Interventions for treating injuries of the medial ligaments of the knee

  • Protocol
  • Intervention

Authors


Abstract

This is the protocol for a review and there is no abstract. The objectives are as follows:

To assess the effects (benefits and harms) of interventions for treating injuries to the medial ligaments of the knee. We intend to compare different types of conservative intervention (e.g. no bracing versus bracing), surgical versus conservative intervention, different surgical interventions (e.g. reconstruction versus repair) and early post-operative treatments.

Background

Description of the condition

The medial knee ligaments are found on the inwards facing side of the knee joint. These connect the femur (thigh bone) to the tibia (shinbone) and, together with the lateral (outwards facing) ligaments found on the other side of the knee, help control the sideways motion of the knee joint. The medial ligaments comprise three main ligaments: the superficial medial collateral ligament (MCL), the deep MCL and the posterior oblique ligament (POL), which is part of the posteromedial complex (PMC) of the knee. The superficial MCL is the main restraint against valgus knee instability (gaping open of the inner aspect of the knee joint), whereas the POL and deep MCL provide secondary restraints against valgus loads (forces directed towards the inner (or midline) aspect of the knee) and are also important restraints to internal and external rotational forces (forces that move the leg position so that the foot is turned inwards or outwards, respectively) (Coobs 2010). The PMC stabilises the knee in extension, and contributes one-third of the restraint of the knee to valgus loads with the knee in extension. The medial knee ligaments are among the most commonly injured ligaments of the knee (Phisitkul 2006). Injuries to the medial knee ligaments are most common in young people during sporting activities, have an annual incidence of 0.24 per 1000 and occur more often in males (2:1 male to female ratio) (Daniel 2003; Wijdicks 2010). These injuries also occur frequently in skeletally immature persons.

Medial ligament injuries usually occur after direct impact to the lateral, or outer, aspect of the knee, thigh or leg while the foot is planted on the ground. This results in a direct valgus stress (in relative terms, the foot moves away from the midline, while the knee joint is forced towards the midline) to the knee joint and is the most common mechanism of this injury amongst contact athletes. The medial knee ligaments can also be injured without direct trauma if a valgus knee stress (forcing the knee inwards) occurs together with tibial external rotation, that is, the position of the leg is rotated so that the foot is pointing outwards (Marchant 2011). This pattern of injury is more frequent during pivoting activities in sports such as skiing, basketball and football. If either mechanism of injury occurs with high energy, a more complex ligamentous knee injury can occur that may also involve either the anterior cruciate ligament (ACL) or posterior cruciate ligament (PCL), or both (Harner 2004). These two cruciate ligaments, which are arranged as a cross in the centre of the knee joint, provide stability while permitting a large range of movement.

The most established clinical classification for medial knee ligament injuries is the American Medical Association Standard Nomenclature of Athletic Injuries system (American Medical Association 1966) that utilises valgus stress-testing to define the severity of injury. This classification system has since been modified to include also an assessment of laxity (Hughston 1994). Grade I injuries demonstrate localised tenderness with no instability and result from microscopic tears to the superficial MCL or deep MCL; grade II injuries show more generalised tenderness but still no instability and represent incomplete but gross tears of the superficial MCL or deep MCL; and grade III injuries exhibit instability on valgus stress-testing representing complete disruption of medial knee ligaments. Grade III injuries can be sub-classified by their degree of laxity on applying a valgus stress (performed with the knee at 30° of flexion) with 1+, 2+ and 3+ subtypes assigned to 3 to 5 mm, 6 to 10 mm and > 10 mm medial joint opening, respectively, compared with the knee joint of the uninjured, opposite lower limb.

This grading system can help determine injury severity and treatment decisions and inform long-term prognosis. Grade I and II medial knee ligament injuries may lead to reduced knee function and preliminary osteoarthritic joint changes at long-term follow-up (Lundberg 1996), and patients with isolated grade III injuries often progress to develop chronic joint laxity and early osteoarthritis (Kannus 1988; Reider 1994). Most people sustaining grade I injuries experience minimal symptoms and do not seek medical consultation, whereas grade II and III injuries each comprise 48% of those patients who do present for medical assessment (Grant 2012). Further ligamentous injuries are identified in 78% of grade III injuries; ACL disruption is the most frequent concurrent ligamentous injury (Fetto 1978). Patients with combined MCL and ACL injuries also commonly have POL ruptures, with 35% having ruptured the entire PMC (Halinen 2006).

A second commonly used classification system for injuries to the medial ligaments of the knee was described by Fetto and Marshall (Fetto 1978). In this classification system, grade I injuries are those with no valgus instability at both 0 and 30 degrees of knee flexion; grade II injuries are those stable at 0 degrees of knee flexion, but with valgus instability at 30 degrees of knee flexion; and grade III injuries are those with valgus instability at both 0 and 30 degrees of knee flexion. This classification system is simple to apply during clinical examination and it can identify the instability from disruption of all medial structures of the knee, which may inform the treatment strategy. Magnetic resonance imaging can also assist treatment decisions by determining the anatomic location of the injuries to the medial knee ligaments.

Description of the intervention

Several treatment options exist for injuries to the medial ligaments of the knee. Less severe injuries are generally treated conservatively (non-surgically), and more severe injuries are considered for surgical intervention. Initial conservative therapy generally involves rest, ice, compression and elevation. Use of a controlled motion knee brace for approximately six weeks (to permit protected knee motion) and a functional rehabilitation programme is typical non-surgical treatment for isolated incomplete tears and select complete tears of the medial knee ligaments (Holden 1983; Petermann 1993).

Surgical treatment of medial ligament injuries may involve acute repair of selected isolated complete tears, or delayed repair of acute injuries if further concurrent ligament injuries are best managed by being allowed to heal first (Phisitkul 2006). Surgical repair may involve direct repair of injured or ruptured ligaments or reconstruction with autograft (harvest of tissue (often a tendon) from the patient) or allograft (harvest of tissue from a donor patient) material, or synthetic grafts. Post-operative physiotherapy is usually tailored to the extent of the injury and surgical repair, but generally involves controlled motion bracing and a period of restricted weight-bearing.

How the intervention might work

The choice of intervention used to treat injuries to the medial ligaments of the knee will depend on the severity of the injury, the magnitude of joint laxity, and whether or not there are combined ligamentous injuries. Healing of the injured medial ligament complex progresses through the classic stages of haemorrhage, inflammation, repair and remodelling, and the capacity of these ligaments to heal is influenced by the location and extent of the injury (Frank 1995). For microscopic and incomplete injuries to the medial knee ligaments, conservative management may involve staged progression of both mobilisation and weight-bearing by the affected knee joint, and use of supportive braces during the direct healing process. Though bracing and protected weight-bearing are traditionally recommended for isolated medial collateral ligament injuries, they may also be a hindrance to patients and restrict functional rehabilitation.

The decision whether to use surgical or non-surgical intervention will depend upon the anatomical proximity of the torn ligament ends, and an assessment of their capacity to directly heal or not. Failure of non-surgical management may also indicate conversion to surgical management, should chronic pain or knee joint laxity develop. In the context of associated ligament injuries to the ACL or PCL, the anatomical proximity of the torn medial collateral ligaments is again assessed and the knee joint assessed for medial instability. Injuries to the PMC may not heal with non-surgical management when they occur as part of a multi-ligament injury, and therefore need to be identified to inform appropriate treatment decisions. The anticipated benefits of surgery must be balanced against the risk of complications, such as post-operative infection, and failure of the repair or graft.

The surgical options of direct repair or reconstruction of injured medial knee structures aim to restore normal load-sharing properties of these structures (Wijdicks 2010). In adults, surgical techniques to achieve this may include direct repair of the superficial MCL and POL, advancement of the superficial MCL insertion to the tibia or femur, pes anserinus transfer and a variety of reconstruction strategies. Surgical treatment for combined injuries may involve any combination of reconstruction for all ligaments, ACL reconstruction and MCL repair, ACL reconstruction and non-surgical management of the MCL, or MCL repair and non-surgical management for the ACL (Grant 2012). Early post-operative rehabilitation may require a gradual increase of knee motion and weight-bearing to allow for ligament healing, graft integration and patient comfort.

The surgical options for treating isolated or combined injuries to the medial ligaments of the knee sustained by skeletally immature persons may differ from adults due to the risk of damage to an open physis (bony growth plate) and subsequent growth disturbance. Surgical options may therefore depend upon the skeletal bone age assessed by skeletal plain radiographs and pubertal development using the Tanner scale (Marshall 1969; Marshall 1970), which reflect the extent of remaining growth. Surgical options used in skeletally immature patients can include extraphyseal reconstruction, partial transphyseal reconstruction, or complete transphyseal reconstruction. Post-operative rehabilitation in skeletally immature patients may require extended follow-up to monitor for potential growth disturbance.

Why it is important to do this review

In some populations, injuries to the medial knee ligaments are the most common knee injury (Swenson 2013). More severe injuries, including when in combination with other knee ligament injuries, may lead to chronic joint dysfunction and early degenerative joint changes. The optimal management of MCL injuries remains controversial, in particular, the surgical management of grade III injuries and complex ligamentous injuries that also involve other knee ligaments (Wijdicks 2010). This review will examine and summarise current evidence regarding the management of these injuries in order to help guide their clinical management and future areas of research.

Objectives

To assess the effects (benefits and harms) of interventions for treating injuries to the medial ligaments of the knee. We intend to compare different types of conservative intervention (e.g. no bracing versus bracing), surgical versus conservative intervention, different surgical interventions (e.g. reconstruction versus repair) and early post-operative treatments.

Methods

Criteria for considering studies for this review

Types of studies

We will include randomised and quasi-randomised (method of allocating participants to a treatment which is not strictly random, e.g. by hospital number) controlled clinical trials evaluating interventions for treating injuries of the medial ligaments of the knee.

Types of participants

We will include participants with injuries of the medial ligaments of the knee. We will include isolated injuries involving the medial ligaments of the knee (superficial MCL, deep MCL, POL/PMC) and also combined injuries that involve the medial ligaments of the knee and either the ACL or PCL. We will perform separate analyses of trials specifically focusing on skeletally immature people. We will exclude trials that specifically focus on people with ligamentous injuries of the knee that do not involve isolated or combined injuries of the medial ligaments. We will also exclude trials that focus on people with knee injuries with neurological or vascular impairment of the affected limb.

Types of interventions

We will include all conservative and surgical interventions used in the treatment of medial ligament injuries of the knee. We will exclude trials that evaluate different methods of treating complications of medial knee ligament injuries, such as post-operative instability, chronic pain or infection. We intend to make the following comparisons:

  • Different conservative interventions (e.g. no bracing versus bracing)

  • Surgical versus conservative interventions (e.g. repair versus bracing)

  • Different surgical interventions (direct repair, autograft and allograft reconstructive techniques, and synthetic graft reconstructive techniques)

  • Different early post-operative treatments (e.g. restricted range of motion or weight-bearing versus unrestricted mobilisation). We will exclude comparisons of different exercises to rehabilitate specific muscles and ligaments.

We have set up the following provisional rules for selecting the 'control' intervention for comparisons of different conservative interventions and comparisons of different surgical interventions. For conservative interventions, we will select the treatment that involves the greatest immobilisation (such as in duration of brace use, or restriction of weight-bearing). For surgical interventions, the 'control' intervention will be the most established intervention. For post-operative rehabilitation protocols, this review will include comparison of early post-operative rehabilitation treatments that intervene to control range of motion and weight-bearing functions of the knee.

Types of outcome measures

Primary outcomes
  1. Subjective measures of knee function and patient satisfaction, preferably validated, including the Tegner and Lysholm system (Tegner 1985), the International Knee Documentation Committee scoring systems (symptoms and subjective function sections) (Irrgang 2001) and the Cincinnati knee rating system (Barber-Westin 1999).

  2. Knee pain (post-intervention), at short-, medium- and long-term follow-up.

  3. Treatment failure (re-operation, conversion of conservative to surgical treatment, prolonged physiotherapy for an adverse effect).

Secondary outcomes
  1. Objective knee function (range of motion, isokinetic muscle strength, deformity and instability on clinical examination).

  2. Return to pre-injury activity level (e.g. return to work; return to sports).

  3. Adverse effects: short-term (iatrogenic neurological or vascular injury), medium-term (infection), long-term (persistent instability).

  4. Quality of life measures, preferably validated, including the SF-12, SF-36 and Mohtadi-QoL questionnaire (Mohtadi 1998; Bosse 2009).

  5. Secondary joint degeneration (as assessed by radiographic imaging).

Timing of outcome measurement

Outcome assessment for interventions will be analysed at short-term (up to six months), intermediate-term (six months up to two years) and long-term follow-up (two years or more) after treatment.

Search methods for identification of studies

Electronic searches

We will search the Cochrane Bone, Joint and Muscle Trauma Review Group’s Specialised Register (to present), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, current issue), MEDLINE (1946 to present) and EMBASE (1974 to present). We will also search Current Controlled Trials and the WHO International Clinical Trials Registry Platform for ongoing and recently completed trials. In MEDLINE (Ovid Online), we will combine the subject-specific strategy with the sensitivity-maximising version of the Cochrane Highly Sensitive Search Strategy for identifying randomised trials (Lefebvre 2011). Search strategies for CENTRAL, MEDLINE, and EMBASE can be found in Appendix 1.

We will apply no language restrictions.

Searching other resources

We will also screen the references of all relevant articles and contact authors and experts in the field as necessary to ensure complete data collection.

Data collection and analysis

Selection of studies

Three authors (SBR, NB and GB) will independently screen search results for eligible studies. Where suitable, we will seek full articles for any study judged eligible by any author. The same three authors will perform study selection. We will resolve any disagreements by discussion and majority decision. Any outstanding uncertainties will be resolved by adjudication by the fourth author (TW).

Data extraction and management

Three review authors (SBR, NB, and GB) will independently extract data from each included trial using a pre-designed data extraction form. The extracted data will be collated and sequentially entered into Review Manager software (RevMan 2012). We will record qualitative details and data describing the study groups, interventions and outcomes. We will contact trialists for further details as necessary. We will resolve any differences or disagreements by checking trial reports, contacting trial authors, discussion between the three authors (SBR, NB, and GB) or adjudication by the fourth author (TW).

Assessment of risk of bias in included studies

Three review authors will independently assess the risk of bias in each included study for the following domains: sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, and selective outcome reporting, as well as other sources of bias (e.g. major baseline imbalance, differences in care provider’s experience with the interventions under test, differences in rehabilitation). Each item will be evaluated as being at low, high, or unclear risk of bias (in accordance with the criteria in Table 8.5.c; Higgins 2011a). Any disagreement will be resolved by consensus of these three authors.

Measures of treatment effect

We will calculate risk ratios (RRs) and 95% confidence intervals (CIs) for dichotomous outcomes, and mean differences (MD) and 95% CIs for continuous outcomes. When pooling continuous data for outcomes measured in different ways or scales (e.g. different measures of knee function), we shall use the standardised mean difference (SMD) and 95% CIs.

Unit of analysis issues

We anticipate that the unit of randomisation in trials on this topic will be the individual patient. We will be alert to potential unit of analysis issues. These include those relating to multiple observations of the same outcome (such as for total complications where a patient might have more than one complication) or multiple time points (we will extract data at clinically relevant time points and perform separate analyses for these).

Dealing with missing data

Whenever possible, we will contact study authors to request missing data. We will analyse missing data for dichotomous and continuous data using an available case analysis, and we will perform sensitivity analyses using 'best-worst case' analysis (Gamble 2005) and 'fixed difference' analysis (Higgins 2011b), respectively. We will make explicit the assumptions of any methods used to cope with missing data (Higgins 2011b). We will not impute missing standard deviations unless they can be calculated from standard errors, 95% CIs or exact P values.

Assessment of heterogeneity

We will assess heterogeneity by visual inspection of the forest plot (analysis) along with consideration of the Chi² test (which we will consider to be statistically significant at P < 0.10) and the I² statistic (Higgins 2003). We will interpret the I² results according to Deeks 2011: 0% to 40% might not be important; 30% to 60% may represent moderate heterogeneity; 50% to 90% may represent substantial heterogeneity; and 75% to 100% may represent considerable (very substantial) heterogeneity.

Assessment of reporting biases

If sufficient (at least 10) studies are identified, we will construct funnel plots (trial effect versus standard error) to assess funnel plot asymmetry, which amongst other things could be due to publication bias. We will conduct a test of funnel plot asymmetry for the main outcomes using Egger's test (Egger 1997).

Data synthesis

When considered appropriate, results of comparable groups of trials will be pooled using both fixed-effect and random-effects models. The choice of the model to report will be guided by a careful consideration of the extent of heterogeneity and whether it can be explained, in addition to other factors such as the number and size of studies that are included. We will use 95% CIs throughout. We will consider not pooling data where there is considerable heterogeneity (I² > 75%) that cannot be explained by the diversity of methodological or clinical features among the trials. Where it is not appropriate to pool data, we will still present trial data in the analyses or tables for illustrative purposes and report these in the text.

Subgroup analysis and investigation of heterogeneity

Where data are available, we intend to perform the following subgroup analyses:

  • Grade of ligamentous injury (using the Fetto and Marshall system, or Hughston modification of the American Medical Association Standard Nomenclature of Athletic Injuries (Fetto 1978; American Medical Association 1966; Hughston 1994)).

  • Complexity of injury (isolated injuries to the medial ligament complex (MCL, PMC, or MCL + PMC) versus combined injuries involving the medial ligament complex and cruciate ligaments (MCL + ACL/PCL, PMC + ACL/PCL, or MCL + PMC + ACL/PCL).

  • Patient sports activity (athlete (regular sports participation) versus non-athlete).

  • Timing of injury (acute injury (less than two months since injury) or chronic injury (greater than two months since injury).

We will investigate whether the results of subgroups are significantly different by inspecting the overlap of CIs and performing the test for subgroup differences available in RevMan (RevMan 2012).

Sensitivity analysis

If appropriate, we will perform sensitivity analyses examining various aspects of trial and review methodology, including the inclusion of trials at high or unclear risk of bias (such as from lack of allocation concealment and lack of blinding of outcome assessors), and of trials only reported in abstracts; and exploring the effects of missing data, and the selection of statistical model (fixed-effect versus random-effects) for pooling. We will also test the effects of excluding mixed population trials that include children.

'Summary of findings' tables

Where evidence is available for key comparisons, such as surgery versus conservative intervention, we will prepare 'Summary of findings' tables. We will use the GRADE approach to assess the quality of evidence related to the primary and first four secondary outcomes listed in the Types of outcome measures section (Higgins 2011c).

Acknowledgements

We thank Helen Handoll, Lindsey Elstub and Laura MacDonald for helping to develop the protocol and for valuable feedback about drafts of the protocol. We are particularly grateful to Joanne Elliott for her help with developing the search strategies. We thank Vincent Eggerding for his contribution during the external referee process.

Appendices

Appendix 1. Cochrane Library and MEDLINE trials search strategy

CENTRAL, The Cochrane Library (Wiley Online Library)

#1 MeSH descriptor: [Medial Collateral Ligament, Knee] this term only
#2 ((medial or posterior oblique) near/3 ligament*):ti,ab,kw (Word variations have been searched)
#3 (MCL or DMCL or SMCL or PMC):ti,ab,kw (Word variations have been searched)
#4 #2 or #3
#5 [mh Knee] or [mh ^"Knee Injuries"] or [mh ^"Knee Joint"]
#6 knee:ti,ab,kw (Word variations have been searched)
#7 #5 or #6
#8 #4 and #7
#9 #1 or #8
#10 MeSH descriptor: [Wounds and Injuries] explode all trees
#11 Any MeSH descriptor with qualifier(s): [Injuries - IN]
#12 injur* or tear* or torn or trauma or rupture* or repair*:ti,ab,kw (Word variations have been searched)
#13 #10 or #11 or #12
#14 #9 and #13 [Trials]

MEDLINE (Ovid Online)

1 Medial Collateral Ligament, Knee/
2 ((medial or posterior oblique) adj3 ligament*).tw.
3 (MCL or DMCL or SMCL or PMC).tw.
4 2 or 3
5 Knee/ or Knee Injuries/ or Knee Joint/
6 knee.tw.
7 5 or 6
8 4 and 7
9 1 or 8
10 exp "Wounds and Injuries"/
11 injuries.fs.
12 (injur* or tear* or torn or trauma or rupture* or repair*).tw.
13 10 or 11 or 12
14 9 and 13
15 Randomized controlled trial.pt.
16 Controlled clinical trial.pt.
17 randomized.ab.
18 placebo.ab.
19 Drug Therapy.fs.
20 randomly.ab.
21 trial.ab.
22 groups.ab.
23 or/15-22
24 exp Animals/ not Humans/
25 23 not 24
26 14 and 25

EMBASE (Ovid Online)

1 ((medial or posterior oblique) adj3 ligament*).tw.
2 (MCL or DMCL or SMCL or PMC).tw.
3 1 or 2
4 exp Knee Ligament/ or exp Knee Injury/ or exp Knee Surgery/ or exp Knee/
5 knee.tw.
6 4 or 5
7 exp Injury/
8 (injur* or tear* or torn or trauma* or rupture* or repair*).tw.
9 7 or 8
10 3 and 6 and 9
11 Randomized Controlled Trial/
12 Clinical Trial/
13 Controlled Clinical Trial/
14 Randomization/
15 Single blind procedure/
16 Double blind procedure/
17 Crossover procedure/
18 Placebo/
19 Prospective Study/
20 ((clinical or controlled or comparative or placebo or prospective* or randomi#ed) adj3 (trial or study)).tw.
21 (random* adj7 (allocat* or allot* or assign* or basis* or divid* or order*)).tw.
22 ((singl* or doubl* or trebl* or tripl*) adj7 (blind* or mask*)).tw.
23 (cross?over* or (cross adj1 over*)).tw.
24 ((allocat* or allot* or assign* or divid*) adj3 (condition* or experiment* or intervention* or treatment* or therap* or control* or group*)).tw.
25 RCT.tw.
26 or/11-25
27 Case Study/ or Abstract Report/ or Letter/
28 26 not 27
29 (exp Animal/ or animal.hw. or Nonhuman/) not (exp Human/ or Human Cell/ or (human or humans).ti.)
30 28 not 29
31 10 and 30

Contributions of authors

Simon B Roberts (SBR), Nick Beattie (NB), Gavin Brown (GB) and Tim White (TW) conceived and developed the protocol. SBR, NB and GB are the guarantors.

Declarations of interest

Simon B Roberts: none known
Nick Beattie: none known
Gavin Brown: none known
Tim White: I have a consultancy contract with Acumed LLP relating to the development of the Fibular Nail which is a novel device for the treatment of ankle fractures.

Ancillary