Content available from Sports Medicine
This content is subject to copyright. Terms and conditions apply.
Sports Medicine (2021) 51:321–338
Neuromuscular Function oftheKnee Joint Following Knee
Injuries: Does It Ever Get Back toNormal? ASystematic Review
BeyzaTayfur1 · ChedsadaCharuphongsa1· DylanMorrissey1,2· StuartCharlesMiller1
Published online: 27 November 2020
© The Author(s) 2020
Background Neuromuscular deﬁcits are common following knee injuries and may contribute to early-onset post-traumatic
osteoarthritis, likely mediated through quadriceps dysfunction.
Objective To identify how peri-articular neuromuscular function changes over time after knee injury and surgery.
Design Systematic review with meta-analyses.
Data Sources PubMed, Web of Science, Embase, Scopus, CENTRAL (Trials).
Eligibility Criteria for Selecting Studies Moderate and high-quality studies comparing neuromuscular function of muscles
crossing the knee joint between a knee-injured population (ligamentous, meniscal, osteochondral lesions) and healthy
controls. Outcomes included normalized isokinetic strength, muscle size, voluntary activation, cortical and spinal-reﬂex
excitability, and other torque related outcomes.
Results A total of 46 studies of anterior cruciate ligament (ACL) and ﬁve of meniscal injury were included. For ACL injury,
strength and voluntary activation deﬁcits were evident (moderate to strong evidence). Cortical excitability was not aﬀected
at < 6months (moderate evidence) but decreased at 24+ months (moderate evidence). Spinal-reﬂex excitability did not
change at < 6months (moderate evidence) but increased at 24+ months (strong evidence). We also found deﬁcits in torque
variability, rate of torque development, and electromechanical delay (very limited to moderate evidence). For meniscus
injury, strength deﬁcits were evident only in the short-term. No studies reported gastrocnemius, soleus or popliteus muscle
outcomes for either injury. No studies were found for other ligamentous or chondral injuries.
Conclusions Neuromuscular deﬁcits persist for years post-injury/surgery, though the majority of evidence is from ACL
injured populations. Muscle strength deﬁcits are accompanied by neural alterations and changes in control and timing of
muscle force, but more studies are needed to ﬁll the evidence gaps we have identiﬁed. Better characterisation and therapeutic
strategies addressing these deﬁcits could improve rehabilitation outcomes, and potentially prevent PTOA.
Trial Registration Number PROSPERO CRD42019141850.
Electronic Supplementary Material The online version of this
article (https ://doi.org/10.1007/s4027 9-020-01386 -6) contains
supplementary material, which is available to authorized users.
* Beyza Tayfur
1 Sports andExercise Medicine, Queen Mary University
ofLondon, London, UK
2 Physiotherapy Department, Barts Health NHS Trust,
Neuromuscular alterations are evident in both short- and
long-term following knee injuries in strength, voluntary
activation, cortical and spinal excitability, and in timing
and control of muscle force production.
These alterations may be speciﬁc to ACL injury, since
we could not identify long-term alterations for meniscus
injury and no studies could be found for other ligamen-
tous or cartilage injuries to the knee, indicating a huge
322 B.Tayfur et al.
Knee injury is an independent risk factor for the develop-
ment of knee osteoarthritis (OA) in young adults [1–3]. The
prevalence of post-traumatic OA (PTOA) can be as high as
80% at 10+ years after the initial injury , with 4–6 times
higher odds compared to a non-injured knee . PTOA
mainly aﬀects a younger and more active population when
compared to non-traumatic OA, resulting in longer years
lived with disability , and surgical interventions 7–9years
earlier in life . Therefore, prevention strategies for PTOA
development require particular attention.
Multiple anatomical, molecular, and physiological fac-
tors contribute to PTOA development . Starting from the
energy absorption at the time of trauma, damage to joint
structures, including ligaments, meniscus, cartilage and sub-
chondral bone singly or in combination, creates an inﬂam-
matory cycle. This cycle of activation of cartilage-degrading
enzymes and chondrocyte apoptosis with joint instability
and biomechanical alterations may further contribute to the
degenerative process . Throughout this process starting
from the initial injury to PTOA initiation, it is important to
identify modiﬁable risk factors so that targeted preventive
rehabilitation strategies can be applied.
Muscles around the knee joint play an important role in
the biomechanical alterations and joint instability after a
knee injury. Quadriceps muscle weakness is a modiﬁable
risk factor for non-traumatic OA  and PTOA . Deﬁcits
in quadriceps strength are also common following knee inju-
ries [9, 10], evident even at the end of the initial rehabilita-
tion period , and may persist for more than 20years .
Quadriceps weakness is also associated with gait alterations
following knee injuries , which are common in the long-
term , and hypothesised to be a contributor to PTOA
initiation by abnormal knee cartilage loading . These
biomechanical alterations and joint instability may further
contribute to the degenerative cycle within the knee joint
. Therefore, exercise therapy is at the core of PTOA pre-
vention strategies to theoretically delay or prevent PTOA
onset, through increasing muscle strength and improving
neuromuscular function [16, 17].
While longitudinal data are available for quadriceps
strength, less often considered is the overall neuromuscular
function of the knee joint. Neuromuscular alterations after
knee injury have been reported in case–control studies for
strength , voluntary activation , cortical and spi-
nal neural pathways [9, 10, 20], muscle structure  and
muscle activation patterns [22, 23] in muscles including the
quadriceps [9, 10, 18–21], hamstrings [22, 23] and gastroc-
nemii . Knee joint loading is also not only determined by
quadriceps femoris muscle but by the interaction of quadri-
ceps, hamstrings, gastrocnemius and soleus muscles .
The neuromuscular alterations in these muscles controlling
the knee joint may exacerbate the degenerative process after
a knee injury through muscle weakness and abnormal car-
tilage loading . It is therefore important to comprehen-
sively understand neuromuscular alterations in all the mus-
cles controlling the knee joint. This would further facilitate
improved rehabilitation programs targeting these alterations.
Previous systematic reviews of this type of research typi-
cally considered isolated muscles, particular injuries, spe-
ciﬁc time-points or limited neuromuscular outcomes [19,
25–28]. There is a need to consider the importance of all
injuries on all peri-articular knee muscles, the focus of this
review, to fully understand the consequences of injury and
possible links to PTOA. This review also aimed to identify
where the main gaps in the literature manifest, so that future
research and clinical recommendations can be optimally
Injuries to knee ligaments, meniscus or cartilage are sig-
niﬁcantly associated with higher PTOA risk when compared
to unspeciﬁed injuries [1–3, 29]. Therefore, the injured
population should include ligament, meniscus and cartilage
injuries to the knee if the aim is to understand the asso-
ciation with PTOA development. There is also evidence of
bilateral neuromuscular changes following unilateral knee
injury [30, 31], suggesting a requirement for healthy control
groups instead of using the contralateral ‘healthy leg’ for an
unbiased evaluation of post-traumatic neuromuscular altera-
tions. Therefore, we aimed to determine how neuromuscular
function of the knee joint changes over time following knee
injuries involving ligament, meniscus or cartilage compared
to healthy controls.
This systematic review and meta-analysis complied with the
PRISMA (Preferred Reporting Items for Systematic Reviews
and Meta-Analyses) guidelines . The study protocol was
registered on PROSPERO (International Prospective Register
of Systematic Reviews) (CRD42019141850, 25 July 2019).
2.1 Search Strategy
We conducted a comprehensive systematic search of the fol-
lowing electronic databases without date restrictions until Feb-
ruary 2020: PubMed, Embase, Web of Science, Scopus, and
Cochrane Central Register of Controlled Trials (CENTRAL).
The search terms included medical subject headings (MeSH)
terms and text words. We modiﬁed the search strategy for
each speciﬁc database with keywords and concepts remain-
ing identical. The main concept included (knee injury [anterior
cruciate ligament (ACL), posterior cruciate ligament (PCL),
medial collateral ligament (MCL), lateral collateral ligament
Neuromuscular Function Following Knee Injuries: Does It Ever Get Back to Normal?
(LCL), meniscus, cartilage, chondral] AND neuromuscular
[strength, reﬂex, activation, electromyography, size] AND
lower limb muscles [quadriceps, hamstring, gastrocnemius,
soleus, popliteus]). Search strategies for all databases can be
found in Electronic Supplementary Material Appendix S1.
Two reviewers (BT and CC) independently conducted the
searches, removed duplicates, screened all abstracts for eli-
gibility and retrieved full-text versions of the eligible articles.
Disagreements between reviewer’s judgements were resolved
with a third reviewer (SCM). We also searched the reference
lists of the included articles and of the systematic reviews for
2.2 Selection Criteria
Studies comparing neuromuscular function of the knee joint
in participants with a previous knee injury and/or knee sur-
gery (all ligamentous, meniscal, osteochondral lesions) to an
age- and sex-matched control group were eligible for inclu-
sion. Studies without a control group, comparing involved
limb to uninvolved limb of participants, were excluded, as
there is evidence of bilateral neuromuscular changes follow-
ing unilateral injury [30, 31]. Observational studies both with
cross-sectional or prospective designs and interventional stud-
ies were included. We only used the baseline data of interven-
tional studies. Only studies published in the English language
2.3 Outcome Measures
Studies had to report at least one of the following neuromus-
cular outcome measures as the main outcome to be included:
body-mass normalized muscle strength as measured by an
isokinetic dynamometer or ﬁxed force transducer, torque
related outcomes such as rate of torque development, torque
variability or electromechanical delay, muscle size or vol-
ume, voluntary activation deﬁcits as measured by central
activation ratio or twitch interpolation technique, spinal
reﬂex excitability, or corticomotor excitability as measured
by active motor threshold. We deﬁned neuromuscular as
including muscle size or volume, spinal reﬂex excitability
and corticomotor excitability although we are aware that
others may deﬁne it as outcomes speciﬁcally related to the
force-generating capacity of the muscles.
2.4 Methodological Quality Assessment
Risk of bias of the included studies was assessed using a
modiﬁed version of the Downs and Black checklist [33,
34], a methodological quality assessment tool for both ran-
domised and non-randomised interventional studies with
high internal consistency and inter-rater reliability .
The modiﬁed version consists of 15 questions, excluding
the questions about randomisation and interventions from
the original version (Electronic Supplementary Material
Appendix S2). The highest score of the modiﬁed version is
16, and thresholds for low, moderate and high quality were
accepted as < 60% (≤ 9), 60–74% (10–11), and > 75% (≥ 12),
respectively, consistent with previous studies [14, 35]. We
excluded low-quality studies from this systematic review as
they may cause over- or under-estimation of eﬀect sizes and
may distort results, therefore leading to incorrect conclu-
sions [36, 37]. Two independent reviewers (BT and CC)
assessed methodological quality and disagreements were
resolved by asking a third reviewer (SCM).
2.5 Data Extraction
Data regarding the study design, participant characteristics
(number of participants, age, sex, injury/surgery details,
time since injury/surgery) and outcome measures (meas-
ured muscle groups and outcome) were extracted by two
independent reviewers (BT and CC) in an Excel spreadsheet.
Disagreements were resolved by asking a third reviewer
(SCM). Group means and standard deviations were extracted
for the main outcome measures. Where the reported data
were insuﬃcient, corresponding authors were contacted by
e-mail to request unreported data or additional details.
2.6 Data Analysis
We analysed data according to time since injury/surgery,
consistent with previous systematic reviews [14, 27], as fol-
lows: (1) less than 6months (< 6months); (2) 6months to
less than 12months (6–12months); (3) 12months to less
than 2years (1–2years); and (4) 2years and over (≥ 2years).
When pre-surgery data were reported in surgical treatment
papers, time since injury was used to determine the time
subgroup of pre-surgery data and time since surgery was
used for the post-surgery data.
Data were pooled for meta-analysis when there were
more than two studies reporting the same outcome measure,
using the Cochrane Review Manager software (Version 5.3.
Copenhagen: The Nordic Cochrane Centre, the Cochrane
Collaboration, 2014). Standardised mean diﬀerences (SMD;
Hedges’ adjusted g) with 95% conﬁdence intervals (CIs) were
calculated for variables of interest as the diﬀerence between
the injured leg and healthy control leg. Heterogeneity of the
pooled data was analysed with I2 and was considered as no
heterogeneity (≤ 25%), low heterogeneity (> 25%), moder-
ate heterogeneity (> 50%), and high heterogeneity (> 75%)
. We used ﬁxed (for homogenous data, I2 ≤ 25%) or ran-
dom (for heterogeneous data, I2 > 25%) eﬀects models for
each meta-analysis according to the statistical heterogeneity.
The magnitude of the pooled SMD was interpreted based on
Cohen’s criteria, where SMD ≥ 0.8 indicated large, 0.5–0.8
324 B.Tayfur et al.
moderate, and 0.2–0.5 small eﬀect sizes . Potential pub-
lication biases were also examined by funnel plots for meta-
analyses when 10 or more studies were included . Level
of evidence was reported by the following criteria: strong
evidence (multiple high-quality studies that were statistically
homogenous); moderate evidence (multiple studies including
at least one high-quality study, or from multiple moderate-
quality studies that are statistically homogenous); limited
evidence (high-quality study or multiple moderate-quality
studies that are statistically heterogeneous); very limited evi-
dence (one moderate-quality) .
We also provided an evidence gap map, showing the level
of evidence of available literature with ﬁndings, and areas
that need further research. This aims to avoid research waste
in areas with strong evidence and guide future studies.
3.1 Study Selection
The search strategy retrieved 22,496 papers after duplicate
removal (Fig.1). Following title and abstract screening, 374
articles were assessed in full-text and 137 studies were eli-
gible to undergo quality assessment.
Following quality assessment, 84 low-quality studies
were excluded, leaving 13 high-quality (HQ) and 38 mod-
erate-quality (MQ) studies for ﬁnal inclusion. Details of
methodological quality assessment of included studies can
be found in Table1 and of excluded studies in Electronic
Supplementary Material Appendix S3.
Fig. 1 Flow diagram of the
study selection process
Neuromuscular Function Following Knee Injuries: Does It Ever Get Back to Normal?
Table 1 Methodological quality assessment of included studies based on a modiﬁed Downs and Black scale [33, 34]
Numbers in the top row are the item numbers in the original Downs and Black scale
H high quality, M moderate quality
Study 1 2 3 5 6 7 10 11 12 15 18 20 21 22 25 Total score Quality level
Almeida etal.  1 1 1 1 1 1 1 1 0 0 1 1 1 0 0 11 M
Chung etal.  1 1 1 2 1 1 1 1 0 0 1 1 1 0 1 13 H
Clagg etal.  1 1 1 1 1 1 1 0 0 0 1 1 1 0 0 10 M
Engelen-van Melick etal.  1 1 1 2 1 1 0 1 0 0 1 1 0 0 1 11 M
Freddolini etal.  1 1 1 2 1 1 1 0 0 0 1 1 0 0 1 11 M
Garrison etal.  1 1 1 1 1 1 1 0 0 0 1 1 0 0 1 10 M
Goetschius and Hart  1 1 1 2 1 1 1 0 0 0 1 1 0 0 0 10 M
Goetschius etal.  1 1 1 2 1 1 1 0 0 0 1 1 1 0 1 12 H
Hall etal.  1 1 1 1 1 1 1 0 0 0 1 1 1 0 0 10 M
Harkey etal.  1 1 1 2 1 1 1 0 0 0 1 1 1 0 1 12 H
Holsgaard-Larsen etal.  1 1 1 2 1 1 1 0 0 0 1 1 1 1 1 13 H
Hsiao etal.  1 1 1 1 1 1 0 1 1 0 1 1 1 0 0 11 M
Hsieh etal.  1 1 1 1 1 1 1 0 0 0 1 1 1 0 0 10 M
Ilich etal.  1 1 1 2 1 1 1 0 0 0 1 1 1 0 0 11 M
Johnson etal.  1 1 1 2 1 1 1 0 0 0 1 1 0 0 0 10 M
Kaminska etal.  1 1 1 1 1 1 1 0 0 0 1 1 1 0 0 10 M
Kellis etal.  1 1 1 1 1 1 0 1 0 0 1 1 1 0 0 10 M
Kline etal.  1 1 1 1 1 1 1 0 0 0 1 1 1 0 0 10 M
Krishnan and Williams  1 1 1 2 1 1 1 0 0 0 1 1 0 0 1 11 M
Kuenze etal.  1 1 1 2 1 1 0 1 0 0 1 1 1 0 1 12 H
Kuenze etal.  1 1 1 2 1 1 1 0 0 0 1 1 1 1 1 13 H
Kvist etal.  1 1 1 1 1 1 1 1 0 0 1 1 0 0 0 10 M
Larsen etal.  1 1 1 2 1 1 0 1 0 0 1 1 1 0 0 11 M
Lepley etal.  1 1 1 2 1 1 1 0 0 0 1 1 1 0 1 12 H
Lepley etal.  1 1 1 2 1 1 1 0 0 0 1 1 1 0 1 12 H
Lepley etal.  1 1 1 2 1 1 1 0 0 0 1 1 0 0 1 11 M
Maeda etal.  1 1 1 2 1 1 1 0 0 0 1 1 0 0 1 11 M
Norte etal.  1 1 1 2 1 1 1 0 0 0 1 1 1 0 0 11 M
Oeﬃnger etal.  1 1 1 1 1 1 1 1 0 0 1 1 0 0 0 10 M
O’Malley etal.  1 1 1 1 1 1 1 1 0 0 1 1 0 0 0 10 M
Pamukoﬀ etal.  1 1 1 2 1 1 1 0 0 0 1 1 0 0 1 11 M
Pamukoﬀ etal.  1 1 1 2 1 1 1 0 0 0 1 1 0 0 1 11 M
Reed-Jones and Vallis  1 1 1 1 1 1 1 0 0 0 1 1 1 0 0 10 M
Ristanis etal.  1 1 1 2 1 1 1 0 0 0 1 1 0 0 1 11 M
Roos etal.  1 1 1 2 1 1 1 0 0 0 1 1 0 0 0 10 M
Scheurer etal.  1 1 1 2 1 1 1 0 0 0 1 1 0 0 1 11 M
Sturnieks etal.  1 1 1 2 1 1 1 0 0 0 1 1 0 0 1 11 M
Tengman etal.  1 1 1 2 1 1 1 1 0 0 1 1 1 0 1 13 H
Thomas etal.  1 1 1 2 1 1 1 0 0 0 1 1 0 0 1 11 M
Thorlund etal.  1 1 1 2 1 1 1 1 0 0 1 1 1 1 0 13 H
Thorlund etal.  1 1 1 1 1 1 1 1 1 0 1 1 1 0 0 12 H
Tourville etal.  1 1 1 1 1 1 1 0 0 0 1 1 1 1 1 12 H
Tsarouhas etal.  1 1 1 1 1 1 1 1 0 0 1 1 0 0 0 10 M
Vairo  1 1 1 2 1 1 1 1 0 0 1 1 0 0 1 12 H
Vairo etal.  1 1 1 2 1 1 1 0 0 0 1 1 0 0 1 11 M
Ward etal.  1 1 1 1 1 1 1 1 0 0 1 1 1 0 0 11 M
Welling etal.  1 1 1 1 1 1 1 0 0 0 1 1 1 0 0 10 M
Xergia etal.  1 1 1 2 1 1 1 0 0 0 1 1 0 0 0 10 M
Zarzycki etal.  1 1 1 1 1 1 1 0 0 0 1 1 0 0 1 10 M
Zult etal.  1 1 1 2 1 1 1 0 0 0 1 1 0 0 1 11 M
Zwolski etal.  1 1 1 1 1 1 1 0 0 0 1 1 1 0 1 11 M
326 B.Tayfur et al.
Neuromuscular Function Following Knee Injuries: Does It Ever Get Back to Normal?
3.2 Study Characteristics
The characteristics of the included studies and outcome
measures in each study can be found in Electronic Supple-
mentary Material Appendix S4. Overall, 46 studies included
patients with ACL injury and ﬁve studies included patients
with a meniscus injury. ACL studies included patients with
ACL deﬁcient knees and ACL reconstruction patients with
diﬀerent graft types (i.e. hamstring tendon graft (HT), patel-
lar tendon graft (PT), allograft), while all meniscus studies
included patients who had had a meniscectomy. ACL stud-
ies included a younger population (i.e. participants in their
20s) when compared to meniscus studies (i.e. participants
in their 40s) at the time of testing. We could not identify any
studies including patients with other ligamentous injuries to
the knee (i.e. PCL, MCL, and LCL) or cartilage/chondral
injuries as isolated injuries. In addition, studies generally
tested quadriceps and hamstring muscles, with no studies
reporting any outcomes pertaining to the gastrocnemius,
soleus or popliteus muscles.
Initial meta-analyses showed that injury type caused large
heterogeneity in the pooled data (i.e. opposing direction
of eﬀects based on injury type). Therefore, we performed
our meta-analyses for studies of ACL and meniscus injury
separately. ACL-deﬁcient and ACL-reconstructed cohorts
yielded similar results and did not cause heterogeneity;
therefore, they were pooled together in all meta-analyses.
The overall ﬁndings (direction, eﬀect size and level of
evidence) of all meta-analyses for each outcome measure for
the given time period post-injury/surgery were summarised
in evidence gap maps (Fig.2 for ACL studies and Fig.3 for
meniscus studies). We broke down the ﬁrst 6months in more
detail to show the evidence gap for the post-injury rehabili-
tation period. However, the data for the ﬁrst 6months are
pooled together in the meta-analyses and the gap map is only
showing which months the data are derived from. We could
not identify any publication bias for eligible outcomes (i.e.
with more than ten studies in the meta-analysis; quadriceps
isometric strength) as measured by funnel plots. The forest
plots for quadriceps cortical excitability (Fig.4), quadri-
ceps spinal excitability (Fig.5), quadriceps voluntary activa-
tion (Fig.6), quadriceps slow concentric strength (Fig.7),
and hamstring slow concentric strength (Fig.8) for ACL
studies are presented. All other meta-analyses, forest plots
and funnel plots can be found in Electronic Supplementary
Material Appendix S5.
Our results showed consistent quadriceps and ham-
string strength deﬁcits in both the short- and long-term
after ACL injury/surgery regardless of contraction type
(i.e. isometric, concentric or eccentric) with moderate and
strong evidence. These deﬁcits were in parallel to voluntary
activation deﬁcits in the short- (limited evidence) and long-
term (moderate evidence). Cortical and spinal excitability
were not aﬀected in the short-term (moderate evidence);
however, they were altered in the long-term diﬀerently.
Cortical excitability decreased in the long-term (moderate
evidence), while spinal excitability increased (strong evi-
dence). Muscle size was reported in only one study, provid-
ing very limited evidence of no long-term change. Other
ﬁndings for the quadriceps femoris muscle for patients
with ACL injury/surgery included decreased rate of torque
development (limited to very limited evidence), decreased
(< 6months) then increased (6–12months) time to peak
torque (very limited evidence), increased torque variability
(very limited to moderate evidence), and unaﬀected elec-
tromechanical delay (very limited evidence). Additionally,
hamstring rate of torque development was not aﬀected
(very limited evidence); however, electromechanical delay
increased in the long-term (limited to moderate evidence).
No change was seen in hamstring to quadriceps strength
ratios (very limited to moderate evidence).
Meniscus studies reported quadriceps and hamstring
strength deﬁcits in the short-term (i.e. the ﬁrst 6months after
injury/surgery), with quadriceps strength greater than controls
in the second year following injury/surgery, and similar to con-
trols in the long-term (i.e. 24+ months post injury/surgery),
albeit with limited or very limited evidence. Also, no change
was reported for quadriceps rate of torque development in the
long-term (limited evidence). Other neuromuscular outcomes
for meniscus injuries have not been investigated, leaving a
huge evidence gap for this voluminous patient population.
Neuromuscular alterations around the knee joint are com-
monly reported following knee injuries but remain poorly
understood due to lack of adequate synthesis. The aim of this
systematic review was to identify changes in neuromuscular
function of the knee joint over time following knee injury/
surgery. Central and peripheral neural changes, morphologi-
cal muscle changes, and the clinical manifestations of altered
amplitude and timing of muscle activation and torque control
were included in the analysis to provide a comprehensive
overview. The timeline of these changes was also provided,
enabling the comparison of short- and long-term changes
after injury. Following ACL injuries, we found evidence for
Fig. 2 Findings and literature gap map for anterior cruciate ligament
studies. Colours represent the evidence level as by van Tulder etal.
 and directions represent injured group data when compared to
control, with the eﬀect size. SMD standardised mean diﬀerence, ST
semitendinosus, BF biceps femoris, Ham:Quad hamstring:quadriceps
328 B.Tayfur et al.
Neuromuscular Function Following Knee Injuries: Does It Ever Get Back to Normal?
deﬁcits in quadriceps and hamstring strength and quadriceps
voluntary activation, changes in cortical and spinal-reﬂex
neural pathways, deﬁcits in force control and delays in rapid
force generation post-injury. Following meniscus injuries,
there was limited evidence for immediate strength deﬁcits,
with these being restored long-term. Importantly, we iden-
tiﬁed major gaps in the evidence base, with no studies on
patients with cartilage injuries or ligamentous injuries other
than ACL, and no studies measuring gastrocnemius, soleus
or popliteus muscles for any of the injuries.
We consistently found quadriceps and hamstring strength
deﬁcits in the ACL injured group both in the short- and
long-term. Increasing muscle strength is a primary focus of
rehabilitation guidelines [86–88]; however, impairments are
evident despite these eﬀorts. We also found that quadriceps
voluntary activation deﬁcits are evident in the short-term and
do not recover in the long-term, providing a potential under-
lying neural mechanism of the quadriceps muscle weakness.
This neural dysfunction, often described as arthrogenic
muscle inhibition (AMI), is hypothesised to be a protective
mechanism to avoid further joint damage following knee
injuries . However, it can be problematic if not restored
through rehabilitation, which would appear to be the case for
most of the participants measured in the included studies. We
could not control for the eﬀects of rehabilitation received
post-injury and, therefore, cannot comment on whether AMI
persistence is mediated by the appropriateness of a particular
rehabilitation approach. A recent scoping review suggested
the use of cryotherapy and exercise in the management of
AMI, albeit partly based on experimentally induced AMI
in healthy knees . It was also shown that after ACLR,
a 2-week rehabilitation programme including cryotherapy
application and physical exercise together improves AMI
more than cryotherapy or exercise alone . Currently,
exercise treatment is accepted as common practice [86–88],
and our meta-analysis of 14 studies (Fig.6) showed a lack
of activation deﬁcit resolution in the long-term, suggest-
ing either the rehabilitation approaches undertaken by the
recruited participants in the included studies were insuﬃcient
for resolving these deﬁcits, adherence was sub-optimal or
the implementation of rehabilitation strategies were lacking.
Quadriceps muscle strength and voluntary activation
deﬁcits were evident at the time return to sport commonly
occurs (i.e. 6–12months post-injury/surgery). Current
rehabilitation and return to sport guidelines recommend a
limb symmetry index threshold of 85–90% as a criterion
for strength recovery [86–88, 92, 93]. However, the pres-
ence of neuromuscular alterations in the contralateral limb
Fig. 3 Findings and literature gap map for meniscus studies. Colours
represent the evidence level as by van Tulder etal.  and direc-
tions represent injured group data when compared to control, with the
eﬀect size. SMD standardised mean diﬀerence, ST semitendinosus,
BF biceps femoris, Ham:Quad hamstring:quadriceps
Fig. 4 Forest plot of quadriceps active motor threshold from anterior cruciate ligament studies (increased active motor threshold meaning
decreased cortical excitability)
330 B.Tayfur et al.
Fig. 5 Forest plot of quadriceps Hoﬀman reﬂex (spinal excitability) from anterior cruciate ligament studies
Fig. 6 Forest plot of quadriceps voluntary activation from anterior cruciate ligament studies
Neuromuscular Function Following Knee Injuries: Does It Ever Get Back to Normal?
may cause overestimation of the injured-limb function [30,
31]. As such, use of symmetry-based strength outcomes
may reduce the ability to detect the strength deﬁcits we
found in this systematic review, as we did not accept con-
tralateral knee as a control group. It may be that identiﬁca-
tion of normative ranges from future research would better
inform return-to-play decisions.
We aimed to understand the nature of relevant central
and peripheral nervous system changes, including cortical
and spinal-reﬂexive pathways and found that these change
with time. We found no change in cortical excitability or in
spinal-reﬂex excitability in the short-term, with moderate
evidence. Short-term swelling and pain may be present
following knee injury/surgery, which does not aﬀect corti-
cal excitability but decreases spinal-reﬂex excitability [94,
95]. Experimental joint eﬀusion studies have also shown
that eﬀusion decreases spinal-reﬂex excitability immedi-
ately after injection [96, 97]. Therefore, the observed acute
unaﬀected values of spinal-reﬂex excitability may be due
to both swelling and pain shadowing an increased spinal
reﬂex excitability in the short-term.
In the longer term, there is strong evidence of decreased
cortical excitability and increased spinal-reflex excit-
ability, suggesting that neuromodulation of quadriceps
activation adapts and changes through time after injury/
surgery. Decreased cortical excitability means that knee-
injured patients need more stimulation to yield suﬃcient
excitation in the primary motor cortex to generate mus-
cle activation . While the clinical importance of these
changes in corticospinal and spinal-reﬂexive pathways is
not fully understood, recently it has been shown that cor-
ticospinal adaptations are correlated with muscle strength
and patient-reported knee function satisfaction following
ACLR . It may be that the decrease in cortical excit-
ability is a protective long-term motor cortex adapta-
tion, while a compensatory reﬂex mechanism maintains
required muscle function when needed i.e. as a preparatory
mechanism to avoid a sudden collapse of the knee joint in
knee-injured patients . It has been suggested that elec-
tromyographic biofeedback, transcranial magnetic stimula-
tion or transcutaneous electrical nerve stimulation may be
beneﬁcial in changing neural pathways to improve muscle
function ; however, empirical data are lacking to sup-
port these recommendations . Further studies exploring
the eﬀects of diﬀerent interventions on neuromodulation
of quadriceps may be helpful to understand the clinical
usefulness of these, or novel, modalities and approaches.
Meniscus injury caused heterogeneity and showed better
long-term outcomes when compared to ACL studies. Altered
sensory function is reported following ACL injuries and has
been hypothesised to be the cause of alterations in motor
response . Our results provide enough evidence to sup-
port that these changes in neuromuscular function are seen
in ACL-injured patients. However, it should be noted that
included studies were not investigating only isolated ACL
injury eﬀects as many of the ACL-injured participants had
a concomitant meniscal injury. Due to a lack of reporting
in most studies, we could not pool or detail the diﬀerences
between isolated ACL injuries vs those with concomitant
meniscus damage. There is evidence that combined injuries
may increase PTOA development risk when compared to iso-
lated ACL injuries [103, 104]; however, from the neuromus-
cular perspective, no diﬀerence was reported in quadriceps
strength or voluntary activation for isolated ACL injuries vs
ACL injuries with concomitant meniscus injury . There-
fore, neuromuscular alterations, mediated through quadriceps
weakness, may not be a critical pathway towards PTOA onset
in patients with isolated meniscus injuries, although the num-
ber of studies included in this study was insuﬃcient to draw a
conclusion. We speculate that our ﬁndings show preliminary
data supporting injury-speciﬁc changes, and should stimulate
further investigation in injury-speciﬁc groups, perhaps group-
ing injuries into cogent sub-groups.
There is a decreased rate of quadriceps torque develop-
ment, albeit with limited evidence, which would limit rapid
force production in knee-injured populations [106, 107].
This may be due to an increased neural processing time or
a delay in the transmission of force within the muscle and/
or tendon [108, 109]. Rapid force production may be more
relevant to daily life activities and sports than maximum
strength, as most of these activities require a quick muscle
response [106, 107]. Rapid force production is also corre-
lated with self-reported knee function  and functional
performance , and may not recover even if maximum
peak torque is regained . Therefore, the rate of torque
development may be an important descriptor of muscle func-
tion and further attention should be given to strengthen the
evidence and clarify the clinical relevance.
There is moderate evidence that quadriceps torque vari-
ability increases in the long-term, suggesting muscle control
impairments. Precise control of movement is essential for
optimal knee function, and insuﬃciency may cause altera-
tions in joint loading which may, in turn, lead to degenera-
tive cartilage changes . Increased torque variability is
also evident in knee OA patients ; thus, we speculate
that motor control of the quadriceps muscle may be another
component of neuromuscular alterations in the long-term
following injury/surgery potentially contributing to the ini-
tiation of knee OA.
We found an important evidence gap in the literature
concerning the change of muscle morphology. Our search
yielded several studies on muscle size; however, they either
did not include a suitable control group or were of low qual-
ity; due to procedural and reporting issues rather than the
absence of valid measurement tools. Only one moderate
quality study, providing very limited evidence, found no
332 B.Tayfur et al.
diﬀerence in quadriceps muscle volume in the long-term.
However, it has been reported that both neural alterations
and muscle size can predict up to 60% of the variance in
muscle strength post-injury . Muscle atrophy may
also explain strength deﬁcits more than activation failure
. Muscle size may have played an important role in
the strength deﬁcits found in this systematic review; there-
fore, future studies should consider measuring muscle size
in knee-injured populations together with other neuromus-
Future research is needed to improve our understanding
of neuromuscular changes post-injury, with morphological
and neural alterations being measured in the same knee-
injured populations to understand their interactions and
eﬀects on muscle strength, as well as muscle control and
the timing of movement generation. Another future step
should be understanding the impact of these neuromuscu-
lar alterations on movement patterns and joint loading, and
therefore their potential implications for PTOA onset. We
suggest including structural measurement of OA presence
in knee-injured populations to understand possible asso-
ciations of neuromuscular alterations with OA presence. A
clear association would further inform prospective studies to
determine whether these associations are causal.
Despite the increasing number of publications, and
accepted functional importance , we still do not have
strong evidence for key short- and long-term neuromuscu-
lar outcomes post-injury. The main research focus has been
on muscle strength, while the underlying neural mechanism
or morphological changes within the muscle have been of
less interest. More data are required to determine changes
in neuromuscular outcomes such as muscle size, timing of
Fig. 7 Forest plot of quadriceps slow concentric strength from anterior cruciate ligament studies
Neuromuscular Function Following Knee Injuries: Does It Ever Get Back to Normal?
muscle force production (i.e. rate of torque development,
electromechanical delay) and force control (i.e. torque vari-
ability). While the importance of measuring these factors in
the quadriceps muscle, especially post-ACL injury, is well-
established, changes in other muscles are often neglected
and should be further investigated.
Understanding the eﬀects of diﬀerent interventions may
help the development of better rehabilitation protocols that
may address the persistent neuromuscular impairments we
have shown in our systematic review. Future studies should
consider repeated measurement of neuromuscular function
to better understand its relation to changes in the patient’s
reported outcome measures and function. Further, such
data may yield useful ﬁndings about the prognostic value of
neuromuscular functional measures, which could help guide
both optimised rehabilitation and detection of osteoarthri-
tis development, while explaining individual diﬀerences
in responses. Therefore, the eﬀects of novel rehabilitation
strategies that target neuromuscular alterations of the knee
joint in knee-injured populations should be investigated and
further implemented in rehabilitation protocols to improve
short- and long-term outcomes.
4.1 Limitations andConsiderations forFuture
Studies systematically lacked reporting of participant selec-
tion procedures, possibly resulting in a high level of partici-
pant selection bias (Table1). Included patients may be those
still having symptoms in the long-term, which may result in
an inﬂated alteration in the injured group. Ideally, recruit-
ment would be as close as possible to the index injury, with
long-term follow-up, so as to include those who cope well
Fig. 8 Forest plot of hamstring slow concentric strength from anterior cruciate ligament studies
334 B.Tayfur et al.
with injury as well as those who do not (i.e. a prospective
There is evidence of altered neuro-muscular function in
the lower limb being a risk factor for knee injury .
Therefore, we cannot assume that identiﬁed deﬁcits are
purely the result of the injury as they may have been predis-
posing factors to injury in the ﬁrst place.
Our search strategy included terms of all knee ligaments
(ACL, PCL, MCL, and LCL), meniscal injuries, cartilage
injuries and post-traumatic OA. However, our results only
showed studies on ACL-injured or meniscus-injured popula-
tions. We also found that knee injury was a source of hetero-
geneity in some of the outcomes; therefore, our ﬁndings may
be speciﬁc to ACL and meniscus injuries, and not applicable
to other injuries.
Another limitation was the heterogeneity of the included
patients in most studies. ACL-injured patients included in
the studies were mixed both in terms of concomitant injury,
‘copers’ vs ‘non-copers’, and graft type if surgery was per-
formed. Due to a lack of reporting and inadequate study
numbers, we could not draw any conclusions on the eﬀects
of concomitant injuries or diﬀerent surgeries (i.e. diﬀerent
grafts), or comparison of ‘copers’ with ‘non-copers’.
Time since injury/surgery was used to deﬁne the short-
and long-term changes and for grouping the studies to pool
the data. Many of the included studies were not strict in
their time since injury/surgery criteria; therefore, the vari-
ability was high. I.e. a study could include participants
with a time since injury/surgery from 6 to 60months, with
a median of 24months. We used the mean or median time
to deﬁne the time groups; therefore, some variability in
the data may be expected due to the heterogeneity of time
since injury/surgery ranges of the included participants.
4.2 Clinical Implications
Persistent deﬁcits found in our study may highlight pos-
sible failures in current post-injury treatment strategies.
We found that quadriceps strength, voluntary activation,
control and speed of muscle force generation and ham-
string strength are affected; therefore, targeting these
deﬁcits may improve functional outcomes of knee-injury
rehabilitation. We acknowledge that measuring most of the
neuromuscular outcomes reported in this study may not
be feasible in clinical practice (i.e. cortical excitability,
spinal reﬂexes, torque-related outcomes, etc.); however,
research shows clinically applicable rehabilitation strate-
gies may improve these outcomes. For example, strength
training alone may not be suﬃcient to improve neuromus-
cular function of the knee joint, if movement quality and
speed of force production are being overlooked. It has been
suggested that a training protocol including controlled
muscle contractions with low-loads may improve muscle
force control , and heavy- or explosive-type resist-
ance training , or sensorimotor training focusing on
postural stabilization  may improve the rate of torque
development. For strength recovery, cryotherapy combined
with physical exercise has been shown to be eﬀective in
reducing muscle inhibition in the short-term after injury
, while progressive strength training shows promising
results in the long-term . Implementing these diﬀer-
ent exercise types may improve neuromuscular function
of the knee joint, thus enhancing functional outcome post-
injury with repeated measures of neuromuscular function
potentially useful to determine intervention mechanisms
alongside clinical eﬀectiveness. Such information could
inform more detailed rules for return to physical activity/
sport criteria, such as including motor control and qual-
ity of movement as well as maximum force capacity of
muscles. The subsequent eﬀect on PTOA development or
re-injury rates would be key impact markers. It should be
noted that our ﬁndings are mainly based on ACL-injured
populations; therefore future studies may yield diﬀerent
results for diﬀerent injury types (i.e. injuries to the other
ligaments in the knee joint, meniscus or cartilage).
Our study enhances understanding of neuromuscular func-
tion of the knee joint following injuries and shows that neu-
ral and muscular alterations are common and persistent in
the short- and long-term after injury/surgery. Strength and
voluntary activation deﬁcits are accompanied by changes in
cortical and spinal excitability for ACL patients in both the
short- and long-term (moderate to strong evidence), as well
as deﬁcits in force control and rapid force production (very
limited to moderate evidence). Only strength was investi-
gated in patients with meniscus injuries and short-term deﬁ-
cits demonstrated. Our study facilitates clinical recognition
of these deﬁcits, and promotes future research to advance
rehabilitation strategies to target these alterations, ultimately
contributing to eﬀorts made to optimise clinical outcomes
following knee injury and/or surgery and minimise PTOA
development or re-injury.
Funding Postgraduate studies of Ms Beyza Tayfur were sponsored
by Turkish Ministry of National Education. The sponsors had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
Conflict of Interest Beyza Tayfur, Chedsada Charuphongsa, Dylan
Morrissey and Stuart Miller declare that they have no conﬂicts of in-
terest relevant to the content of this review.
Neuromuscular Function Following Knee Injuries: Does It Ever Get Back to Normal?
Ethics approval Not applicable.
Consent to participate Not applicable.
Consent for publication Not applicable.
Availability of data and material The data that support the ﬁndings of
this study are available on request from the corresponding author [BT].
Code availability Not applicable.
Author contributions Conception and design of the study: BT, DM and
SCM. Screening of the articles, data extraction, methodological quality
ratings and data analysis: BT and CC. First drafting of the manuscript:
BT. Critical revision of the manuscript: DM and SCM. All authors
approved the version to be published.
Open Access This article is licensed under a Creative Commons Attri-
bution 4.0 International License, which permits use, sharing, adapta-
tion, distribution and reproduction in any medium or format, as long
as you give appropriate credit to the original author(s) and the source,
provide a link to the Creative Commons licence, and indicate if changes
were made. The images or other third party material in this article are
included in the article’s Creative Commons licence, unless indicated
otherwise in a credit line to the material. If material is not included in
the article’s Creative Commons licence and your intended use is not
permitted by statutory regulation or exceeds the permitted use, you will
need to obtain permission directly from the copyright holder. To view a
copy of this licence, visit http://creat iveco mmons .org/licen ses/by/4.0/.
1. Muthuri SG, McWilliams DF, Doherty M, Zhang W. History of
knee injuries and knee osteoarthritis: a meta-analysis of obser-
vational studies. Osteoarthr Cartil. 2011;19:1286–93.
2. Poulsen E, Goncalves GH, Bricca A, Roos EM, Thorlund JB,
Juhl CB. Knee osteoarthritis risk is increased 4–6 fold after knee
injury - a systematic review and meta-analysis. Br J Sports Med.
3. Snoeker B, Turkiewicz A, Magnusson K, Frobell R, Yu D, Peat
G, etal. Risk of knee osteoarthritis after diﬀerent types of knee
injuries in young adults: a population-based cohort study. Br J
Sport Med. 2020;54:725–30.
4. Lie MM, Risberg MA, Storheim K, Engebretsen L, Øiestad BE.
What’s the rate of knee osteoarthritis 10 years after anterior cru-
ciate ligament injury? An updated systematic review. Br J Sports
5. Carbone A, Rodeo S. Review of current understanding of post-
traumatic osteoarthritis resulting from sports injuries. J Orthop
6. Brophy RH, Gray BL, Nunley RM, Barrack RL, Clohisy JC.
Total knee arthroplasty after previous knee surgery. J Bone Jt
Surg Am. 2014;96:801–5.
7. Little CB, Hunter DJ. Post-traumatic osteoarthritis: from mouse
models to clinical trials. Nat Rev Rheumatol. 2013;9:485–97.
8. Øiestad BE, Juhl CB, Eitzen I, Thorlund JB. Knee extensor mus-
cle weakness is a risk factor for development of knee osteoar-
thritis. A systematic review and meta-analysis. Osteoarthr Cartil.
9. Lepley AS, Gribble PA, Thomas AC, Tevald MA, Sohn DH, Piet-
rosimone BG. Quadriceps neural alterations in anterior cruciate
ligament reconstructed patients: a 6-month longitudinal investi-
gation. Scand J Med Sci Sports. 2015;25:828–39.
10. Harkey MS, Luc-Harkey BA, Lepley AS, Grindstaﬀ TL, Grib-
ble P, Blackburn JT, etal. Persistent muscle inhibition after
anterior cruciate ligament reconstruction. Med Sci Sport Exerc.
11. Larsen JB, Farup J, Lind M, Dalgas U. Muscle strength and func-
tional performance is markedly impaired at the recommended
time point for sport return after anterior cruciate ligament recon-
struction in recreational athletes. Hum Mov Sci. 2015;39:73–87.
12. Tengman E, Olofsson LB, Stensdotter AK, Nilsson KG, Häger
CK, Tengman E. Anterior cruciate ligament injury after more
than 20 years. II. Concentric and eccentric knee muscle strength.
Scand J Med Sci Sports. 2014;24:e501-509.
13. Lewek M, Rudolph K, Axe M, Snyder-Mackler L. The eﬀect of
insuﬃcient quadriceps strength on gait after anterior cruciate
ligament reconstruction. Clin Biomech. 2002;17:56–63.
14. Hart HF, Culvenor AG, Collins NJ, Ackland DC, Cowan
SM, Machotka Z, etal. Knee kinematics and joint moments
during gait following anterior cruciate ligament econstruc-
tion: a systematic review and meta-analysis. Br J Sports Med.
15. Andriacchi TP, Koo S, Scanlan SF. Gait mechanics inﬂuence
healthy cartilage morphology and osteoarthritis of the knee. J
Bone Jt Surg Am. 2009;91:95–101.
16. Whittaker JL, Roos EM. A pragmatic approach to prevent post-
traumatic osteoarthritis after sport or exercise-related joint injury.
Best Pract Res Clin Rheumatol. 2019;33:158–71.
17. Allen KD, Choong PF, Davis AM, Dowsey MM, Dziedzic KS,
Emery C, etal. Osteoarthritis: Models for appropriate care
across the disease continuum. Best Pract Res Clin Rheumatol.
18. Karanikas K, Arampatzis A, Brüggemann GP. Motor task and
muscle strength followed diﬀerent adaptation patterns after ante-
rior cruciate ligament reconstruction. Eur J Phys Rehabil Med.
19. Hart JM, Pietrosimone B, Hertel J, Ingersoll CD. Quadriceps
activation following knee injuries: a systematic review. J Athl
20. Kuenze CM, Hertel J, Weltman A, Diduch D, Saliba SA, Hart
JM. Persistent neuromuscular and corticomotor quadriceps asym-
metry after anterior cruciate ligament reconstruction. J Athl
21. Wieschhoﬀ GG, Mandell JC, Czuczman GJ, Nikac V, Shah N,
Smith SE. Acute non-contact anterior cruciate ligament tears are
associated with relatively increased vastus medialis to semimem-
branosus cross-sectional area ratio: a case-control retrospective
MR study. Skeletal Radiol. 2017;46:1469–75.
22. Pamukoﬀ DN, Pietrosimone BG, Ryan ED, Lee DR, Black-
burn JT. Quadriceps function and hamstrings co-activation
after anterior cruciate ligament reconstruction. J Athl Train.
23. Vairo GL, Myers JB, Sell TC, Fu FH, Harner CD, Lephart SM.
Neuromuscular and biomechanical landing performance subse-
quent to ipsilateral semitendinosus and gracilis autograft anterior
cruciate ligament reconstruction. Knee Surg Sport Traumatol
24. Sasaki K, Neptune RR. Individual muscle contributions to the
axial knee joint contact force during normal walking. J Biomech.
25. Petersen W, Taheri P, Forkel P, Zantop T. Return to play fol-
lowing ACL reconstruction: a systematic review about strength
deﬁcits. Arch Orthop Trauma Surg. 2014;134:1417–28.
26. Lisee C, Lepley AS, Birchmeier T, O’Hagan K, Kuenze C.
Quadriceps strength and volitional activation after anterior
336 B.Tayfur et al.
cruciate ligament reconstruction: a systematic review and meta-
analysis. Sport Health. 2019;11:163–79.
27. Hall M, Juhl CB, Lund H, Thorlund JB. Knee extensor mus-
cle strength in middle-aged and older individuals undergoing
arthroscopic partial meniscectomy: a systematic review and
meta-analysis. Arthritis Care Res. 2015;67:1289–96.
28. Xergia SA, Mcclelland JA, Kvist J, Vasiliadis HS, Georgoulis
AD. The inﬂuence of graft choice on isokinetic muscle strength
4–24 months after anterior cruciate ligament reconstruction.
Knee Surg Sport Traumatol Arthrosc. 2011;5:768–80.
29. Van Meer BL, Oei EHG, Meuﬀels DE, Van Arkel ERA, Verhaar
JAN, Bierma-Zeinstra SMA, etal. Degenerative changes in the
knee 2 years after anterior cruciate ligament rupture and related
risk factors: a prospective observational follow-up study. Am J
Sports Med. 2016;44:1524–33.
30. Mirkov DM, Knezevic OM, Maﬃuletti NA, Kadija M, Nedeljko-
vic A, Jaric S. Contralateral limb deﬁcit after ACL-reconstruc-
tion: an analysis of early and late phase of rate of force develop-
ment. J Sports Sci. 2017;35:435–40.
31. Hiemstra LA, Webber S, MacDonald PB, Kriellaars DJ. Con-
tralateral limb strength deﬁcits after anterior cruciate ligament
reconstruction using a hamstring tendon graft. Clin Biomech.
32. Moher D, Liberati A, Tetzlaﬀ J, Altman DG. Preferred reporting
items for systematic reviews and meta-analyses: the PRISMA
statement. Ann Intern Med. 2009;151:264.
33. Downs SH, Black N. The feasibility of creating a checklist for the
assessment of the methodological quality both of randomised and
non-randomised studies of health care interventions. J Epidemiol
Community Health. 1998;52:377–84.
34. Deasy M, Leahy E, Semciw AI. Hip strength deﬁcits in people
with symptomatic knee osteoarthritis: a systematic review with
meta-analysis. J Orthop Sport Phys Ther. 2016;46:629–39.
35. Munn J, Sullivan SJ, Schneiders AG. Evidence of sensorimotor
deﬁcits in functional ankle instability: a systematic review with
meta-analysis. J Sci Med Sport. 2010;13:2–12.
36. Zhang Z, Xu X, Ni H. Small studies may overestimate the eﬀect
sizes in critical care meta-analyses: a meta-epidemiological
study. Crit Care. 2013;17:R2.
37. Sterne JA, Egger M, Smith GD. Systematic reviews in health
care: Investigating and dealing with publication and other biases
in meta-analysis. BMJ. 2001;323:101–5.
38. Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring
inconsistency in meta-analyses. BMJ. 2003;327:557–60.
39. Cohen J. Statistical power analysis for the behavioral sciences.
2nd ed. Cambridge: Academic press; 2013.
40. van Tulder M, Furlan A, Bombardier C, Bouter L, Editorial Board
of the Cochrane Collaboration Back Review Group. Updated
method guidelines for systematic reviews in the Cochrane col-
laboration back review group. Spine. 2003;28:1290–9.
41. de Almeida AM, Santos Silva PR, Pedrinelli A, Hernandez AJ.
Aerobic ﬁtness in professional soccer players after anterior cruci-
ate ligament reconstruction. PLoS ONE. 2018;13:e0194432.
42. Chung KS, Ha JK, Yeom CH, Ra HJ, Lim JW, Kwon MS, etal.
Are muscle strength and function of the uninjured lower limb
weakened after anterior cruciate ligament injury? Am J Sports
43. Clagg S, Paterno MV, Hewett TE, Schmitt LC. Performance
on the modiﬁed star excursion balance test at the time of return
to sport following anterior cruciate ligament reconstruction. J
Orthop Sports Phys Ther. 2015;45:444–52.
44. Engelen-van Melick N, van Cingel REH, van Tienen TG,
Nijhuis-van der Sanden MWG. Functional performance
2–9 years after ACL reconstruction: cross-sectional com-
parison between athletes with bone–patellar tendon–bone,
semitendinosus/gracilis and healthy controls. Knee Surg Sport
Traumatol Arthrosc. 2017;25:1412–23.
45. Freddolini M, Battaglioli A, Chiechi F, Placella G, Georgoulis
A, Cerulli G, etal. Electromechanical delay of the knee ﬂexor
muscles after anterior cruciate ligament reconstruction using
semitendinosus tendon. Sport Biomech. 2015;14:384–93.
46. Garrison JC, Hannon J, Goto S, Giesler L, Bush C, Both-
well JM. Participants at three months post-operative anterior
cruciate ligament reconstruction (ACL-R) demonstrate dif-
ferences in lower extremity energy absorption contribution
and quadriceps strength compared to healthy controls. Knee.
47. Goetschius J, Hart JM. Knee-extension torque variability and
subjective knee function in patients with a history of anterior
cruciate ligament reconstruction. J Athl Train. 2016;51:22–7.
48. Goetschius J, Hertel J, Saliba S, Brockmeier SF, Hart JM. The
eﬀects of patellar tendon vibration on quadriceps strength in
anterior cruciate ligament reconstructed knees. Phys Ther Sport.
49. Hall M, Wrigley TV, Metcalf BR, Hinman RS, Dempsey AR,
Mills PM, etal. A longitudinal study of strength and gait after
arthroscopic partial meniscectomy. Med Sci Sport Exerc.
50. Holsgaard-Larsen A, Jensen C, Mortensen NHM, Aagaard P.
Concurrent assessments of lower limb loading patterns, mechani-
cal muscle strength and functional performance in ACL-patients
— a cross-sectional study. Knee. 2014;21:66–73.
51. Hsiao S-F, Chou P-H, Hsu H-C, Lue Y-J. Changes of muscle
mechanics associated with anterior cruciate ligament deﬁciency
and reconstruction. J Strength Cond Res. 2014;28:390–400.
52. Hsieh C-J, Indelicato PA, Moser MW, Vandenborne K,
Chmielewski TL. Speed, not magnitude, of knee extensor torque
production is associated with self-reported knee function early
after anterior cruciate ligament reconstruction. Knee Surg Sport
Traumatol Arthrosc. 2015;23:3214–20.
53. Ilich SS, Dempsey AR, Mills PM, Sturnieks DL, Stachowiak
GW, Maguire KF, etal. Physical activity patterns and function 3
months after arthroscopic partial meniscectomy. J Sci Med Sport.
54. Johnson AK, Palmieri-Smith RM, Lepley LK. Contribution of
neuromuscular factors to quadriceps asymmetry after anterior
cruciate ligament reconstruction. J Athl Train. 2018;53:347–54.
55. Kaminska E, Piontek T, Wiernicka M, Cywinska-Wasilewska
G, Lewandowski J, Lochynski D. Differences in isokinetic
strength of the knee extensors and ﬂexors in men with isolated
and combined cruciate-ligament knee injury. J Sport Rehabil.
56. Kellis E, Galanis N, Kofotolis N. Hamstring-to-quadriceps ratio
in female athletes with a previous hamstring injury, anterior cru-
ciate ligament reconstruction, and controls. Sports. 2019;7:214.
57. Kline PW, Burnham J, Yonz M, Johnson D, Ireland ML, Noehren
B. Hip external rotation strength predicts hop performance after
anterior cruciate ligament reconstruction. Knee Surg Sport Trau-
matol Arthrosc. 2018;26:1137–44.
58. Krishnan C, Williams GN. Factors explaining chronic knee
extensor strength deﬁcits after ACL reconstruction. J Orthop
59. Kuenze CM, Kelly AR, Jun H-P, Eltoukhy M. Unilateral quadri-
ceps strengthening with disinhibitory cryotherapy and quadriceps
symmetry after anterior cruciate ligament reconstruction. J Athl
60. Kvist J, Karlberg C, Gerdle B, Gillquist J. Anterior tibial transla-
tion during diﬀerent isokinetic quadriceps torque in anterior cru-
ciate ligament deﬁcient and nonimpaired individuals. J Orthop
Sport Phys Ther. 2001;31:4–15.
Neuromuscular Function Following Knee Injuries: Does It Ever Get Back to Normal?
61. Lepley AS, Ericksen HM, Sohn DH, Pietrosimone BG. Contribu-
tions of neural excitability and voluntary activation to quadriceps
muscle strength following anterior cruciate ligament reconstruc-
tion. Knee. 2014;21:736–42.
62. Lepley AS, Grooms DR, Burland JP, Davi SM, Kinsella-Shaw
JM, Lepley LK. Quadriceps muscle function following ante-
rior cruciate ligament reconstruction: systemic differences
in neural and morphological characteristics. Exp Brain Res.
63. Maeda N, Urabe Y, Tsutsumi S, Fujishita H, Numano S, Takeuchi
T, etal. Symmetry tensiomyographic neuromuscular response
after chronic anterior cruciate ligament (ACL) reconstruction.
Knee Surg Sport Traumatol Arthrosc. 2018;26:411–7.
64. Norte GE, Hertel J, Saliba SA, Diduch DR, Hart JM. Quadri-
ceps neuromuscular function in patients with anterior cruciate
ligament reconstruction with or without knee osteoarthritis: a
cross-sectional study. J Athl Train. 2018;53:475–85.
65. Oeﬃnger DJ, Shapiro R, Nyland J, Pienkowski D, Caborn DNM.
Delayed gastrocnemius muscle response to sudden perturbation
in rehabilitated patients with anterior cruciate ligament recon-
struction. Knee Surg Sport Traumatol Arthrosc. 2001;9:19–27.
66. O’Malley E, Richter C, King E, Strike S, Moran K, Franklyn-
Miller A, etal. Countermovement jump and isokinetic dynamom-
etry as measures of rehabilitation status after anterior cruciate
ligament reconstruction. J Athl Train. 2018;53:687–95.
67. Pamukoﬀ DN, Montgomery MM, Choe KH, Moﬃt TJ, Garcia
SA, Vakula MN. Bilateral alterations in running mechanics and
quadriceps function following unilateral anterior cruciate liga-
ment reconstruction. J Orthop Sports Phys Ther. 2018;48:960–7.
68. Reed-Jones RJ, Vallis LA. Kinematics and muscular
responses to a ramp descent in the ACL deﬁcient knee. Knee.
69. Ristanis S, Tsepis E, Giotis D, Stergiou N, Cerulli G, Georgou-
lis AD. Electromechanical delay of the knee ﬂexor muscles is
impaired after harvesting hamstring tendons for anterior cruciate
ligament reconstruction. Am J Sports Med. 2009;37:2179–86.
70. Roos PE, Button K, van Deursen RWM. Motor control strate-
gies during double leg squat following anterior cruciate ligament
rupture and reconstruction: an observational study. J Neuroeng
71. Scheurer SA, Sherman DA, Glaviano NR, Ingersoll CD, Norte
GE. Corticomotor function is associated with quadriceps rate of
torque development in individuals with ACL surgery. Exp Brain
72. Sturnieks DL, Besier TF, Hamer PW, Ackland TR, Mills PM,
Stachowiak GW, etal. Knee strength and knee adduction
moments following arthroscopic partial meniscectomy. Med Sci
Sport Exerc. 2008;40:991–7.
73. Thomas AC, Lepley LK, Wojtys EM, McLean SG, Palmieri-
Smith RM. Effects of neuromuscular fatigue on quadriceps
strength and activation and knee biomechanics in individu-
als post–anterior cruciate ligament reconstruction and healthy
adults. J Orthop Sport Phys Ther. 2015;45:1042–50.
74. Thorlund JB, Aagaard P, Roos EM. Thigh muscle strength,
functional capacity, and self-reported function in patients at
high risk of knee osteoarthritis compared with controls. Arthri-
tis Care Res. 2010;62:1244–51.
75. Thorlund JB, Aagaard P, Roos EM. Muscle strength and func-
tional performance in patients at high risk of knee osteoarthri-
tis: a follow-up study. Knee Surg Sport Traumatol Arthrosc.
76. Tourville TW, Jarrell KM, Naud S, Slauterbeck JR, Johnson
RJ, Beynnon BD. Relationship between isokinetic strength and
tibiofemoral joint space width changes after anterior cruciate
ligament reconstruction. Am J Sports Med. 2014;42:302–11.
77. Tsarouhas A, Giakas G, Malizos KN, Spiropoulos G, Sideris
V, Koutedakis Y, etal. Dynamic eﬀect of quadriceps mus-
cle activation on anterior tibial translation after single-bundle
and double-bundle anterior cruciate ligament reconstruction.
Arthrosc J Arthrosc Relat Surg. 2015;31:1303–9.
78. Vairo GL. Knee ﬂexor strength and endurance proﬁles after
ipsilateral hamstring tendons anterior cruciate ligament recon-
struction. Arch Phys Med Rehabil. 2014;95:552–61.
79. Vairo GL, Miller SJ, Sherbondy PS, Sebastianelli WJ, Buckley
WE. Standing ﬂexion deﬁcits predict self-reported outcomes
in women after ipsilateral hamstring anterior cruciate ligament
reconstruction. Arthroscopy. 2013;29:1796–803.
80. Ward SH, Perraton L, Bennell K, Pietrosimone B, Bryant AL.
Deﬁcits in quadriceps force control after anterior cruciate
ligament injury: potential central mechanisms. J Athl Train.
81. Welling W, Benjaminse A, Lemmink K, Dingenen B, Gokeler
A. Progressive strength training restores quadriceps and
hamstring muscle strength within 7 months after ACL recon-
struction in amateur male soccer players. Phys Ther Sport.
82. Xergia SA, Pappas E, Zampeli F, Georgiou S, Georgoulis AD.
Asymmetries in functional hop tests, lower extremity kinematics,
and isokinetic strength persist 6 to 9 months following anterior
cruciate ligament reconstruction. J Orthop Sports Phys Ther.
83. Zarzycki R, Morton SM, Charalambous CC, Marmon A, Sny-
der-Mackler L. Corticospinal and intracortical excitability dif-
fer between athletes early after ACLR and matched controls. J
Orthop Res. 2018;36:2941–8.
84. Zult T, Gokeler A, van Raay JJAM, Brouwer RW, Zijdewind
I, Hortobágyi T. An anterior cruciate ligament injury does not
aﬀect the neuromuscular function of the non-injured leg except
for dynamic balance and voluntary quadriceps activation. Knee
Surg Sport Traumatol Arthrosc. 2017;25:172–83.
85. Zwolski C, Schmitt LC, Thomas S, Hewett TE, Paterno MV. The
utility of limb symmetry indices in return-to-sport assessment in
patients with bilateral anterior cruciate ligament reconstruction.
Am J Sports Med. 2016;44:2030–8.
86. Myer GD, Paterno MV, Ford KR, Quatman CE, Hewett TE.
Rehabilitation after anterior cruciate ligament reconstruction:
criteria-based progression through the return-to-sport phase. J
Orthop Sport Phys Ther. 2006;36:385–402.
87. van Melick N, van Cingel REH, Brooijmans F, Neeter C, van
Tienen T, Hullegie W, etal. Evidence-based clinical practice
update: practice guidelines for anterior cruciate ligament reha-
bilitation based on a systematic review and multidisciplinary
consensus. Br J Sports Med. 2016;50:1506–15.
88. Adams D, Logerstedt D, Hunter-Giordano A, Axe MJ, Snyder-
Mackler L. Current concepts for anterior cruciate ligament recon-
struction: a criterion-based rehabilitation progression. J Orthop
Sport Phys Ther. 2012;42:601–14.
89. Hopkins JT, Ingersoll CD. Arthrogenic muscle inhibition: a limit-
ing factor in joint rehabilitation. J Sport Rehabil. 2000;9:135–59.
90. Sonnery-Cottet B, Saithna A, Quelard B, Daggett M, Borade
A, Ouanezar H, etal. Arthrogenic muscle inhibition after ACL
reconstruction: a scoping review of the eﬃcacy of interventions.
Br J Sports Med. 2019;53:289–98.
91. Hart JM, Kuenze CM, Diduch DR, Ingersoll CD. Quadriceps
muscle function after rehabilitation with cryotherapy in patients
with anterior cruciate ligament reconstruction. J Athl Train.
92. Lynch AD, Logerstedt DS, Grindem H, Eitzen I, Hicks GE, Axe
MJ, etal. Consensus criteria for deﬁning “successful outcome”
after ACL injury and reconstruction: a Delaware-Oslo ACL
cohort investigation. Br J Sports Med. 2015;49:335–42.
338 B.Tayfur et al.
93. Filbay SR, Grindem H. Evidence-based recommendations for the
management of anterior cruciate ligament (ACL) rupture. Best
Pract Res Clin Rheumatol. 2019;33:33–47.
94. Hopkins JT, Ingersoll CD, Andrew Krause B, Edwards JE,
Cordova ML. Eﬀect of knee joint eﬀusion on quadriceps and
soleus motoneuron pool excitability. Med Sci Sports Exerc.
95. Park J, Hopkins JT. Induced anterior knee pain immediately
reduces involuntary and voluntary quadriceps activation. Clin J
Sport Med. 2013;23:19–24.
96. Palmieri RM, Tom JA, Edwards JE, Weltman A, Saliba EN, Mis-
try DJ, etal. Arthrogenic muscle response induced by an experi-
mental knee joint eﬀusion is mediated by pre- and post-synaptic
spinal mechanisms. J Electromyogr Kinesiol. 2004;14:631–40.
97. Hopkins JT, Ingersoll CD, Edwards JE, Cordova ML. Changes
in soleus motoneuron pool excitability after artiﬁcial knee joint
eﬀusion. Arch Phys Med Rehabil. 2000;81:1199–203.
98. Groppa S, Oliviero A, Eisen A, Quartarone A, Cohen LG, Mall
V, etal. A practical guide to diagnostic transcranial magnetic
stimulation: report of an IFCN committee. Clin Neurophysiol.
99. Bodkin SG, Norte GE, Hart JM. Corticospinal excitability can
discriminate quadriceps strength indicative of knee function after
ACL-reconstruction. Scand J Med Sci Sport. 2019;29:716–24.
100. Alkjaer T, Raﬀalt PC, Dalsgaard H, Simonsen EB, Petersen NC,
Bliddal H, etal. Gait variability and motor control in people with
knee osteoarthritis. Gait Posture. 2015;42:479–84.
101. Pietrosimone BG, McLeod MM, Lepley AS. A theoretical frame-
work for understanding neuromuscular response to lower extrem-
ity joint injury. Sport Health. 2012;4:31–5.
102. Relph N, Herrington L, Tyson S. The eﬀects of ACL injury
on knee proprioception: a meta-analysis. Physiotherapy.
103. Luc B, Gribble PA, Pietrosimone BG. Osteoarthritis prevalence
following anterior cruciate ligament reconstruction: a system-
atic review and numbers-needed-to-treat analysis. J Athl Train.
104. Risberg MA, Oiestad BE, Gunderson R, Aune AK, Engebretsen
L, Culvenor A, etal. Changes in knee osteoarthritis, symptoms,
and function after anterior cruciate ligament reconstruction. Am
J Sports Med. 2015;44:1215–24.
105. Lepley LK, Wojtys EM, Palmieri-Smith RM. Does concomitant
meniscectomy or meniscal repair aﬀect the recovery of quadri-
ceps function post-ACL reconstruction? Knee Surg Sport Trau-
matol Arthrosc. 2015;23:2756–61.
106. Aagaard P, Simonsen EB, Andersen JL, Magnusson P, Dyhre-
Poulsen P. Increased rate of force development and neural drive
of human skeletal muscle following resistance training. J Appl
107. Angelozzi M, Madama M, Corsica C, Calvisi V, Properzi G,
McCaw ST, etal. Rate of force development as an adjunctive
outcome measure for return-to-sport decisions after anterior
cruciate ligament reconstruction. J Orthop Sport Phys Ther.
108. Andersen LL, Aagaard P. Inﬂuence of maximal muscle strength
and intrinsic muscle contractile properties on contractile rate of
force development. Eur J Appl Physiol. 2006;96:46–52.
109. Kaneko F, Onari K, Kawaguchi K, Tsukisaka K, Roy SH. Elec-
tromechanical delay after ACL reconstruction: an innovative
method for investigating central and peripheral contributions. J
Orthop Sport Phys Ther. 2002;32:158–65.
110. Pääsuke M, Ereline J, Gapeyeva H. Knee extension strength and
vertical jumping performance in nordic combined athletes. J
Sports Med Phys Fit. 2001;41:354–61.
111. Andriacchi TP, Favre J. The nature of invivo mechanical signals
that inﬂuence cartilage health and progression to knee osteoar-
thritis. Curr Rheumatol Rep. 2014;16:463.
112. Hortobágyi T, Garry J, Holbert D, Devita P. Aberrations in the
control of quadriceps muscle force in patients with knee osteo-
arthritis. Arthritis Care Res. 2004;51:562–9.
113. Williams GN, Buchanan TS, Barrance PJ, Axe MJ, Snyder-Mack-
ler L. Quadriceps weakness, atrophy, and activation failure in
predicted noncopers after anterior cruciate ligament injury. Am
J Sports Med. 2005;33:402–7.
114. Thomas AC, Wojtys EM, Brandon C, Palmieri-Smith RM. Mus-
cle atrophy contributes to quadriceps weakness after anterior cru-
ciate ligament reconstruction. J Sci Med Sport. 2016;19:7–11.
115. Kambhampati SBS, Vaishya R. Trends in publications on the
anterior cruciate ligament over the past 40 years on PubMed.
Orthop J Sport Med. 2019;7:2325967119856883.
116. Smeets A, Malfait B, Dingenen B, Robinson MA, Vanrenterghem
J, Peers K, etal. Is knee neuromuscular activity related to
anterior cruciate ligament injury risk? A pilot study. Knee.
117. Kobayashi H, Koyama Y, Enoka RM, Suzuki S. A unique form
of light-load training improves steadiness and performance on
some functional tasks in older adults. Scand J Med Sci Sports.
118. Gruber M, Gollhofer A. Impact of sensorimotor training on
the rate of force development and neural activation. Eur J Appl
Terms and Conditions
Springer Nature journal content, brought to you courtesy of Springer Nature Customer Service Center GmbH (“Springer Nature”).
Springer Nature supports a reasonable amount of sharing of research papers by authors, subscribers and authorised users (“Users”), for small-
scale personal, non-commercial use provided that all copyright, trade and service marks and other proprietary notices are maintained. By
purposes, Springer Nature considers academic use (by researchers and students) to be non-commercial.
These Terms are supplementary and will apply in addition to any applicable website terms and conditions, a relevant site licence or a personal
subscription. These Terms will prevail over any conflict or ambiguity with regards to the relevant terms, a site licence or a personal subscription
(to the extent of the conflict or ambiguity only). For Creative Commons-licensed articles, the terms of the Creative Commons license used will
We collect and use personal data to provide access to the Springer Nature journal content. We may also use these personal data internally within
ResearchGate and Springer Nature and as agreed share it, in an anonymised way, for purposes of tracking, analysis and reporting. We will not
otherwise disclose your personal data outside the ResearchGate or the Springer Nature group of companies unless we have your permission as
While Users may use the Springer Nature journal content for small scale, personal non-commercial use, it is important to note that Users may
use such content for the purpose of providing other users with access on a regular or large scale basis or as a means to circumvent access
use such content where to do so would be considered a criminal or statutory offence in any jurisdiction, or gives rise to civil liability, or is
falsely or misleadingly imply or suggest endorsement, approval , sponsorship, or association unless explicitly agreed to by Springer Nature in
use bots or other automated methods to access the content or redirect messages
override any security feature or exclusionary protocol; or
share the content in order to create substitute for Springer Nature products or services or a systematic database of Springer Nature journal
In line with the restriction against commercial use, Springer Nature does not permit the creation of a product or service that creates revenue,
royalties, rent or income from our content or its inclusion as part of a paid for service or for other commercial gain. Springer Nature journal
content cannot be used for inter-library loans and librarians may not upload Springer Nature journal content on a large scale into their, or any
other, institutional repository.
content on this website and may remove it or features or functionality at our sole discretion, at any time with or without notice. Springer Nature
may revoke this licence to you at any time and remove access to any copies of the Springer Nature journal content which have been saved.
To the fullest extent permitted by law, Springer Nature makes no warranties, representations or guarantees to Users, either express or implied
with respect to the Springer nature journal content and all parties disclaim and waive any implied warranties or warranties imposed by law,
including merchantability or fitness for any particular purpose.
Please note that these rights do not automatically extend to content, data or other material published by Springer Nature that may be licensed
from third parties.
If you would like to use or distribute our Springer Nature journal content to a wider audience or on a regular basis or in any other manner not
expressly permitted by these Terms, please contact Springer Nature at