Dr Edward Wilson, a medical officer to Scott's Antarctic expedition (1910-1912), unwittingly gave the first account of what was probably a chronic exertional compartment syndrome (CECS). This was an account of his own and Scott's diary, which was recovered from the expedition in which he perished.1 French and Price were the first to correlate symptoms with a documented increased intracompartmental pressures (ICPs).2 There are various other terminologies used to describe the condition including anterior tibial pain, chronic compartment syndrome, anterior compartment syndrome, recurrent compartment syndrome, idiopathic compartment syndrome, nontraumatic compartment syndrome of the lower extremity, pain in limb, and transient paralysis of limb.3
Chronic exertional compartment syndrome is a condition of pain induced by exercise, swelling, and impaired muscle function4,5 in young active individual and athletes, particularly those involved in running sports and military training. Usually bilateral, it can arise from insufficient compliance of the surrounding fascia or exercise-induced muscle hypertrophy, which can increase the muscle volume by 20% within the confined nonelastic space of the compartment.6
Physiopathologically, an abnormal increase in muscle compartment pressure interferes with tissue circulation and may cause ischemia and, at times, temporary neurological deficits.7,8 During dynamic exercise, the skeletal muscle is not perfused when contracted,9 as arterial inflow reaches its vascular bed only during muscle relaxation, between 2 contractions.10 An increase in the muscle relaxation pressure, the lowest value of intramuscular pressure between 2 muscle contractions, may therefore impede muscle blood flow during exercise, resulting in ischemic pain and impaired muscle function. In addition, compression of neurological structures may lead to neurological deficits.8,11,12 Chronic exertional compartment syndrome may develop in any muscle harboring an enveloping fascia, such as a thigh, an arm, and the foot.13 Chronic exertional compartment syndrome may be present in all 4 compartments (anterior, lateral, superficial posterior, and deep posterior). The anterior and deep posterior compartments are most frequently affected (25% each) and may simultaneously involve in 8% of cases.14 Chronic exertional compartment syndrome is not commonly reported in the superficial posterior compartment and occurs bilaterally in 37% to 82% of symptomatic athletes.14–17 Anabolic steroids and eccentric exercises induce muscular hypertrophy, increase ICP, and decrease fascial elasticity, predisposing to the development of CECS. Other potential causes are myofascial scarring, venous hypertension, and posttraumatic soft tissue inflammation. History and physical examination may raise the suspicion of CECS, but other causes of lower leg pain exacerbated by exercise have to be excluded.17–19
The ischemic pain, secondary to a nonphysiological increase in compartment pressure, generally subsides after exercise and resolves with rest, within several minutes.13 In contrast to the fairly well clinically defined picture in CECS of the anterior compartment of the leg, superficial and deep posterior CECS complaints are less defined, and some conditions, such as medial tibial stress syndrome, popliteal artery entrapment syndrome, myopathy, and sural nerve entrapment syndrome, have to be considered in the differential diagnosis.13 Anterolateral leg pain radiating to the dorsum of the foot commonly occurs in anterior and lateral CECS, whereas pain, neurological symptoms, and a feeling of tightness typically affecting the medial tibial edge are more frequent in deep posterior CECS.18 The definitive diagnosis is reached when dynamic intramuscular compartment pressures of the lower extremity are elevated.20
Commonly, measurements are obtained before, during, and after exercise,9 but postexercise elevated ICP are the best-documented, available, practical, objective parameter to confirm this syndrome. The introduction of a needle or catheter through the skin and fascia into the muscular compartment makes this procedure somewhat invasive, and painful, with risks of bleeding, neuropraxia, and infection. Among noninvasive diagnostic methods, magnetic resonance imaging (MRI)19,21–23 seems to be a promising alternative. Near-infrared spectroscopy (NIRS) aims to measure the hemoglobin saturation of tissues. Patients with typical complaints and elevated ICPs show a larger decrease in StO2 after exercise than those without pressure elevation or healthy controls.8,24,25 Although all 3 methods (ICP measurement, MRI, and NIRS) seem to be useful in confirming CECS, the role of MRI and NIRS in clinical diagnosis is yet to be established, and there is no consensus as to what ICP levels are to be used for diagnosing CECS.
We therefore reviewed systematically the relevant published evidence on diagnostic criteria commonly in use for CECS. We wished to address 3 main questions: (1) Is there a standard diagnostic method available? (2) What ICP criteria should be used for diagnosing CECS? (3) What are the criteria and options for surgical management? Finally, we made statements on the strength of each diagnostic criterion of ICP based on a rigorous standardized process.
MATERIALS AND METHODS
This systematic review was performed in accordance with the review protocol defined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (www.prisma-statement.org/).
Studies that investigated ICP measurements in diagnosing CECS in the leg of human subjects were considered for the study. The articles also had to be a full report of a clinical study published in the peer-reviewed literature after 1980. Review articles, meeting abstracts, case reports, letters, bulletins, comments, and studies not reporting quantified results were excluded from analysis.
Information Sources and Search
A broad search was performed in August 2011 using PubMed, Score, PEDRO, Cochrane, Scopus, SportDiscus, Web of Knowledge, and Google Scholar to identify relevant articles. The correlation of CECS history and symptoms with raised ICP was first carried out by French and Price in the early 1960s.19 Hence, we restricted the search to articles between 1960 and 2011. Initial searches were performed using the phrase “chronic exertional compartment syndrome.” The phrase “compartment syndrome” was then combined using Boolean connectors (“OR” and “AND”) with the words “diagnosis,” “parameters,” “levels,” “localisation,” or “measurement” (see Appendix 1, Supplemental Digital Content 1, http://links.lww.com/JSM/A20, which lists the full PubMed search strategy). Additional citations were identified by searching the bibliographies of the review articles identified by assessing the references contained within each article. The search was also performed using the other phrases used to describe CECS including “anterior tibial pain,” “anterior compartment syndrome,” “chronic compartment syndrome,” and “non-traumatic compartment syndrome.” All articles not available online were obtained from the British Library, Royal Society of Medicine Library, or the British Medical Association Library.
Study Selection and Data Collection
The results of the search were assessed jointly by 2 reviewers (O.A. and A.D.B.) to identify potentially relevant articles. Conflicts between reviewers were resolved by discussion, until there was 100% agreement on the final studies to be included. A table with the required data items was developed for data extraction, pilot tested on 5 randomly selected studies, and adjusted accordingly.
Data extracted from each study included study design, number of subjects, number of controls, ICP instrument used, compartments measured, limb position during measurements, catheter position, exercise protocol, timing of measurements, mean resting compartment pressures, mean maximal compartment pressures, mean postexercise compartment pressures, diagnostic criteria used, and whether a reference diagnostic standard was used. We considered symptomatic improvement after fasciotomy as the valid diagnostic reference standard for CECS.
Assessing the Quality of Evidence
The quality of studies was assessed based on the approach used by the American Academy of Orthopaedic Surgeons (AAOS) in judging the quality of diagnostic studies.26 This is a 2-step process. First, studies enrolling a prospective cohort of patients or using the valid diagnostic reference standard were initially categorized as level I studies. Any studies that did not enroll the appropriate spectrum of patients (eg, case-control studies) or did not involve a reference standard (studies of diagnostic yield only) were initially categorized as a level IV study. Next, the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)27 instrument was used to identify potential bias and assess variability and quality (see Appendix 2, Supplemental Digital Content 2, http://links.lww.com/JSM/A21, which includes a copy of the QUADAS instrument). Each time a quality standard was not met, we downgraded the level of evidence by one level in a cumulative manner.
Recommendations were made regarding each ICP diagnostic criteria in the literature by taking into account the quality and quantity of the available studies proposing each criterion. This is shown in Table 1 and was based on the AAOS's method in defining the strength of recommendations.
Methods of Analyses
We recorded the mean ICP recordings before, during, and after exercise reported by each study. If these data were presented graphically, means were measured from the graphs. The data extracted was then plotted on graphs using Microsoft Excel 2007 (Microsoft Corporation, Redmond, Washington). We plotted median pressures if mean values were not stated by the authors.
Overall, 3906 potentially relevant publications were identified by the search strategy, with a further 10 being identified after reviewing references from relevant studies. Duplicates were removed, giving a total of 1190 articles. Of these, 1112 articles were excluded from analysis after review of the abstract. Of the remaining 78 studies, a further 46 were excluded after reviewing the full text (Figure 1). Therefore, 32 studies were finally included in the review.
Study Characteristics and Results Synthesis
The characteristics of the studies included are presented in Table 2. The studies varied in the ICP measurement techniques used. The most commonly used technique was the slit catheter, used by 10 studies (31%). It involves cannulating a slit catheter, primed with heparinized saline via a Medicut (Covidien, Tullamore, Republic of Ireland) needle, and linking the catheter to a pressure transducer and recording system. Its main advantage is allowing the ICP to be measured during the patient's physical activity that provokes the symptoms.44 The needle manometer, Wick catheter, and microcapillary infusion techniques followed and were equally common. Awbrey et al28 and Fronek et al30 used 2 methods with the slit catheter and needle manometer in the former, and slit catheter and Wick catheter in the latter. Garcia-Mata et al17 and McDermott et al12 used a Micro-tip (Millar Instruments Inc, Houston, Texas) transducer technique, a more recent method using solid-state intracompartment transducers, with the main advantage of no risk of blockage from either blood or muscle, although it is limited in acquiring online dynamic data while exercising.45 Solid-state transducer intracompartmental catheter by McDermott et al has the added advantage of providing highly sensitive dynamic recordings of ICP and is less susceptible to transducer movements during exercise.
The most commonly measured compartment was the anterior muscle compartment, and the exercise protocol varied between running, walking, and ankle plantarflexion and dorsiflexion exercises. Fronek et al,30 Schepsis et al,37 and Pedowitz et al33 conducted a running exercise in those patients who did not have symptoms following the ankle plantarflexion and dorsiflexion protocol. Only 8 studies (25%) noted the position of the catheter within the leg, and this varied between each. This is important to note because catheter position may affect the compartment pressure readings.46 Furthermore, controversy regarding the existence of more than 1 deep posterior compartment adds another confounding variable to measurements taken from this compartment.47
Ankle and knee position pressures can also affect readings,48 yet most studies did not record the precise position of the ankle and knee. Those that did varied between 20-degree ankle plantarflexion,37 30-degree ankle plantarflexion,30 and 45-degree knee flexion.8
Figures 2 to 6 show the mean ICP measurements from the various studies included in the systematic review. Where authors reported results from multiple compartments, we displayed the reports from the “anterior compartment” group. Before exercise, mean values ranged from 7.4 to 50.8 mm Hg for CECS patients and 5.7 to 12 mm Hg in controls (Figure 2). The studies reporting measurements during exercise showed mean pressure readings ranging from 42 to 150 mm Hg in patients and 28 to 141 mm Hg in controls (Figure 3). The highest reported mean of 150 and 141 mm Hg in patients and controls, respectively,9 represents mean contraction pressures (MCPs). In this study, the authors conclude that MCP is an unreliable parameter for diagnosing CECS because it did not correlate well with increased ICP at rest partly due to the fact that the MCP is related to the force output of skeletal muscle.49 When pain develops in CECS legs, the force output and hence MCP can decrease.8 However, 10 studies (31%) reported mean ICP measurements immediately after exercise (Figure 4). These ranged from 34 to 80 mm Hg in patients and 19 to 36 mm Hg in controls (the latter range being median values). In 6 studies, mean ICP pressures at 1 minute after exercise were stated, ranging from 34 to 55.4 mm Hg and 9 to 19 mm Hg in CECS patients and controls, respectively (Figure 5). Finally, at 5 minutes after exercise, 12 studies reported mean ICP pressures that ranged from 19.1 to 41.2 mm Hg and 8 to 24 mm Hg (median value) in CECS patients and controls, respectively (Figure 6). These ranges show that there is an overlap in ICP readings between normal and symptomatic individuals at each ICP measurement interval. This is somewhat expected taking into account the differences mentioned above in exercise and measurement protocol between each study. An added factor postexercise is residual low-level muscle activity, which normal subjects may have.43 Nevertheless, the mean ICP at 1 minute after exercise did not appear to overlap between subjects and controls in the included studies, suggesting that this may be a reliable timing interval, although only 6 studies (19%) reported measurements at this point.
Risk of Bias and Quality of Evidence
The quality of the articles was generally not high (Table 3). Using the quality assessment of diagnostic accuracy studies methodology checklist,27 most studies did not clearly specify inclusion or exclusion criteria, and 12 studies (38%) did not use a valid reference standard. This includes the study by Pedowitz et al,33 which reports the most widely used criteria. Moreover, in all the studies that did include a valid reference standard, the control groups did not receive confirmation of the diagnoses with this standard (partial verification bias). This may have been difficult because most of the control subjects were asymptomatic and fasciotomy could not be ethically justified in these controls. In these studies, there was also no mention as to whether the reference standard results were interpreted without the knowledge of the results of the index test (diagnostic review bias or blinding).
Nine studies (28%) did not enroll a prospective cohort of patients. Some recruited a spectrum of patients not representative of all the patients who will be receiving the test in practice22,25 (spectrum bias). In these studies, the volunteers were military personnel.
The size of the samples used was generally small, with most studies recruiting either no or a small selection of controls, with the exception of the retrospective study by Turnipseed,18 which included 226 subjects and 50 controls (Table 2). In that study, 136 of 138 patients (98.5%) confirmed to have CECS had complete resolution of symptoms after fasciotomy.
Based on the process outlined in Table 1 to define the strength of recommendations, we found the evidence for commonly used ICP criteria in diagnosing CECS to be weak (Table 4).
The diagnosis of CECS is often unclear,42 especially in the early phases of the onset of symptoms, when ICP values are normal or borderline, and symptoms are poorly defined. Over time, in more advanced stages, symptoms are increasingly better defined, depending on athlete's endurance, and ICP values may definitively confirm this pathology.18,41 Differential diagnosis is mandatory, especially from tibial periostitis, stress fractures, stress reaction, superficial peroneal nerve entrapment,50 effort-induced rhabdomyolysis, myopathy with intolerance of exercise,51 and external iliac artery endofibrosis.52 Dynamic popliteal artery entrapment syndrome, although rare, may lead to misdiagnosis37 of posterior CECS. Rarely, effort-induced venous thrombosis or popliteal artery aneurysm can be confounded for CECS. The diagnosis of CECS is usually confirmed by ICP measurements. At present, no consensus has been reached on the optimal regimen and optimal moment to measure pressures, a large range of compartmental pressure values are considered pathological for CECS,13 and normal ranges are still debated.37
The largest study to date, with 226 subjects, sets the normal compartment pressure threshold at rest as lower 15 mm Hg with borderline pressures being 16 to 24 mm Hg and abnormal values consistent with diagnosis of CECS as above 25 mm Hg.18 Although resting compartment pressures are usually increased in patients with CECS, borderline pressures (16-24 mm Hg) may be recorded, particularly in subjects inactive for a long period before the clinical assessment.18 The study however has several methodological flaws when assessed against the QUADAS27 instrument. These include retrospective recruitment, no clear selection criteria, and an inadequate index test execution description (no mention of limb or catheter position during testing).
Compartment pressures increase 3 or 4 times from baseline and return to normality within a few minutes in normal subjects, whereas they increase markedly and take longer time to return to their baseline values (>10 minutes) in patients with latent CECS.36,53 Dynamic pressure measurements are controversial16,36,38 and are rarely used. Even though relaxation ICP values are considered normal if ranging from 15 to 25 mm Hg, and pathological for CECS when ranged from 34 to 55 mm Hg,4,9,38 ICP values recorded during exercise are often unnecessary and difficult to control and interpret,33 with no feasible valid standardization criteria. Moreover, the response of the manometer is often not as fast as the footspeed. On the other hand, postexertion ICP is more convenient to measure, with no discomforts from placement of an intramuscular catheter during exercise. However, these measurements depend on catheter depth, physical activity before assessment (climbing stairs, prolonged ambulation), and postexercise residual low-level muscle activity.43 Currently, the most widely accepted diagnostic criteria have been established as a basal pressure of >15 mm Hg, >30 mm Hg 1 minute after stopping exercise, and >20 mm Hg at 5 minutes.33 Nevertheless, assessing the diagnostic studies, which support these commonly used accepted criteria, we have found the strength of evidence supporting them to be surprisingly weak (Table 4).
The anterior tibial compartment is the most common location to assess, easy to be accessed, but no standard protocols have been published on ICP measurements, and further data on asymptomatic subjects are needed.22 On the other hand, several aspects of superficial and deep posterior CECS remain unclear, and relatively few long-term data have been published. Most of these studies involve relatively small cohorts of patients, given its low incidence, and it may therefore be difficult to complete a randomized trial on various regimens in superficial and deep posterior CECS.13
Diagnostic noninvasive tools are increasingly emerging. Magnetic resonance imaging is noninvasive and reliable to perform after exercise21,54 and may show findings similar to those observed in metabolic rhabdomyolysis, muscle lesions, or exercise-induced changes.54 Thallium stress testing is promising,55 but published evidence is lacking. Near-infrared spectroscopy is an indirect tool to monitor tissue oxygenation of exercising skeletal muscle and to detect the status of deoxygenation caused by high ICP. Balduini et al29 used nuclear magnetic resonance spectroscopy to detect changes in the concentration of phosphocreatine and found no differences between 12 patients who met the criteria for CECS and 14 patients who did not. In the patients with CECS, deoxygenation during exercise reached a level similar to that induced by tourniquet ischemia.8 This extreme deoxygenation suggests that ischemia is important in the pathophysiology of CECS.8
van den Brand et al25 found 90% sensitivity and 63% specificity for NIRS, with statistically significant differences in StO2 measurements between healthy volunteers and patients with CECS and between prefasciotomy and postfasciotomy values.25 Postfasciotomy, ICP, and StO2 measurements are similar to those observed in healthy volunteers, whereas CECS increases deoxygenation in the anterior compartment during exercise. These findings confirmed those of previous studies.8,24
Although NIRS seems to be informative in patients with anterior CECS,13,25 light absorption could be altered.8 Therefore, the anterior tibialis muscle, being superficial, is much more easily monitored than the deep posterior compartment. At present, it is not possible to develop diagnostic criteria on the basis of the magnitude of deoxygenation because the continuous dual wavelength near-infrared spectrometer does not provide absolute values of oxygenation.8 A prospective study demonstrated the lack of correlation between increased ICP in subjects with exercise-related pain in the lower leg and muscle hypoperfusion evaluated with tetrofosmin spectrometer.32 Of 6 subjects with CECS, only 3 showed scintigraphic hypoperfusion (sensitivity 50%), and 3 of 8 subjects without CECS demonstrated hypoperfusion (specificity 63%) when considering pressure measurements as the standard.32 With these tracer techniques, the measurement of muscle perfusion in different muscle compartments are not absolute flow values, but the flow is normalized to other muscle compartments and compared with normalized resting values. Increased CP could be related to abnormal water transport from the capillaries, inducing decreased arteriovenous pressure gradient, and reduced capillary perfusion. In this context, decrease in pH, hypoxia, and tissue edema further increase ICP. Many of these changes have been investigated using MRI, which when performed at rest and immediately after muscular exercise is a diagnostic option for CECS.21,23 At present, the diagnostic value of MRI is somewhat disappointing when compared with that of ICP and NIRS.19 In patients with CECS, the increase in the AvT2 was larger in the anterior than in the superficial posterior compartment.19 After exercise, the percentage AvT2 increase in the anterior compartment was larger for patients with CECS, with a clear increase in the anterior to posterior ratio when the postexercise values were compared with those preexercise. However, the magnitude of this change in ratio could be reduced when more pronounced and advanced symptoms of CECS are reported. Magnetic resonance imaging was clearly less suitable to confirm this diagnosis.19
In terms of management, a conservative approach is indicated in patients with pressure values below cutoff points.13 Symptoms may persist and sometimes worsen over time,15 and conservative management usually fails; surgical compartment release offers the highest chance of resolution of symptoms being effective in 81% to 100% patients6,31,36,41 unresponsive to conservative measures and complaining of progression of symptoms and paresthesia.18 Fasciotomy reduces ICP9,42 and is curative if the diagnosis is correct.42 Some authors advocate a single incision fasciotomy performed in the middle third of the leg,37,56 and some prefer a double incision because it allows better visualization of the fascial passage of the superficial peroneal nerve.37 Fasciotomy of the anterior compartment has a success rate of 80% to 100%,5,16,37,42 if patients are correctly selected36; partial fasciotomy is complicated by a high recurrence rate.57 After surgery, most patients with CECS improve in terms of pain relief and are satisfied, but the pain relief is not in relationship with the great improvement in postexercise compartment measurements. In most previously published experiences, fasciotomy is performed in patients with recurrences after fasciotomy.18
Limitations of Our Study
We considered symptomatic improvement after fasciotomy as the valid diagnostic reference standard. This however can depend on the surgical factors mentioned above and therefore may not be suitable as the chosen gold standard.
Elevated ICP are currently accepted as the gold standard diagnostic criterion for CECS, but studies outlining these criteria have no high-level evidence as assessed using the AAOS protocol. Studies in which an independent blinded comparison is made with a valid reference standard among consecutive patients are yet to be undertaken. It is also evident that there should be an agreed ICP test protocol for diagnosing CECS because the variability here contributes to the large differences in ICP measurements and hence diagnostic thresholds between studies. Current ICP pressure criteria for CECS diagnosis are therefore unreliable and emphasis should remain on good history. Clinicians may however consider measurements taken at 1 minute after exercise because mean levels at this timing interval only did not overlap between subjects and controls in the studies we analyzed. Levels above the highest reported value for controls here (27.5 mm Hg) along with a good history should be regarded as highly suggestive of CECS. One of the authors' (N.P.) current practice is to use the slit catheter method with a recording device displaying “on-line” measurements to check for catheter patency, placement, blockage, and displacement.
It is clear that to achieve an objective recommendation for ICP threshold, there is a need to set up a multicenter study group to reach an agreed testing protocol. Group members can also modify the preliminary recommendations we have made by evaluating the applicability of the evidence in accordance with the guidelines set out by the “Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) group.”58
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