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MRC Dyspnoea Scale - MRC

The MRC Dyspnoea Scale, also called the MRC Breathlessness Scale, has been in use for many years for grading the effect of breathlessness on daily activities. This scale measures perceived respiratory disability, using the World Health Organization (WHO) definition of disability being “any restriction or lack of ability to perform an activity in the manner or within the range considered normal for a human being”.

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Questionnaire on Respiratory Symptoms

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Questionnaire on respiratory symptoms and instructions to interviewers (1966)

Questionnaire on respiratory symptoms and instructions to interviewers (1976)

Questionnaire on respiratory symptoms and instructions to interviewers (1986)

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Modified Medical Research Council Dyspnea Scale in GOLD Classification Better Reflects Physical Activities of Daily Living

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BACKGROUND: In multidimensional Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification, the choice of the symptom assessment instrument (modified Medical Research Council dyspnea scale [mMRC] or COPD assessment test [CAT]) can lead to a different distribution of patients in each quadrant. Considering that physical activities of daily living (PADL) is an important functional outcome in COPD, the objective of this study was to determine which symptom assessment instrument is more strongly associated with and differentiates better the PADL of patients with COPD.

METHODS: The study included 115 subjects with COPD (GOLD 2–4), who were submitted to spirometry, the mMRC, the CAT, and monitoring of PADL (triaxial accelerometer). Subjects were divided into 2 groups using the cutoffs proposed by the multidimensional GOLD classification: mMRC < 2 and ≥ 2 and CAT < 10 and ≥ 10.

RESULTS: Both mMRC and CAT reflected the PADL of COPD subjects. Subjects with mMRC < 2 and CAT < 10 spent less time in physical activities < 1.5 metabolic equivalents of task (METs) (mean of the difference [95% CI] = −62.9 [−94.4 to −31.4], P < .001 vs −71.0 [−116 to −25.9], P = .002) and had a higher number of steps (3,076 [1,999–4,153], P < .001 vs 2,688 [1,042–4,333], P = .002) than subjects with mMRC > 2 and CAT > 10, respectively. Physical activities ≥ 3 METs differed only between mMRC < 2 and mMRC ≥ 2 (39.2 [18.8–59.6], P < .001). Furthermore, only the mMRC was able to predict the PADL alone (time active, r 2 = 0.16; time sedentary, r 2 = 0.12; time ≥ 3 METs, r 2 = 0.12) and associated with lung function (number of steps, r 2 = 0.35; walking time, r 2 = 0.37; time < 1.5 METs, r 2 = 0.25).

CONCLUSIONS: The mMRC should be adopted as the classification criterion for symptom assessment in the GOLD ABCD system when focusing on PADL.

• activities of daily living
• sedentary lifestyle
• symptom assessment
• chronic obstructive pulmonary disease
• GOLD classification
• Introduction

COPD is characterized by chronic and progressive air flow obstruction and several significant systemic manifestations that may result in reduced functional capacity and health status. 1 , 2 Because of the diverse manifestations of this disease, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) proposed in 2011 a multidimensional assessment (GOLD ABCD) of patients based on the severity of air flow obstruction, in addition to the unidimensional classification (GOLD I/II/III/IV). 3 The risk of future exacerbation, assessed by pulmonary function or history of exacerbations, and the symptoms, assessed by the COPD assessment test (CAT) questionnaire or the modified Medical Research Council dyspnea scale (mMRC), were used for classification. This classification system has been recently refined, and the recommendation is that the multidimensional assessment must take into account only the history of exacerbations and the evaluation of symptoms. 4

The relationship between the multidimensional GOLD classification and physical activities in daily life (PADL) has been investigated in some studies. However, results are still controversial, probably because of the large number of framing possibilities in the former classification model. After the new recommendation, part of this difficulty seems to have been remedied because, from now on, the choice for the symptom assessment instrument (CAT or mMRC) represents the only aspect that may cause differences in the multidimensional classification.

Although GOLD states that it is not necessary to use more than one symptom assessment instrument to classify patients, the mMRC and CAT have been observed to have a moderate agreement. 5 , 6 Zogg et al 5 used the 2 symptom assessment instruments and found that the quadrants defined with the use of the mMRC correlated more strongly with the number of steps than did the quadrants established by CAT. Demeyer et al 6 also suggested that the mMRC should be used along with risk assessment to better differentiate the PADL of patients with COPD. On the other hand, Moreira et al 7 used the mMRC to establish the multidimensional GOLD classification and found that this classification was weakly associated with the PADL of patients with COPD.

PADL level is an important functional outcome in COPD because of its relation with the risk of exacerbations, hospitalizations, and mortality. 8 However, because the symptom assessment instrument (mMRC or CAT) chosen can present different distribution of patients in the quadrants of the multidimensional classification, it is not clear whether the mMRC or CAT reflects their functional status in distinct ways. Therefore, the aim of the present study was to determine which symptom assessment instrument differentiates better the PADL of subjects with COPD and which is most strongly associated with this outcome.

Current knowledge

In the multidimensional Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification, 2 instruments can be used for symptom evaluation. The choice of instrument (modified Medical Research Council dyspnea scale [mMRC] or COPD assessment test [CAT]) can lead to a different categorization of patients in each quadrant.

What this paper contributes to our knowledge

The symptom assessment instrument used in the multidimensional GOLD classification can cause differences in the distribution of patients between the ABCD quadrants and also in the potential to reflect their physical activity of daily living. The mMRC must be used instead of the CAT when the goal is to better discriminate the physical activity of daily living, including the sedentary behavior.

Participants

Participants of the study were subjects with COPD referred to the Center of Assistance, Teaching, and Research in Pulmonary Rehabilitation (NuReab), and the recruitment occurred from March 2013 to August 2016. The inclusion criteria were: clinical diagnosis of COPD with spirometric classification II–IV 9 , age ≥ 40 y, and clinical stability in the last month preceding the beginning of the protocol. The study excluded active smokers, patients with COPD exacerbation during the study protocol, and patients with other respiratory, cardiovascular, neurological, musculoskeletal, and rheumatologic diseases that could influence the execution of the assessments proposed.

This study was approved by the Ethics Committee on Human Research of the University of the State of Santa Catarina - Florianópolis/SC, Brazil (CAAE: 38765814.7.0000.0118). All participants signed an informed consent form.

Sample Size

The sample size was calculated based on data from a pilot study with 20 subjects (14 men; 65 ± 6 y; 54.4 ± 35.6 pack-years; percent-of-predicted FEV 1 = 37.5 ± 15.1%; body mass index = 26.2 ± 4.49 kg/m 2 ), using the software G*Power 3.1.9.2. We use the mean of the difference and the highest SD of the number of steps and the walking time among subjects classified with mMRC < 2 and ≥ 2 (4,493 ± 3,328 steps and 53.8 ± 36.8 min) and CAT < 10 and ≥ 10 (1,996 ± 3,416 steps and 18.8 ± 40.8 min). Considering the estimation power of 80% and α of .05, a maximum sample size of 104 subjects was found. In addition, to obtain a reliable measure of the number of steps (0.80 < intraclass correlation coefficient > 0.85) on 2 days of monitoring of the ADL, a sample size of approximately 100 subjects is required. 10

This was a cross-sectional study with protocol carried out in 3 d. Subjects were submitted to lung function assessment, the mMRC, and the CAT questionnaire and to the monitoring of PADL.

Pulmonary Function

Pulmonary function was assessed with a portable EasyOne spirometer (ndd Medical Technologies, Zurich, Switzerland), whose calibration was checked before each assessment, following the methods and criteria recommended by the American Thoracic Society/European Respiratory Society. 11 Spirometric measurements were obtained before inhalation of 400 μg of bronchodilator and 15 min after this. Equations proposed for the Brazilian population were used for calculation of predicted values. 12

Subjects were divided into 2 groups for analysis using the cutoffs proposed by the multidimensional GOLD classification 1 : subjects with mMRC < 2 and mMRC ≥ 2 and those with CAT < 10 and CAT ≥ 10.

To evaluate the PADL, we used a triaxial accelerometer (DynaPort activity monitor, McRoberts BV, Hague, Netherlands). 13 Monitoring took place on 2 consecutive weekdays, lasting 12 h from awakening. The mean of both days was considered for data analysis. In a previous study, 2 days of assessment were considered necessary to achieve a reliable measure (0.70 < intraclass reliability coefficient < 0.88). 14 All participants received an explanatory manual and were instructed on how to use the equipment and register the exact time of placement and removal. Data processing and analysis were performed with the MiRA2 software (McRoberts BV, Hague, Netherlands). In cases of error of measurement after data processing and analysis, the subject used the equipment again. The following variables were considered: time spent standing, sitting, lying, and walking; movement intensity during walking; energy expenditure in PADL; and number of steps.

The sum of the time spent standing and walking corresponded to the active time, and the sum of the time spent sitting and lying represented the sedentary time. The time spent with sedentary behavior was also evaluated, considering physical activities with energy expenditure < 1.5 metabolic equivalents of task (METs). 15 In this case, a time of ≥ 8.5 h corresponds to inactivity. 16

The time spent in moderate and vigorous physical activity (≥ 3 METs), with a cutoff point of 80 min/d, was used to categorize subjects as to their level of physical (in)activity. Subjects were considered either active (physical activities ≥ 80 min/d) or inactive (physical activities < 80 min/d). 17 The number of steps was used to categorize severe physical inactivity (< 4,580 steps). 18

Statistical Analysis

Data were processed in the SPSS 20.0 (SPSS, Chicago, Illinois) and GraphPad Prism 5 (GraphPad Software, La Jolla, California) software. Data distribution was tested using the Kolmogorov-Smirnov test. The Chi-square test was used to check associations between the level of PADL and the mMRC groups < 2 or ≥ 2 and CAT < 10 or ≥ 10. The Cramer V coefficient demonstrated the strength of these associations. Simple and multiple linear regressions using the stepwise method were applied. The CAT, mMRC, and FEV 1 (percent of predicted) were considered as dependent variables, and the PADL was considered an independent variable. Correlations between CAT, mMRC, and PADL were tested using the Pearson or Spearman correlation coefficient. The intraclass correlation coefficient between days 1 and 2 of the ADL monitoring was calculated. The level of significance adopted was P < .05.

One hundred twenty-five subjects were recruited for the study, and 115 were potentially eligible. Five of these were excluded; 3 for not meeting the spirometric criteria for diagnosis of COPD and 2 for exacerbation of the disease during the protocol. Thus, 110 subjects (75 men; 68.2%) completed the study. Anthropometric data, pulmonary function, PADL, dyspnea, and health status are shown in Table 1 . The intraclass correlation coefficient for the PADL variables was > 0.80.

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Anthropometric Characteristics, Lung Function, Functional Status, Dyspnea, and Health Status

ADL Between the mMRC Cutoff 2 and CAT Cutoff 10

Fifty-one subjects presented mMRC < 2 (GOLD A and C), whereas 57 subjects had mMRC ≥ 2 (GOLD B and D). Subjects with mMRC < 2 spent less time sitting, sedentary, and in physical activities < 1.5 METs (mean of the difference [95% CI] = −50.7 min [−90.4 to −11.4 min] P = .01, −62.2 min [−99.8 to −24.5 min] P = .002, and −62.9 min [−94.4 to −31.4 min] P < .001, respectively) and had a higher number of steps and time standing, walking, active, and in physical activities ≥ 3 METs (mean of the difference [95% CI] = 3,076 [1,999–4,153] P < .001, 25.7 min [2.12–49.3 min] P = .033, 35.0 min [22.3–47.8 min] P < .001, 70.8 min [35.5–106 min] P < .001, and 39.2 min [18.8–59.6 min] P < .001, respectively). There were no significant differences between groups (mean of the difference [95% CI] = −11.5 min [−44.5 to 21.5 min], P = .300) with respect to the lying time.

Sixteen subjects presented CAT <10 (GOLD A and C), whereas 94 subjects presented CAT ≥ 10 (GOLD B and D). Subjects with CAT < 10 spent less time in physical activities < 1.5 METs (mean of the difference [95% CI] = −71.0 min [−116 to −25.9 min], P = .002) and had a higher number of steps and time walking and active (mean of the difference [95% CI] = 2,688 [1,042–4,333] P = .002, 33.0 min [13.8–52.2 min] P = .002, and 59.3 min [7.45–111 min] P = .036, respectively). Time sitting, lying, standing, and in physical activities ≥ 3 METs were similar between the 2 groups (mean of the difference [95% CI] = −50.3 min [−107 to 5.92 min] P = .08, −4.39 [−51.3 to 42.6 min] P = .83, 17.9 min [−15.5 to 51.4 min] P = .34, and 15.9 min [−14.3 to 46.0 min] P = .08, respectively). Figure 1 shows the main results of comparisons between mMRC < 2 and ≥ 2 (A) and between CAT < 10 and ≥ 10 (B).

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Comparisons of time walking, active time, sedentary time, time in physical activity < 1.5 metabolic equivalents of task (METs), and time in physical activity ≥ 3 METs between Modified Medical Research Council dyspnea scale (mMRC) (A) and COPD assessment test (CAT) (B). Center lines represent the median; the top and bottom lines (box) represent interquartile range; and top and bottom whiskers represent quartile 3 + 1.5 (quartile 3 − quartile 1) and quartile 1 − 1.5 (quartile 3 − quartile 1), respectively.

Both classifications, the ones based on cutoff of 2 for mMRC and 10 for CAT, were associated with the classification based on the cutoff of 80 min in physical activities ≥ 3 METs, with the sedentarism classification based on the cutoff point of 8.5 h in physical activities < 1.5 METs and with the severe physical inactivity based on the cutoff of 4,580 steps/d. Details of results of the associations are listed in Table 2 .

Distribution of Subjects' Physical Activity in Daily Life Outcomes and Association With the Modified Medical Research Council Dyspnea Scale Cutoff 2 and COPD Assessment Test Cutoff 10

Correlations Between Physical Activity in Daily Life and Dyspnea, Health Status, and Pulmonary Function

The mMRC generally showed stronger correlation with PADL than CAT. The results of the correlations between PADL variables and mMRC, CAT, and FEV 1 (in liters and percent predicted) are described in Table 3 .

Correlation Coefficient Between Physical Activity in Daily Life Variables and Dyspnea, Health Status, and Pulmonary Function

Simple Linear Regression and Predictive Models for ADL

The variability of FEV 1 percent predicted, mMRC, and CAT were able to explain, in isolation, 23 ( P < .001), 29 ( P < .001), and 17% ( P < .001) of the variability in the number of steps, respectively; 26 ( P < .001), 28 ( P < .001), and 17% ( P < .001) of the variability of the time walking; 8 ( P = .002), 16 ( P < .001), and 8% ( P = .003) of the variability of active time; 7 ( P = .006), 12 ( P < .001), and 7% ( P = .007) of the variability of sedentary time; and 21 ( P < .001), 17 ( P < .001), and 11% ( P < .001) of the variability of time in physical activities < 1.5 METs, respectively. The variability of the time in physical activities ≥ 3 METs was explained in 12% by mMRC ( P < .001) and in 5% by CAT ( P = .02), whereas percent-of-predicted FEV 1 was not able to explain this variable ( P = .055).

When tested in predictive models for variables of PADL, it was observed that CAT was not retained in any of them, whereas mMRC was in all models. The results of multiple regression are presented in Table 4 .

Model Predictor for Time Walking, Time Active, Time Sedentary, Time in Physical Activities ≥ 3 Metabolic Equivalents of Task, and Time in Physical Activities < 1.5 Metabolic Equivalents of Task

The present study aimed to determine which symptom assessment instrument better differentiates the PADL of subjects with COPD and is most strongly associated with this outcome. The main findings demonstrate that although the CAT and mMRC are able to reflect the level of ADL of COPD subjects, the mMRC has a stronger association. Furthermore, only the mMRC was able to predict the PADL alone, and this measure was also associated with lung function.

Since the publication of the new COPD classification model (GOLD ABCD) by GOLD in 2011, noted as an important advance because it incorporated multimodality assessment and symptom burden and highlighted the importance of exacerbation prevention in the management of COPD, 1 a considerable number of studies have sought to analyze the equivalence of different classification criteria 5 , 19 – 27 and their association with important outcomes, such as functional status, 5 – 7 , 28 – 30 quality of life, 29 , 31 , 32 and mortality. 33 – 37 Recently, a systematic review 4 found that there is an average classification disagreement of 13% in all quadrants, depending on the instrument used. The agreement between CAT and mMRC ranged from slight to moderate, and the meta-analysis showed a pooled kappa coefficient of 0.548 (95% CI 0.35–0.70, P < .001; I 2 = 99.3; z = 4.84). These findings indicate that CAT ≥ 10 and mMRC ≥ 2 are not equivalent when assessing symptoms in patients with COPD. 4

In the present study, both symptom assessment instruments were associated with categorizations of PADL (physical activity, sedentarism, and severe inactivity). However, the associations of PADL and symptoms with mMRC score were stronger than with CAT. Also, whereas all variables related to PADL (except for time lying) differed among subjects with mMRC < 2 and mMRC ≥ 2, the time lying, sitting, standing, and in physical activities ≥ 3 METs did not differ between subjects with CAT < 10 and CAT ≥ 10. These findings, added to the fact that CAT was not retained in any predictive model of PADL, suggest that the mMRC better reflects the performance of subjects in their activities than CAT, especially in high-energy expenditure activities (≥ 3 METs). A possible explanation is that although CAT encompasses the major symptoms of patients with COPD, 38 some of its items may not substantially interfere with the realization of PADL, such as cough and expectoration. In contrast, the mMRC specifically rates dyspnea from minimum to maximum physical exertion, symptoms more strongly linked to functional limitations in patients with COPD. 39

In a previous study, 40 the FEV 1 did not show a correlation with certain ADL variables, differing from the findings of the present study, which showed moderate correlations with steps and time walking. Furthermore, in isolation, mMRC and FEV 1 were able to predict a large part of PADL variables and, when combined, explained more strongly the number of steps, the time walking, and the time in physical activities < 1.5 METs. Therefore, although FEV 1 alone does not reflect ADL in patients with COPD as well, it may be possible to achieve a more complete analysis of this outcome when FEV 1 is associated with a symptom scale, as was the case in the previous GOLD ABCD classification based on the mMRC.

To our knowledge, only 3 studies investigating the functional status in the multidimensional GOLD classification have objectively ascertained the differences in PADL between the ABCD quadrants. 5 – 7 In a study developed by Zogg et al 5 among the PADL variables (number of steps, active energy expenditure, level of physical activities, and time in physical activities > 3 METs), only the number of steps differed between quadrants, regardless of the use of CAT or mMRC. However, mMRC correlated more strongly with the number of steps than CAT (r = −0.51 vs r = −0.37, P < .001 in both cases, respectively). Moreira et al 7 showed that both GOLD classifications (A–D and I–IV) are weakly associated with PADL variables (Cramer's V < 0.20 for all). In addition, no differences were found between active and inactive time (physical activities > 2 and 3 METs and physical activities < 2 and 3 METs) between quadrants ( P = .09 to .39). More recently, Demeyer et al 6 showed that the mMRC is preferable when used in combination with risk assessment to differentiate PADL of patients with COPD. Furthermore, regardless of risk assessment, the mMRC can be a good predictor of mortality, 34 , 39 since the higher the score in mMRC, the fewer the number of steps. 6

In contrast to previous studies, this study conducted a more detailed analysis of PADL, including sedentary behavior. Patients with COPD adopt sedentary behavior throughout most of the day, most frequently carrying out physical activities < 1.5 METs in seated or reclined positions. 15 , 41 This pattern of behavior has also been observed even when patients are considered physically active (ie, when they perform ≥ 80 min of moderate to vigorous physical activities per day [≥ 3 METs]). 17 It is known that sedentary behavior is associated with negative health effects in the general population, increasing the risk of cardiovascular and metabolic diseases and mortality. 42 In patients with COPD, the risk of death is about 4 times higher in those who spend > 8.5 h in physical activities < 1.5 METs. 16 Furthermore, for each hour of the day spent in sedentary physical activities, the risk of death increases by 42%. 16 In the present study, only the score on the mMRC correlated with the time in physical activities < 1.5 METs, and the magnitude of the difference observed among subjects with mMRC < 2 and mMRC ≥ 2 was higher than among subjects with CAT < 10 and CAT ≥ 10. These results suggest that the mMRC reflects sedentary behavior better than CAT does.

Thus, the symptom assessment instrument used in the multidimensional GOLD classification can cause not only differences in the distribution of patients between the ABCD quadrants, but also in the potential to reflect their PADL. Therefore, standardizing the choice of the symptom assessment instrument can be a determining factor. This has been discussed in the literature in an analysis of 4 cohort studies. 43 Although GOLD recommends the use of either one of the 2 instruments for the multidimensional classification, 1 the results of the present study suggest that, supported by a previous study, 6 the mMRC must be used instead of the CAT when the goal is to better discriminate the PADL, including the sedentary behavior. It is important to consider this outcome while evaluating patients with COPD, since sedentary behavior has a causal relationship with mortality in the general population 44 and also in these patients. 16

The heterogeneous distribution of subjects in the groups formed by CAT (16 subjects with CAT < 10; 94 subjects with CAT ≥ 10) could be considered a limitation of this study. This may have caused a type-2 error in some comparisons. However, the sample size in the present study exceeded the previous calculation. Furthermore, these same conditions are observed in most studies that have addressed GOLD classifications. 5 – 7 , 24 , 28 , 29 , 31 , 34 The absence of GOLD I subjects in the sample of the present study prevents us from generalizing the results for these patients. However, the selection of patients in the disease's early stages is difficult because underdiagnosis is common, especially at this stage. 1 In addition, GOLD I patients may be asymptomatic, and therefore the impact of the disease may be very low and clinically not significant. PADL analysis performed only in 2 consecutive days could also be considered a limitation of the present study, but both of the variables used to estimate sample size (number of steps and walking time) and sedentary behavior showed high intraclass correlation coefficient values (> 0.80).

To our knowledge, this was the first study to demonstrate that the symptom assessment instrument chosen for the multidimensional GOLD classification results in better differentiation of variables, reflecting physical inactivity and sedentary behavior. Furthermore, only the mMRC score, regardless of association with FEV 1 , was able to explain the variability of PADL in patients with COPD.

• Conclusions

The multidimensional GOLD classification requires standardization regarding the criterion for symptom assessment. Although physical inactivity and sedentary lifestyles are striking features among patients in the D quadrant (mMRC ≥ 2 or CAT ≥ 10), we suggest that the mMRC should be adopted as the classification criterion in the GOLD ABCD system, especially when the focus is the level of PADL.

• Correspondence: Anamaria Fleig Mayer PhD, Physiotherapy Department; Núcleo de Assistência, Ensino e Pesquisa em Reabilitação Pulmonar, Universidade do Estado de Santa Catarina (UDESC), Rua Pascoal Simone, 358, 88080-350, Florianópolis, Brazil. E-mail: anamaria.mayer{at}udesc.br .

The authors have disclosed no conflicts of interest.

• Copyright © 2018 by Daedalus Enterprises
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Kevin C. Chung

3 Professor of Surgery, Section of Plastic Surgery, Assistant Dean for Faculty Affairs, The University of Michigan Medical School

Evaluation of outcomes after peripheral nerve surgeries include a number of assessment methods that reflect different aspects of recovery, including reinnervation, tactile gnosis, integrated sensory and motor function, pain and discomfort, neurophysiological and patient- reported outcomes. This review makes a list of measurements addressing these aspects as well as advantage and disadvantage of each tool. Because of complexities of neurophysiology, assessment remains a difficult process, which requires researchers focus on measurements best relevant to specific conditions and research questions.

The outcomes movement, initiated in 1988 was stimulated by the national emphasis on cost containment and efforts to limit geographic differences in the use of various medical procedures. 1 - 3 Goals of the outcomes movement included “increased understanding of the effectiveness of different interventions, the use of this information to make possible better decision making by physicians and patients, and the development of standards to guide physicians and aid third-party payers in optimizing the use of resources, by investigating and comparing patient experiences.” 1 , 4 Patient experiences can range from mortality, physiologic measures, reduction of symptoms, improvement in daily functioning, clinical events, to patient satisfaction. 4 , 5 The outcomes chosen to evaluate care need to be carefully considered based on criteria that are most pertinent to the patient’s need. Additionally vital are the criteria for selecting outcome measurement instruments, which comprise of reliability, validity, and responsiveness of measures, their clinical utility, and relationship to the care under investigation. 5

Peripheral nerve injuries can be caused by trauma, accidental injuries during extensive surgery, nerve tumors, compressive disease or congenital anomalies, with the majority (81%) located on upper extremity. 6 , 7 Among upper or lower-limb trauma, incidence of nerve injuries is reported to be 1.64%, with crush injuries having the highest rate at 1.9%. 8 These injuries may lead to irreversible disabilities in patients, such as sensory loss, deficient motor function, pain problems in terms of cold intolerance and hyperesthesia, that ultimately impair hand function, and affect quality of life at work and in society. 7 Despite marked advances in the neuroscience arena, peripheral nerve injuries continue to pose challenges for surgical reconstruction, as the clinical outcomes still appear unsatisfactory. 6 , 7 Advances in this field will require accurate measures of treatment effectiveness to assess new treatments that are certainly on the horizon.

The assessment of recovery after peripheral nerve surgery remains a challenging process to therapists and surgeons. Numerous cellular and biochemical mechanisms that occur in peripheral and central nervous systems affect the outcomes and result in difficult evaluation of recovery. 9 Measurement instruments for peripheral nerve surgery need to aid clinical diagnosis, assess and compare surgical repair techniques, track rehabilitation progress, provide feedback to both patient and therapist, as well as ascertain disability after injury. 9 The list of objectives useful in evaluation of hand function after peripheral nerve repair is provided in Table 1 . Outcomes research after nerve injury recently emphasizes more on functional results and patient-reported outcomes. 10 - 13 This review focuses on the scope of outcomes assessment tools and the current choices of measurements in outcomes research of peripheral nerve surgery. Table 2 details available methods for assessing patient outcomes after peripheral nerve surgeries.

List of Objectives to Evaluate Hand Function after Peripheral Nerve Repair *

Outcomes Assessment Tools for Measuring Outcomes after Peripheral Nerve Surgeries

Outcomes Assessment

Outcomes assessment in peripheral nerve injuries can be broadly categorized into tests of sensory function, motor function, pain and discomfort, neurophysiological and patient-reported outcomes.

Sensory function

Sensory tests indicate the sensory acuity of the hand and how well the patient is able to use it. 14 Semmes-Weinstein monofilament test is used to assess perception of cutaneous pressure threshold, which reflect reinnervation of peripheral targets. 15 Compared with using a common tuning fork, the test provides quantitative data that can be used to follow a patient serially during the course of nerve regeneration. 16 Tactile gnosis is the capability of the hand to recognize the character of objects, such as shapes, textures, and is a prime marker of functional recovery. 17

Two-point discrimination (2-PD) is an established assessment tool for tactile gnosis. 17 The static two-point discrimination test (S2-PD) measures the innervation density of the slowly-adapting receptor (fire continuously as long as pressure is applied) population. 14 One study showed an age-related decline in the ability to discriminate two points and there was no significant difference between men and women. 18 The moving two-point discrimination test (M2-PD) relies on the quickly-adapting receptor system (fire at onset and offset of stimulation), which recover sooner and in larger numbers. 19 The threshold values are lower than those of the static test. 20 2-PD outcome in nerve repair studies, however, is reported to be extremely variable, because there is a lack of standardization of the technique and the test is probably performed in different ways by different authors. 21 It is a serious problem because the test is frequently used to compare different nerve repair techniques. Therefore, when 2PD results are reported in a study, a detailed and referenced description, especially the pressure applied and the testing protocol should be mandatory. 21 Dellon has introduced a Pressure-Specifying Sensory Device (PSD) to provide a standardized pressure, however it may be difficult to use this technique in routine clinical practice. 22 2PD test is not recommended as the only instrument to monitor sensory function. Localization of touch, and identification based on active touching are also recommended to be assessed for an over-all evaluation of sensory function. 21 Other functional sensory tests include shape, texture identification, 23 , 24 vibration, and temperature perception, sharp and dull discrimination, and thickness discrimination. 25 , 26 These tests are timed and the results are converted into scores in multiple ways. 23 - 26

Medical Research Council scale , published in 1954, 27 is commonly used, by including 2-PD for grading the sensory outcome after peripheral nerve surgery. 17 , 23 , 28 This scale is categorized into S0-S4: S0 is the absence of sensibility; S1 is the recovery of deep cutaneous pain; S2 is the return of superficial cutaneous pain and some degree of tactile sensibility; S3 is the return of superficial cutaneous pain and tactile sensibility without over response; and S4 is the complete recovery. 23 This scale has also been criticized because it is based on subjective findings and vague nonstandardized data. It is recommended to be used with additional evaluation of motor recovery and pain. 23 Moberg proposed the pick-up test as an objective method to measure integrated function of the hand by scoring both the speed and accuracy of identification of the test objects. 24 , 29

Finger dexterity

The Sollerman hand function test consists of 20 activities that replicate the main hand grips in daily living, and is used to evaluate the quality of basic grip types. 30 Each subtest is scored depending on the quality of the hand grip and patient’s difficulty in performing the task. 9 This test can reflect integrated sensory and motor functions. 9

Motor function

Manual muscle testing (MMT) is used to assess motor innervation using British Medical Research Council muscle strength grading . 31 It can be conducted to assess larger muscles or muscle groups as well as intrinsic muscles of the hand. For median nerve, palmar abduction in the thumb is evaluated. For ulnar nerve, abduction in index, small finger, and adduction in small finger are tested. 23 , 31 Brandsma made some modifications to the MRC grades definitions, which were defined by range of motion and resistance, and made it more practical for intrinsic muscles of the hand. 31 Assessment of grip strength with dynamometry is a most common method of reporting motor outcome. 32 Power grip requires synergistic function of intrinsic and extrinsic muscles of the hand, so it is difficult to determine muscle dysfunction in isolation with this test. 4 It is also influenced by pain or increased sensitivity to pressure over the pillar region or scar, and should not be used where tissue healing is incomplete and testing would cause pain. 32 Pinch strength tests include key pinch, tip pinch and tripod pinch. Tip pinch and tripod pinch dynamometry more specifically target the thenar musculature and appears to be more responsive for assessing motor function after carpal tunnel release, compared with grip and key pinch strength test. 32

Pain and discomfort

Pain is associated with disability in patients after peripheral nerve injury. 33 The evaluation of pain will always be a self-report by patients. Numerical Rating Scale (NRS) for pain and Pain Visual Analog Scale (PVAS) are used to determine pain intensity and are easy to use. However, there are some deficiencies about these measurements. 34 First, it assumes that pain is a linear continuous phenomenon, which is not tenable in most cases. Second, all patients cannot respond to these scales in a uniform manner, because of the high variability in the pain they experience. 34 McGill Pain Questionnaire is a multidimensional pain scale which provides much more information on dimensions of pain beyond the simple factor of intensity, such as sensory components (tingling and hypersensitivity) as well as affective responses to pain. 33 - 36 However, it is a long questionnaire and imposes a larger burden on patients and might be less responsive than VAS. 34 The Pain Disability Index assesses the impact of pain on life domains. 33 It includes seven categories of life activity: family/ home responsibility, recreation, social activity, occupation, sexual behavior, self-care and life support activity. 37 Consistency, validity and reliability of this questionnaire were tested and proved to be useful in nerve injury studies. 33 In patients with chronic nerve injury, pain intensity is only one component of pain, and the impact of pain in the disability should also be considered. 33 A clear understanding of the goal of the research question will help determine which measurement is appropriate.

Cold sensitivity is a complex symptom, which may present as pain, numbness, stiffness, weakness, swelling and change in skin color. The Cold Sensitivity Severity Scale (CSS) is used to evaluate sensitivity of cold intolerance during daily life. 38 Potential Work-Exposure Scale assesses exposure in the work place. 38 The CSS scale, in conjunction with Potential Work-Exposure Scale can be used to predict the likelihood of the patient’s return to pre-injury employment. 39 The reliability and validity of these two questionnaires have been demonstrated in the development phase and in other studies. 38 , 39 The Cold Intolerance Symptom Severity questionnaire is a reliable and valid measurement with the threshold value for pathological cold intolerance of 30 40 and 50 for population with Scandinavian climate. 41

Neurophysiological outcome measurements

Neurophysiological examinations include electroneurography (ENG), also known as nerve conduction studies (including sensory nerve conduction velocity and amplitude, motor nerve velocity, distal motor latency), and electromyography (EMG). They measure the electrical activity of muscles and nerves, and are the primary studies used to gain information on the location, number, and pathophysiology of lesions affecting the peripheral nerve. 42 In evaluation of carpal tunnel syndrome (CTS), distal motor latency (DML) and sensory nerve conduction velocity (SCV) are often performed. American Association of Electrodiagnostic Medicine, American Academy of Neurology, and the American Academy of Physical Medicine and Rehabilitation published the parameters for performing CTS electrodiagostic (EDX) testing to address the best EDX studies to confirm the diagnosis and guide clinical researches. 43 Studies of ENG in CTS patients have presented contradictory results between neurophysiological findings, patient symptoms and clinical improvements. 44 - 47 However, they did not refute the necessity of conducting ENG when evaluating patients with CTS. 44 - 47 Grading scales for the neurophysiological changes of median nerve entrapment were also introduced to facilitate comparison of the severity of the disease. 47 , 48 A study showed that both ENG and patient-oriented questionnaires were highly responsive to treatment of CTS, but no correlation was observed between them. Therefore both outcome measurements are recommended to provide a multifaceted assessment. 49 ENG test can also be used to evaluate outcomes of nerve grafting, 50 nerve repair, 25 and cubital tunnel syndrome. 51 , 52 Patients showed continued improvement in sensory and motor nerve conduction velocity even beyond 2 years in cubital tunnel syndrome. 51 In brachial plexus injury, EMG is commonly used to evaluate muscle reinnervation. 53

Patient reported outcomes

There is a shift towards using patient-reported outcome with valid and reliable measurement tools in hand surgery. In a systematic review of hand surgery outcomes studies, quality of life outcomes were reported in 31% of the studies, comprising of symptoms, patient satisfaction, and time to return to work and data from quality-of-life-related questionnaires. 2 Questionnaires commonly used in peripheral nerve surgery outcome studies include Short Form 36, Disability of the Arm, Shoulder and Hand (DASH), Boston Carpal Tunnel questionnaire (BQ or CTQ), the Michigan Hand Outcomes Questionnaire (MHQ), Stothard and Kamath questionnaire.

The Short Form- 36 (SF-36) is a validated measure for patient’s functional health and quality of life, to assess the extent to which a patient’s day-to-day life is affected by their health. 54 It includes 8 domains: physical functioning, social functioning, role limitations due to physical functioning, role limitations due to emotional problems, energy and vitality, mental health, bodily pain, and general perception of health. 55 Although a general health assessment questionnaire and not sensitive enough to evaluate regional conditions, 13 SF-36 is used in combination with other region specific questionnaires to evaluate peripheral nerve injury. In Novak’s study, SF-36 bodily pain is proved to be a predictor of the DASH score, indicating that long-term disability in patients after nerve injury can be predicted by more pain. 10 Other studies used SF-36 to evaluate functional outcome by assessing quality of life. 11 , 54

DASH questionnaire is designed to measure disability for any region of the upper extremity and can be used for single or multiple disorders. 56 It consists of 30 core questions and an optional additional 8 questions assessing work, sports and performing arts activities, with a higher score indicating more disability. 56 The DASH score is a subjective instrument to estimate the patient’s view of disability. 57 It is used for evaluation of brachial plexus surgery, 11 , 58 , 59 nerve transfer, peripheral neuromas surgery, 60 nerve repair, 11 carpal tunnel release, 61 and ulnar nerve transposition. 62 The QuickDASH was developed in 2005 to minimize time and responder burden. 63 It demonstrated reliability, validity and responsiveness when used for patients with either a proximal or distal disorder of the upper extremity. Compared to DASH, it is a more efficient version and retains its measurement properties. 63

Boston carpal tunnel questionnaire (Levine and Katz questionnaire) is a self-administered questionnaire for the assessment of severity of symptoms and functional status in patients who have carpal tunnel syndrome. 64 It consists of symptom severity and functional status subscales. The first scale includes 11 questions of pain, altered sensibility and weakness. The second assesses the patient’s self-reported ability to perform 8 tasks. 56 It is proved to be useful in quantifying severity of symptoms and functional state of patients before and after surgery. But it was not possible to predict the outcome results in CTS from the preoperative scores because there was no statistically significant relationship between them. 65 A study indicates that BQ score at 2 weeks is a reliable, responsive and practical instrument for outcome measure in carpal tunnel surgery, and it is equivalent to 6 months postoperative score. 66 The questionnaire has also been used to identify potential prognostic factors influencing outcome, 47 and predictor of scar pain after carpal tunnel release. 67 In relation with objective measurements, both scales had a positive, but modest or weak correlations with 2-PD and Semmes-Weinstein monofilament testing, 64 and no relation with nerve conduction studies pre and postoperatively. 65 , 68 , 69 Some authors recommend that BQ and nerve conduction data should be used together to monitor CTS patients. 65

The Michigan Hand Outcomes Questionnaire (MHQ) is a 37-item self-assessment instrument that measures disability along 6 domains: function, activities of daily living, pain, hand appearance, patient satisfaction, and work disability. 70 It is used to assess different hand disorders, including carpal tunnel syndrome (CTS). In assessing CTS, the MHQ is more specific than the DASH, because it has questions only relating to the hand, and can measure symptom and function separately. It is more versatile than BQ but also less specific, because questions relating to pain are not phrased explicitly for CTS, such as tingling and numbness. MHQ may be more useful when independent score from multiple domains are required or when comparison with an unaffected control hand is needed. A study also revealed that the MHQ might be more sensitive to functional changes; the DASH seems more correlated with disability days. 71

Because of the complexities of neurophysiology, assessment of recovery after peripheral nerve surgery remains a complex process to therapists and surgeons. A combination of tests, which correlate with neurophysiological parameters and integrated hand function, are required to provide a valid, reproducible and comprehensive assessment of outcomes. Measurement instruments for peripheral nerve surgery generally include sensory tests, motor function tests, integrated hand function tests, pain and discomfort assessments, neurophysiological outcome measurements, and patient reported outcomes. With a plethora of tests to choose from, researchers need to focus on measurements best relevant to specific conditions and research questions. These data will help researchers have a better understanding of the recovery process and provide the best possible outcomes for the patients.

• Outcomes assessment tools and the current choices of measurements in outcomes research of peripheral nerve surgery
• Several aspects relating to function, pain, and patient perception of outcomes are evaluated after peripheral nerve repair
• Choice of specific measures depend on the researchers’ interest and the disease or treatment under investigation

Acknowledgments

Supported in part by a Midcareer Investigator Award in Patient-Oriented Research (K24 AR053120) from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (to Dr Kevin C. Chung).

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