 [24] mo post-
ACLR) have reported that ACLR limb isometric quadriceps
strength greater than 3.1 and 3.0 N·m/kg, respectively, are signifi-
cant predictors of acceptable patient-reported function among
individuals with ACLR, and Sherman et al reported similar find-
ings for quadriceps strength symmetry (limb symmetry index
≥69.4%).120 In a recent prospective cohort study, greater change
in ACLR limb isometric quadriceps strength from presurgery to
return to play explained 59% of the variance in patient-reported
function collected at the time of return to sport.121 Taken together,
these findings from cross-sectional and prospective cohort studies
indicate that involved limb quadriceps strength and symmetry in
quadriceps strength not only associated with walking and landing
biomechanics after ACLR, but also enhancing the individual’s
perception of their functional capacity from months to years
following surgery. Unfortunately, there is limited evidence regard-
ing the association between patient-reported function and both
voluntary quadriceps activation and spinal reflex excitability fol-
lowing ACLR.73 Among the limited available evidence, it does not
appear that either quadriceps volitional activation or spinal reflex
excitability plays an influential role in determining patient-reported
knee function among individuals with ACLR122–125; however,
further investigation is required before a definitive understanding
of this complex interaction can be adopted.
Linking AMI to Knee Osteoarthritis Onset
As established in the prior section, the quadriceps muscles are
important for controlling knee joint loading and knee joint stability.
Therefore, alterations in quadriceps muscle function change the
overall loading across the tibiofemoral joint and place the joint at
risk for osteoarthritis onset. While muscle weakness and AMI are
both common findings in people with diagnosed knee osteoarthri-
tis,125 there is also evidence to suggest that alterations in quadriceps
function precede the development of knee osteoarthritis and
increase the risk for disease onset.125 For example, women who
went on to develop incident knee osteoarthritis within 31 months
presented at a baseline visit with 15% to 18% lower isokinetic
quadriceps strength compared with women who did not develop
osteoarthritis.126 In addition, a study of 3081 participants found that
greater isokinetic quadriceps strength was associated with a 55%
JSR Vol. 31, No. 6, 2022
reduction in risk of self-reporting the development of knee osteo-
arthritis in women, and a 30% reduction in risk in men.127 In
addition to quadriceps muscle strength associating with the onset of
idiopathic knee osteoarthritis, there is a growing body of literature
that links AMI to knee osteoarthritis post-ACLR.14
The ACL injury and ACLR is theorized to result in quadriceps
AMI that leads to muscle weakness, atrophy, and altered activation
strategies.41,75,78,128 These declines in muscle function are associ-
ated with impairments in movement biomechanics and altered joint
loading patterns108,109,125 that ultimately lead to pain, disability,
joint breakdown, and knee osteoarthritis.125 In support of this
theory, isokinetic quadriceps weakness is associated with radio-
graphic tibiofemoral joint space narrowing over 4 years post-
ACLR.129 While these results provide evidence of a longitudinal
relationship between quadriceps weakness and osteoarthritis-
related structural declines, this study used a radiographic measure
of osteoarthritis, which may not provide insight to earliest joint
changes following ACLR. However, a recent study used a more
sensitive imaging marker to determine the association between
quadriceps strength and proteoglycan density (ie, T1 rho MRI).13
This study observed that, as early as 6 months post-ACLR,
quadriceps weakness was associated with altered cartilage compo-
sition (ie, decreased proteoglycan density).13 Similar associations
between quadriceps weakness and collagen disorientation (via T2
mapping MRI) have also been observed in young individuals with
osteoarthritis risk factors.130 These studies highlight the need to
limit the effects of AMI and maximize quadriceps function for the
purpose of maintaining joint health post-ACLR.
Interventions for AMI Following
ACL Injury and ACLR
Traditional rehabilitation for ACL injury has focused on regaining
lower-extremity muscle strength and function for the purpose of
optimizing dynamic movement patterns related to activities of daily
living, physical performance, and re-injury prevention. Persistent
AMI has been viewed as a limiting factor for achieving optimal
rehabilitative gains8 and the inability of traditional rehabilitation to
specifically target AMI may contribute to persistent neuromuscular
deficits following ACL injury and ACLR. For this reason, different
interventions have attempted to target and remove AMI, allowing
patients to utilize a greater degree of muscle function to perform
traditional progressive resistance exercises. Previous work demon-
strates that increasing the ability to voluntarily activate the quadri-
ceps results in a subsequent increase in quadriceps strength,131,132
suggesting that utilizing interventions to decrease AMI in addition
to traditional therapeutic exercise may allow more beneficial
rehabilitation regimens.
Transcutaneous Electrical Nerve Stimulation and
Cryotherapy
Transcutaneous electrical nerve stimulation (TENS)133 and cryo-
therapy134 are commonly used for pain relief; yet, previous studies
have demonstrated the capacity of these modalities to disinhibit the
quadriceps motor neuron pool following experimental knee effu-
sion.135,136 It is hypothesized that TENS and cryotherapy applied to
the injured joint increase depolarization of various cutaneous
receptors or thermoreceptors around the knee joint, respectively,
leading to greater excitatory afferent transmission that may over-
come reflexive inhibition caused by AMI.137 Previous work has
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demonstrated greater quadriceps activation during maximal volun-
tary contractions performed with cryotherapy compared with a
sham treatment following knee surgery.138 A small randomized
controlled trial (N = 30) demonstrated that the addition of TENS
to therapeutic exercise slightly increased the effect sizes for im-
provements in voluntary quadriceps activation and muscle strength
compared with therapeutic exercise alone in individuals with an
ACLR.139 Another small laboratory study (N = 10) found that
2 weeks of therapeutic exercise combined with cryotherapy resulted
in improved voluntary quadriceps activation and muscle strength in
ACLR individuals who were an average of 28 (17) months post-
ACLR.140 While both TENS and cryotherapy demonstrate promise
for directly improving rehabilitation outcomes following ACLR,
larger high quality randomized controlled trials are needed to
determine the overall effectiveness of these interventions.
Vibration Therapy
Vibration appears to have the capacity to enhance quadriceps
function following ACLR. Previous literature indicates that
whole-body vibration and local muscle vibration increase knee-
extension peak torque and reduce quadriceps CAF in individuals
with experimental knee effusion and in individuals with
ACLR.142,143 This enhanced muscle function appears to be the
result of heightened CNS excitability. Vibration acutely increases
quadriceps corticomotor excitability (ie, decreased active motor
threshold and increased motor evoked potential amplitude) in
individuals with ACLR.142 Greater improvements in quadriceps
function with vibration incorporated into standard ACLR rehabili-
tation have been reported compared with standard of care.143,144
These effects are likely attributable to heightened CNS excitability,
as vibration alone likely does not provide the mechanical stimulus
necessary for strength gains.145,146 Furthermore, improvements in
quadriceps function persisted for up to 1 hour following applica-
tion147 such that it could be applied at the beginning of a rehabili-
tation session to “prime” the CNS and potentially enhance the
efficacy of rehabilitative exercises designed to improve quadriceps
function.
Neuromuscular Electrical Stimulation
Neuromuscular Electrical Stimulation (NMES) is one of the most
studied modalities used to treat muscle activation deficits following
ACL injury and ACLR.148,149 The NMES directly stimulates inhib-
ited musculature to increase muscle activation during a voluntary
contraction. The mechanism of action for NMES targets the inhibited
motor units, which differs from the TENS, cryotherapy, and vibration
that seek to increase depolarization of afferent neurons and increase
motor neuron excitability in the CNS.137,150 Previous systematic
reviews148,149 have concluded that the addition of NMES to thera-
peutic exercise results in moderate improvements in muscle strength
compared with traditional therapeutic exercise alone. Hauger et al149
concluded that the strongest NMES effects were found when NMES
was applied after the first week post-ACLR.
Eccentric Exercise
Eccentric training has been reported to exhibit a greater capacity to
increase muscle strength compared with concentric strength train-
ing and can be safely implemented as early as 3 weeks following
ACLR.151 Previous work has eccentrically trained a single limb
and demonstrated improvements in voluntary activation of the
untrained limb, suggesting that eccentric training may impact
JSR Vol. 31, No. 6, 2022
AMI and ACL 699
central neural mechanisms associated with neuromuscular excita-
tion.152 Previous studies have demonstrated increases in quadriceps
muscle strength in ACLR individuals following eccentric training
compared with standard concentric-based therapeutic exercise
protocols.153 Greater quadriceps muscle volumes have been dem-
onstrated at 1 year following ACLR in individuals who underwent
12 weeks of eccentric training compared with those who underwent
traditional therapeutic exercise.154 Furthermore, others have dem-
onstrated that the addition of NMES to 12 weeks of eccentric
exercise provides little benefit for increasing muscle strength
beyond that of 12 weeks of eccentric exercise alone.132
Biofeedback
Electromyography-based biofeedback is a common modality used
to improve muscle function in individuals with knee injuries.155
Electromyography-based biofeedback has demonstrated the ability
to increase cortical motor excitability,156 which is diminished in
ACLR individuals.24,39 A recent small sham-controlled cross-over
study (N = 10) demonstrated that visuomotor biofeedback resulted
in increased cortical motor excitability in individuals with an
ACLR.157 Benefits for muscle strength have been demonstrated
for ACLR patients who utilize electromyography-based biofeed-
back along with therapeutic exercise during the early rehabilitation
process compared with therapeutic exercise without electromyog-
raphy-based biofeedback.158,159 To date, large-scale trials evaluat-
ing the effect of electromyography-based biofeedback on muscle
inhibition following ACLR have not been conducted, and it
remains unknown if electromyography-based biofeedback per-
forms similarly to other disinhibitory intervention options. In
addition, biofeedback administered as gait retraining has been
successfully used to elicit more optimal gait biomechanics follow-
ing ACLR.160,161
Blood Flow Restriction Training
Blood flow restriction (BFR) training is a novel technique that
seeks to limit blood flow to the quadriceps muscle using a
pressurized cuff. It is hypothesized that BFR training allows
patients to elicit benefits with low loads that are typically only
achievable with higher loads. Therefore, BFR may be advanta-
geous for minimizing atrophy in the first weeks following ACLR
when high loading is not indicated during rehabilitation. A recent
systematic review of randomized controlled trials162 concluded that
BFR training may be beneficial in limiting quadriceps atrophy
following ACLR as patients that engaged in BFR demonstrated
less atrophy,163 greater quadriceps CSA measured with magnetic
resonance imaging,164 and improved thigh CSA measured with
dual-energy X-ray absorptiometry165 at time points between
14 days and 16 weeks post-ACLR. Conversely, an 8-week BRF
training intervention paired with high-intensity resistance training
initiated at 10 weeks post-ACLR did not improve quadriceps
torque, quadriceps voluntary activation, and rectus femoris volume
compared with high-intensity training alone.166 These data suggest
that the use of BFR training in the initial weeks following ACLR
may be most beneficial in maximizing benefits from BFR; yet,
more research is needed in this area.
Summary
Quadriceps muscle function is important for optimal physical
performance, lower-extremity biomechanics during multiple
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700 Pietrosimone et al
activities of daily living, and quality of life following ACL injury
and ACLR. The AMI is a neuromuscular impairment associated
with ACL injury and reconstruction that can limit the efficacy of
rehabilitation following ACL injury and ACLR. While the exact
mechanisms causing AMI remain unknown, both alterations in
spinal reflexive and corticospinal neural pathways are involved
in decreasing voluntary quadriceps activation and strength which
leads to decreased muscle volumes over time. Overall, changes in
quadriceps muscle function caused by AMI lead to a stiffened
knee strategy (ie, decreased knee flexion excursion and lesser knee-
extension moments) during walking gait and jump landing biome-
chanics and the eventual increased risk of developing knee osteo-
arthritis. The AMI is a detectable impairment that can be treated
during rehabilitation following ACL injury with a variety of
interventions aimed at sensory neurons to increase excitatory
afferent transmission (eg, TENS, cryotherapy, and vibration) or
exogenously increase activation of the inhibited motor units using
electrical stimulation (NMES). In addition, rehabilitation techni-
ques that utilize eccentric contractions and biofeedback may
increase excitation of the CNS negatively impacted by AMI.
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