The reliability of the modified Manual Muscle Test for persons with MS

The reliability of the modified Manual Muscle Test for persons with MS | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The reliability of the modified Manual Muscle Test for persons with MS Nico Arie Van der Maas, Regula Steinlin Egli, Deborah R. Vogt, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7576603/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Multiple sclerosis (MS) presents various symptoms, such as weakness, spasticity, ataxia, and reduction in sensory function. Traditional manual muscle strength tests may be biased due to the influence of spasticity. The modified Manual Muscle Test (mMMT) for people with MS (pwMS) was developed to take spasticity into consideration. This study aimed to evaluate the intra- and interrater reliability of the mMMT, as well as the influence of fatigue and spasticity on test results. Methods Six raters examined 28 pwMS in this single-centre, prospective, cross-sectional, and longitudinal study with a test-retest design. The muscle strength tests for dorsal foot flexion, hip flexion, and elbow flexion were used. Testing and retesting were conducted within 4 hours. Fatigue was assessed using the Fatigue Scale for Motor and Cognitive Functions and a numeric rating scale. Spasticity was evaluated using the Modified Tardieu Scale. The interrater reliability of the mMMT was evaluated by the intraclass correlation coefficient using one-way random effects ANOVA models. The intrarater reliability was estimated using two-way random effects ANOVA models. Models were adjusted for spasticity and rating order as a proxy for fatigue. Results The interrater reliability of the mMMT was poor. The results varied between raters and muscle groups. However, the intrarater reliability was good (overall intraclass correlation coefficient, 0.77). Fatigue or spasticity did not affect the test results. Conclusion The mMMT may be a reliable measure of muscle function in MS when applied by the same healthcare professional. We cautiously conclude that it may be possible to test selective muscle function in the presence of spasticity, reducing its influence on muscle strength testing in pwMS. This study also highlights the importance of rater training and the development of test protocols for each muscle group separately. Trial Registration ClinicalTrials.gov ID NCT03603691. Initial registration date 06/19/2018. Multiple sclerosis Manual muscle test Reliability Fatigue Spasticity Physiotherapy Figures Figure 1 Figure 2 Figure 3 1. Introduction Many persons with multiple sclerosis (pwMS) undergo physiotherapy due to motor function impairment, a common symptom in multiple sclerosis (MS). Especially in the progressive course of the disease, motor dysfunction is a major contributor to reduced mobility and quality of life ( 3 , 30 ). Improving motor dysfunction is therefore an important goal of physiotherapy. Over 60% of pwMS with moderate to severe MS require treatment for spasticity, its associated problems, or both ( 5 , 6 , 14 , 17 , 44 ). Spasticity, as well as ataxia, muscle weakness, fatigue, and sensory impairment pose challenges to the treatment and measurement of muscle dysfunction. Muscle function tests can be confounded by these factors, which are not considered by currently available tests including handheld dynamometer and isokinetic dynamometry tests. Although some authors advise against using manual muscle testing to test spastic muscles ( 49 ) or to diagnose muscle weakness ( 8 ), it is still the most widely used muscle test in neurology, as the classic British Medical Research Council (BMRC) Scale Manual Muscle Test ( 20 , 42 ) with 6 grades is part of the EDSS ( 17 , 37 , 40 ). A manual muscle test has favourable characteristics (quick test, always available and known by most health care professionals) but has the uncertainty of the amount of resistance to be applied when the test is performed with manual resistance. Spastic movement disorders have recently been defined as disordered sensorimotor control resulting from upper motor neuron lesions and presenting as intermittent or sustained involuntary muscle activation. It is characterised by reduced ability to selectively activate muscles with significant co-activation of antagonist muscles ( 48 ). In spasticity, the activation of antagonists and synergists of the targeted muscle group may occur during muscle function testing, resulting in a deviation of movement or an increase in muscle tone. Thus, manual muscle tests may not only assess the targeted group of muscles but also interference from antagonists and agonists. Therefore, we may not selectively test the strength of specific muscles and currently available tests might be biased. What can be done to improve muscle testing when a spastic movement disorder is present in pwMS? Posture ( 27 , 31 ), sensory input ( 48 ), and movement speed ( 41 , 43 ) are known to influence spasticity. The modified Manual Muscle Test (mMMT) uses these factors to take spasticity during muscle strength testing into account. It is a novel muscle test for pwMS. ( 60 , 61 ). By defining the exact body posture und position of the muscle groups over a specific joint while testing (test position), the acceptable change in the test position, and the sensory input, the influence of spasticity on the test results is minimised (Appendix A). The precise criteria for test conditions and performance describe an acceptable muscle response to manual resistance without discernible spasticity. These criteria are particularly important as the mMMT uses the 'break' test ( 52 , 68 ) to achieve maximum performance but increases the risk of enhanced spasticity, which is undesirable. The mMMT is an isometric muscle test with 12 grades, that is easy to perform even in people with a complex neurological condition such as MS. The test criteria also describe how long a position should be maintained in grade 2 and above. With its 12 grades, the mMMT can describe smaller differences in muscle function than the most commonly used test in MS, the BMRC manual muscle test, which has six grades. Any muscle function test used to measure changes due to physiotherapy interventions must reliably assess muscles. Of the muscles typically affected in MS, the tibialis anterior muscle is often the first and worst affected muscle ( 2 ). It is significantly weaker in pwMS than in their sex-matched controls ( 45 , 69 ). The gastroc-soleus muscle group is most affected by spasticity in pwMS ( 46 ). These muscles and the dorsal flexors are antagonists that can present weakness, spasticity, loss of reciprocal inhibition, and hyperexcitability ( 34 , 46 , 47 ). This constellation is a typical example for muscle testing, in which spasticity may influence, and potentially bias, the results if the test position and execution favour an increase in spasticity. Therefore, testing the muscle strength of the dorsal flexors is an effective way to determine whether the mMMT can measure muscle strength in the presence of spasticity without being affected by it. Furthermore, they are exemplary muscle groups that cause walking problems in pwMS ( 28 , 46 , 67 , 69 ) which underscores the importance of an unbiased and reliable testing. Further, we choose the manual muscle test of the dorsal flexors as the focus, as can be seen in the inclusion criteria of this study. The hip flexors are another muscle group that shows weakness in pwMS and are important for walking ( 23 , 45 ). In the presence of spasticity in the tested extremity, this test may produce biased results, as an increase in spasticity during testing may cause the test position to deviate and alter the results. Therefore, we also included hip flexors. A 'break' test for the upper limb muscles poses a much higher risk of injury to the shoulder joint and muscles if these muscles are weak and unable to stabilize the scapula and shoulder joint. This is particularly true when testing an older population, where problems with the rotator cuff muscles are common. Testing elbow flexion when the upper arm is stabilized against the trunk does not pose such a high risk. As spasticity in the elbow flexors is common in people with pwMS, we have chosen to test the elbow flexors, representing the upper extremities muscle groups. Each participant would be tested multiple times. Interventions with high physical demands, as in this study, may increase the fatigue in pwMS ( 12 , 56 ). A significant relationship has been reported between perceived fatigue and fatigability in MS, such that pwMS who reported elevated fatigue are also highly fatigable ( 39 ) and exhibit greater reductions in muscle strength and voluntary muscle activation ( 10 ). Therefore, we hypothesised that fatigue could potentially increase with increasing number of tests performed and included fatigue test as a covariate in the statistical model. Tonic dorsiflexion inhibits the activity of the calf muscles in healthy individuals ( 13 ). Also, Shindo et al ( 58 ) found that in healthy individuals the increase of reciprocal inhibition of the soleus nerve was positively correlated to the strength of the dorsiflexion. In the case of MS, if the reciprocal inhibition is still intact, weak dorsiflexors causes less inhibition. An increase in muscle tone resp. spasticity due to multiple testing and the use of the 'break' test principle could also be expected. Performing a maximal test in a region of the body with a higher level of spasticity could cause greater movement deviation during testing and result in a lower test score in the later tests. This would alter the inter- and intrarater reliability of the test. We considered this to be a major problem in the trial, so we assessed the effect of multiple testing on spasticity and took steps to address this issue. To reduce the risk of testing induced spasticity, pwMS were given a break of at least 10 minutes between tests to allow them to rest. In addition, an hour break was planned between the test and retest series. The aim of this study was to evaluate the inter- and intrarater reliability of the mMMT for dorsal flexion of the foot and hip and elbow flexion in pwMS. Furthermore, we evaluated the influence of fatigue and spasticity on the reliability of the test results. 2. Methods 2.1. Study design and ethical considerations This single-centre, prospective, cross-sectional study was carried out as a test-retest within 4 h at the University Hospital for Geriatric Medicine and Rehabilitation Felix Platter, Basel. This study was conducted in accordance with the Declaration of Helsinki, the Human Research Act of Switzerland (HRA) and Ordinance on Clinical Trials (ClinO), and was approved by the Swiss Ethics Board of Northwest and Central Switzerland (project-ID 2018-01103). All participants provided informed consent before participation. The primary objective was to show that the mMMT has a high interrater reliability, defined as an intra-class correlation coefficient (ICC) of at least 0.7 (prespecified ICC margin) (33, 58). The null hypothesis was that the lower limit of the 95% confidence interval (CI) of the ICC is smaller or equal to the ICC margin. All participants were assessed twice (at the test and retest stages) by six raters, three experienced neurologists and three MS-specialised physiotherapists (see Appendix B). Three raters used the mMMT and the other three used the BMRC manual muscle test of the Neurostatus EDSS (17, 32, 40) (these results will be reported elsewhere). Raters assessed the three muscle groups (dorsal flexion of the foot, and hip and elbow flexion) on the left and right side. The raters were allocated to study participants in random order and were blinded to the ratings of the other raters. pwMS were given a break of at least 10 minutes between tests. Between test and retest sessions, the participants were given an hour break to relax. We considered increasing spasticity to be the most important confounder. Assuming that participants with higher levels of spasticity in the tested limb would have a higher risk of increasing spasticity over time, we repeated the primary analyses for subgroups of patients with high and low spasticity to assess the influence of increasing spasticity on interrater reliability. The Modified Tardieu Scale (MTS) (23, 27, 39) was used to determine the degree of spasticity and to define high and low spasticity (MTS score 3 or 4 and 0 or 1, respectively). To account for confounding by increasing fatigue, the primary analysis was repeated with the order of the ratings included as covariate in the statistical model. This approximation was used since patients’ self-assessment of fatigue via NRS was only done at baseline (before performing the first muscle test) and at the end of the examinations (after performing the last muscle test). The secondary objective was to examine the intrarater reliability of the mMMT. using a test – retest procedure. We also examined the association of the mMMT with self-reported fatigue and spasticity, and test time for the test-retest results as covariates in the statistical model. To assess the relation between the test-retest results of the mMMT and fatigue and spasticity resp., we used a 11-point fatigue Numerical Rating Scale (NRS) (23, 70) and MTS scores resp. that we administered before muscle testing started and after the last mMMT retest. These associations were examined exploratively by plotting test and retest ratings against the fatigue NRS respectively modified Tardieu scale. We evaluated the influence of the test time, i.e., the number of hours since the start of the test day, on fatigue and spasticity. We expected that this would be useful as a surrogate measure of participants fatigue and spasticity and, hence, could be related to the mMMT scores. The relations between the mMMT and testing time was investigated exploratively. The study was approved by the Ethics Board of Northwest and Central Switzerland (ID: 2018-01103) and pre-registered at ClinicalTrials.gov (ID: NCT03603691). All participants provided a written informed consent. Two training sessions were held to familiarise the experienced accessors with the use of the mMMT. 2.2. Study population Participants were diagnosed with MS according to the McDonald criteria (64), had an EDSS of between 0 and 6.5, and were older than 18 years. We enrolled persons with mMMT scores 2+ to 4+ or Neurostatus manual muscle scores between 2 and 5 for the dorsal flexion muscles tests of the foot. As previously discussed, the gastroc-soleus muscle group is most affected by spasticity in pwMS (46) and the tibialis anterior muscle is often the first and most affected muscle in pwMS (2). By defining these muscle scores as inclusion criteria, we ensured, that muscle weakness and/or spasticity would be present in the study population, and that using the mMMT testing method that minimises the influence of spasticity would make sense. Exclusion criteria were an acute MS episode within three months prior to testing, severe cognitive changes or distinct fatigue that made it impossible to perform the experiment for four hours, and current back, neck, or elbow pain. Participants were recruited from MS specialised physiotherapy institutions and hospitals (Appendix B). 2.3. Other outcome measures We used the Fatigue Scale for Motor and Cognitive Functions (FSMC) questionnaire (51) to quantify MS-related fatigue and decide whether the pwMS could be included in the study, i.e. the pwMS did not have distinct fatigue, defined as an FSMC motor score => 27. The pwMS completed the FSMC questionnaire prior to inclusion in the study. 2.4. Statistical analysis Sample size was estimated using a resampling approach (Appendix C). Allowing for a drop-out rate of 10%, 28 pwMS were required to have at least 80% power to detect a clinically relevant intraclass correlation coefficient (ICC) of > 0.70 (35) for the mMMT results, based on a 95% confidence interval (CI). All analyses were preplanned in a statistical report and analysis plan and conducted using the R statistical software packages (53), based on available data from all 28 included pwMS. Reported confidence intervals were not adjusted for multiple testing. The mMMT interrater reliability was assessed by the ICC based on a one-way random effects ANOVA model, considering an absolute agreement (R package ‘’psych’’). The ICC was calculated for each mMMT item separately, for each mMMT muscle group separately, and for the overall mMMT score. Analyses were adjusted for fatigue by including the rating order as covariate. The analysis was repeated separately for subgroups of participants with high (MTS baseline score ≥ 3) and low (MTS baseline score ≤ 1) spasticity in the foot (high spasticity scores were not observed in other muscle groups). For the overall mMMT score, foot spasticity was used as a reference. The mMMT intrarater reliability was first estimated for each rater separately, using two-way random-effects ANOVA models, considering absolute agreement. Then, a pooled estimate was derived by combining all ratings and including raters as a covariate. Associations of the mMMT score with fatigue and spasticity were examined exploratively by plotting test and retest ratings against fatigue NRS and MTS scores, respectively. We further examined the overall association with linear mixed-effects model for each test separately. The models included the mMMT score as the dependent variable, the corresponding fatigue NRS rating or MTS groups (continuous variable) and test type (test or retest) as independent variables (fixed effects), and participant and rater as random effects (random intercepts). We also investigated the interaction of NRS and MTS scores with the test type. The relationship of the mMMT score with testing time was investigated exploratively using line plots. 3. Results The study participants were all recruited by physiotherapists and were receiving physiotherapy. They were older, had been affected by MS longer and had higher EDSS scores than the population of pwMS receiving physiotherapy in the Swiss MS Registry (Table 1). The study participants were also older and had been affected longer than the pwMS in physiotherapy treatment of the plausibly representative Swiss March study (38) and of the representative studies of the Multiple Sclerosis Questionnaire for Physiotherapists (MSQPT) (65, 66). Therefore, the mMMT study is not representative of the Swiss pwMS population receiving physiotherapy. Table 1 Demographic data. mMMT Swiss MS Registry* Female (%) 68 73 Age (mean, years) 60 52 n 27 693 Years of illness (mean) 21 13 EDSS 0–3.5 (%) 25.0 45.3** EDSS 4–6.5 (%) 75.0 25.1** EDSS 7–9.5 (%) 0.0 13.1** *Persons with MS regularly using physiotherapy (20). ** An EDSS proxy, estimated based on self-reported walking distances. Abbreviations: EDSS, Expanded Disability Status Scale; mMMT, modified Manual Muscle Test; MS, multiple sclerosis. Participants were tested with the FSMC prior to enrolment to determine their motor fatigue, and 21 out of 28 pwMS had severe motor fatigue. One pwMS withdrew after five manual muscle tests due to hip pain, one FSMC was missing after testing and 0.51% of MTS values were missing. Before testing, the MTS test for the calf muscles (both sides) showed 16 tests without spasticity (MTS 0), 6 tests with discrete spasticity (MTS 1), 16 tests with a moderate spasticity (MTS 2) and 17 tests with a high level of spasticity (MTS 3 and 4). The other muscle groups showed discrete to moderate spasticity in 26 tests and no tests with a high level of spasticity. 1 MTS result was missing. After the mMMT retests, the MTS test for the calf muscles showed fewer tests without (10), more tests with discrete (15) or moderate (18) spasticity, and fewer tests with high levels of spasticity (13). 3.1. Interrater reliability of the mMMT The targeted prespecified ICC margin of 0.7 was not reached for any of the assessed levels (Table 2). The overall ICC was rather poor. The highest ICC values were observed on the left body side. There was high rating variability for most pwMS. Only a few pwMS received the same rating from all three assessors. It also appeared that certain raters tended to give generally low or high ratings. Table 2 ICCs and 95% confidence intervals for interrater reliability of the overall mMMT score, for each muscle group, and for each body side per muscle group. Level ICC [95% CI] Overall 0.30 [0.07, 0.54] Foot 0.39 [0.16, 0.62] Foot left 0.64 [0.45, 0.80] Foot right 0.48 [0.26, 0.69] Hip 0.36 [0.13, 0.59] Hip left 0.64 [0.44, 0.80] Hip right 0.29 [0.06, 0.54] Elbow 0.32 [0.09, 0.56] Elbow left 0.63 [0.43, 0.79] Elbow right 0.00 [-0.18, 0.25] Abbreviations: CI, confidence interval; ICC, intraclass correlation coefficient. Adjusting for test order did not change the ICC estimates of interrater reliability (Table 3). This suggests that there was no general association between ratings and potential fatigue. Table 3 ICCs and 95% confidence intervals for interrater reliability adjusted for fatigue by test order. Level ICC [95% CI] Overall 0.29 [0.06, 0.53] Foot 0.38 [0.10, 0.61] Foot left 0.64 [0.41, 0.79] Foot right 0.48 [0.21, 0.68] Hip 0.35 [0.11, 0.57] Hip left 0.63 [0.43, 0.78] Hip right 0.29 [0.00, 0.53] Elbow 0.32 [0.03, 0.56] Elbow left 0.62 [0.40, 0.78] Elbow right 0.00 [0.00, 0.24] Abbreviations: CI, confidence interval; ICC, intraclass correlation coefficient. High levels of spasticity were only observed in the foot (Table 4). Therefore, the spasticity subgroup analysis was only performed for the mMMTs foot (each body side separately and pooled) and for the mMMT overall. For the mMMT overall the spasticity subgroups of the foot pooled were used. We found no evidence that interrater reliability differed between pwMS with high and low spasticity scores in the foot (Table 4). The pooled data for both feet show that the mean ICC for pwMS with low spasticity scores is lower than for pwMS with high spasticity scores; however, the 95% confidence intervals largely overlap. Table 4 ICC and 95% confidence intervals for subgroups with high and low spasticity scores. Level low spasticity score high spasticity score Overall 0.33 [-0.01, 0.70] 0.29 [-0.06, 0.69] Foot 0.22 [-0.11, 0.62] 0.50 [0.13, 0.80] Foot left 0.59 [0.23, 0.86] 0.57 [0.18, 0.86] Foot right 0.56 [0.19, 0.85] 0.51 [0.13, 0.83] Abbreviations: CI, confidence interval; ICC, intraclass correlation coefficient. 3.2. Intrarater reliability of the mMMT The mMMT intrarater reliability was good. However, there was a considerable variability between raters (Table 5). Looking at different muscle groups, the intrarater reliability was highest for the foot, followed by the hip and elbow. The pooled overall value was 0.77, which exceeded the 0.75 limit for good reliability (33 ,58). Table 5 Intrarater reliability of the modified Manual Muscle Test (mMMT). Level Rater 1 Rater 2 Rater 3 Rater 4 Rater 5 Rater 6 Pooled Overall 0.61 [0.12, 0.86] 0.68 [0.10, 0.90] 0.84 [0.58, 0.94] 0.90 [0.72, 0.96] 0.97 [0.88, 0.99] 0.97 [0.92, 0.99] 0.77 [0.65, 0.86] Foot 0.64 [0.20, 0.87] 0.75 [0.33, 0.92] 0.74 [0.38, 0.91] 0.85 [0.61, 0.95] 0.98 [0.90, 0.99] 0.97 [0.91, 0.99] 0.75 [0.62, 0.84] Foot left 0.73 [0.36, 0.90] 0.70 [0.27, 0.89] 0.84 [0.58, 0.94] 0.90 [0.73, 0.97] 0.95 [0.76, 0.99] 0.99 [0.96, 1.00] 0.80 [0.67, 0.88] Foot right 0.40 [-0.11, 0.75] 0.87 [0.64, 0.95] 0.77 [0.44, 0.92] 0.91 [0.75, 0.97] 0.99 [0.97, 1.00] 0.98 [0.93, 0.99] 0.76 [0.63, 0.85] Hip 0.43 [-0.05, 0.77] 0.74 [0.28, 0.91] 0.69 [0.30, 0.89] 0.72 [0.35, 0.90] 0.92 [0.73, 0.98] 0.87 [0.66, 0.95] 0.70 [0.53, 0.81] Hip left 0.33 [-0.16, 0.71] 0.72 [0.34, 0.90] 0.84 [0.59, 0.95] 0.89 [0.71, 0.96] 0.96 [0.86, 0.99] 0.89 [0.73, 0.96] 0.76 [0.61, 0.86] Hip right 0.58 [0.11, 0.84] 0.68 [0.21, 0.89] 0.58 [0.10, 0.84] 0.68 [0.27, 0.88] 0.90 [0.69, 0.97] 0.75 [0.42, 0.90] 0.59 [0.42, 0.74] Elbow 0.55 [0.01, 0.84] 0.65 [0.23, 0.87] 0.93 [0.79, 0.98] 0.88 [0.68, 0.96] 1.00 [1.00, 1.00] 0.96 [0.89, 0.98] 0.66 [0.47, 0.78] Elbow left 0.76 [0.40, 0.92] 0.84 [0.59, 0.95] 0.92 [0.78, 0.97] 1.00 [1.00, 1.00] 1.00 [1.00, 1.00] 0.98 [0.94, 0.99] 0.81 [0.69, 0.89] Elbow right 0.42 [-0.10, 0.77] 0.06 [-0.40, 0.54] 0.54 [0.08, 0.82] 0.33 [-0.21, 0.72] 1.00 [1.00, 1.00] 0.77 [0.47, 0.91] 0.22 [0.06, 0.39] Test-retest intraclass correlation coefficients with 95% confidence intervals are reported for each rater separately and pooled for all raters. 3.3. Associations between the mMMT score and fatigue The relationships of the overall mMMT results with fatigue (NRS) are shown in figure 1. The relationships between the overall mMMT score and the overall spasticity (MTS) scores, and between the mMMT foot score and the spasticity foot score for test and retest are shown in figure 2 resp. figure 3. None of these figures indicate an association of the mMMT with fatigue or spasticity. Also, when investigating these relationships further with linear mixed-effects models, including random intercepts for rater and patient, we found no statistical evidence for an association. (Appendix D). In conclusion, our data do not provide evidence that the mMMT results are influenced by fatigue or spasticity. 3.4. Associations between the mMMT score and testing time We have also evaluated the influence of the test time, i.e., the number of hours since the start of the test day, on fatigue and spasticity. We expected that this would be useful as a surrogate measure of participants fatigue and spasticity and, hence, could be related to the mMMT scores. However, based on a visual inspection of the plots, no overall relationship was apparent (Appendix E). 4. Discussion The main findings of this study are that the mMMT can be a reliable outcome measure for muscle function if performed by the same medical professional treating the pwMS, that fatigue does not affect test reliability, and that the spasticity degree does not affect the mMMT score. With these characteristics, the mMMT can be a valuable measurement for evaluating the effects of exercises to enhance muscle function in the presence of spasticity. The inclusion criteria resulted in a study population that was older, had a higher mean number of years of disease, and predominantly had an EDSS between 4 and 6 compared to the Swiss MS registry population using physiotherapy (21). Considering that only 44% of the pwMS in Switzerland receiving physiotherapy (4), the population of this study was not representative of the Swiss MS population nor of the Swiss MS population using physiotherapy. This can be explained by the inclusion criteria of the manual muscle test score between 2 and 5 for the dorsal flexors of the foot. This criterion was designed to ensure that the population has weakness and its associated spasticity in the lower limb, so that testing with the mMMT would be meaningful, as the mMMT takes spasticity into account when testing. The results show that this criterion was sufficient to ensure spasticity in the calf muscles as only 10 of 56 tests did not show spasticity after the retests. Spasticity is directly correlated with disease progression (1): pwMS in the early stages of their disease rarely have spasticity, whereas for the more progressed pwMS spasticity is more likely. Therefore, it was to be expected that our population would be more severely affected by MS than the general MS population in Switzerland. Does that influence our conclusions or the generalisation of our results? One could argue that a manual muscle test that takes spasticity into account would also work for muscles without spasticity. The mMMT for individuals without spasticity is a more complex test than a regular muscle test but given the same administration, the mMMT should produce similar results as another manual muscle test. If so, the mMMT could be used for pwMS with or without spasticity, but with an EDSS =<6.5, the highest EDSS score in our population. We conclude that the unrepresentative nature of the study population does not limit the conclusions of this study or the generalisability of its results. We found that mMMT interrater reliability was poor and that this study does not support its use in comparative studies. The mMMT has 4 grades against gravity, that are executed with manual resistance that needs to be judged to be a small to maximum resistance. A large number of grades against gravity (24) and subjectivity of judgement renders it difficult to achieve good reliability (8, 22). These factors surely might play a role, at least in the interrater reliability as the judgement of what is slight, moderate, high or maximum resistance might be different also between experienced raters, as in our study, in which certain raters tended to give generally low or high ratings, which influenced the interrater reliability. Several authors (7, 22, 24) stated that individual tester characteristics influence the test results for manual muscle tests, as also is the case for muscle tests using handheld dynamometry (36, 54, 62). Tester strength is one factor that can have an impact (63), even if participants are of low strength, as reported by Stone et al (62), who found that reliability can be compromised by inadequate muscle strength of the rater. Other individual factors that influence the test results may include a slightly different point and line of application and type of instruction, the tone of the tester's voice and the interaction between tester and patient (22), all of which can be standardised to some extent in tester training. The highly experienced testers received training on the application in two sessions, which may have been insufficient. Also, training the raters in the absence of people with spasticity may have played a role. In a follow-up study with adjusted standardizing of the mMMT (16), more intensive training of the 6 raters with persons presenting spasticity significantly improved interrater reliability (ICC 0.60-0.87), highlighting the importance of rater training in pwMS to achieve homogeneous mMMT reliability results. Another factor that could have influenced the test results, is the number of raters used to calculate inter-rater reliability. Often 2 raters are used to assess inter-rater reliability (11, 15, 19, 50). Knepler and Bohannon (33) found that 10 raters varied in the forces they applied for each MMT grade over 3. The variability of test results between raters tends to increase when more than 2 raters are used and, of course, when more grades above 3 are available, as in this study. This is also an uncomfortable tendency for our study, which again emphasises the importance of training raters in a day-to-day environment to ensure reliable test results. Using multiple raters in a reliability study can lead to more ecologically valid results and is recommended for reliability studies of manual muscle tests. The intrarater reliability of the mMMT (ICC>0.7) can be considered good according to Koo and Li (35) and Terwee at al. (63). The results of the three muscle function tests indicated that the intrarater reliability strongly depended on the muscle group tested, in line with the results of other studies (7,20, 55). The right elbow flexion showed unexpectedly poor reliability in our study, which negatively affected the overall reliability rating. In contrast, the left elbow tests showed good intra-rater reliability. Most reliability results favoured more or less the left side, indicating a difference in test reliability between the right and left sides of the body. This difference can only be explained by the tester’s different position on each side and the way in which the test was executed. These findings confirm the need to develop specific, standardised tests for each muscle group, with defined positions and executions for each side, as well as intensive training to achieve higher reliability. We did not evaluate the influence of fatigue on the test results individually. However, the data of the elbow test showed no indication that fatigue could explain this unexpectedly poor reliability. Manual muscle tests are an important tool to evaluate the results of exercise on the muscle function in the daily treatment of persons with MS. The mMMT intrarater reliability of this study indicates that it is a useful tool for testing muscle function, if executed by the same person, which is mostly the treating health care professional. An improvement of the intrarater reliability should be possible when the above-mentioned factors will be considered. Steinlin Egli (61) further standardised the mMMT per muscle group. A follow-up study with selected further standardised muscle groups (16) also showed a slight to substantial improvement in intra-rater reliability compared to this study. In the preparation of this study, we stipulated that executing multiple muscle tests in a population with motor fatigue could influence the reliability results and included pre- and post-testing of fatigue with the FSMC and numerical rating scale for fatigue. We found that our study cohort showed high levels of motor fatigue on the FSMC (score >=32 in 21 pwMS) and 18 pwMS with a worsening of the numerical rating scale for fatigue between 2 (n=4) and 6 (n=4) levels, a worsening we expected. Loy et al (36) reported a significant relationship between perceived fatigue and fatigability in pwMS, such that those reporting higher levels of fatigue are highly fatigable. Cognitive and motor fatigue may increase in pwMS during interventions with high physical demands (12, 56), as was the case in our study. Furthermore, motor fatigability might be closely related to motor symptoms in MS (57), leading to the assumption that increased fatigue might alter motor symptoms. Spiteri et al. (59) investigated effort-dependent and -independent components of fatigue in pwMS and concluded that effort might cause a reduction in activity in executive networks of specific brain regions. With this theoretical background, an influence of fatigue might be expected in the later tests. If fatigue played a role in our results, we did not find indications that an enhanced fatigue influenced any of the reliability measures even after performing multiple tests per pwMS. Adjusting the mMMT results for fatigue by test order did not change the ICC estimates. Severijns et al (57) found that a sustained maximal voluntary contraction of 15-180 s induced greater fatigability in pwMS than in healthy controls. The mMMT uses isometric contractions of 1-3 s. These contractions may have been too short to increase motor fatigue during the test. The reported reduced ability to activate muscles following maximal effort-fatiguing contractions (9) was found after 30 sustained maximal contractions, that are much longer and more contractions as during the mMMT testing. The 10- to 15-minute break between test sessions may have been sufficient to allow recovery, so the results do not appear to be affected by fatigue. Recent findings concluding that high scores on fatigue scales do not correlate with inhibitory measures between the somatosensory cortex and the primary motor cortex (10) also support the conclusion that fatigue may not play a role in mMMT testing. Using the isometric 'break' technique in a muscle function test causes high muscle activity around the involved joint to stabilize its position. If spasticity is present in the antagonist or, it may be augmented, which could cause a change in position or movement in adjoining joints, or reduce the measured strength of the agonist, thereby biasing the test. The mMMT was designed to test muscle function selectively and reduce the influence of spasticity. This study found clear hints that the presence of spasticity in the calf muscles did not influence the mMMT outcomes of the testing of the dorsiflexors of the foot, which may be due to the test position and procedures. However, we found that the spasticity measured after the retest had been completed, changed in different ways, which we will now discuss. Increased dorsiflexor muscle tone can alter calf muscle tone (13) if reciprocal inhibition is intact. Multiple maximal ‘break’ tests of the dorsiflexors may increase the dorsiflexor muscle tone. A decrease muscle tone in the calf muscles may be expected (13), if the reciprocal inhibition is intact. A change in the results of spasticity testing after the mMMT tests would be a logical consequence. Indeed, we observed a decrease in MTS (for levels 1 to 3) in 11 participants (or 18 muscle groups) following mMMT testing. As no other procedure could have caused the decrease in spasticity on the testing day, we conclude that the decrease was caused by the testing. A decrease in spasticity in the calf muscles by testing the dorsiflexors also means that the mMMT will not be biased by spasticity in this subgroup and that selective muscle function will be measured. Before the test, MTS-measured spasticity in the calf muscle was low in 12 participants, moderate in 5 and high in 11. After repeated testing, 16 out of 28 participants (or 21 muscle groups) showed an increase in MTS in the calf muscle. Considering that MTS has only 5 levels (0 - 4), the changes in MTS were considerable. Morita et al (38) found that the H-reflex during dorsiflexion was much less reduced in people with long-standing MS presenting spasticity, than in healthy people. Therefore, it cannot be automatically assumed that reciprocal inhibition is intact in MS. The less reciprocal inhibition is present, the less the spasticity should decrease after testing. Among the pwMS in our study individuals with the highest level of spasticity (MTS 4), did not show a decrease in MTS. This can be consistent with significantly reduced reciprocal inhibition. As 4 is the maximum MTS score, it was not possible to measure an increase in spasticity for this subgroup using the MTS. We did not evaluate how these subgroups with and without change in calf muscle spasticity (increased or reduced) might have affected our results. It might be that the presence of lower and higher spasticity after the mMMT testing was a mix that leads to the conclusion that spasticity did not influence the mMMT reliability. Future studies of the mMMT might consider the influence of spasticity (MTS 3 and/or4) on its reliability, assuming that reciprocal inhibition is significantly reduced. For now, we can conclude that we did not find an effect of spasticity on the of mMMT reliability results. Therefore, further studies are needed to evaluate its influence on muscle groups with different levels of spasticity. We observed that the results varied between muscle groups (foot, hip, and elbow flexors). To achieve consistency in testing, a dedicated test should be adopted for each specific muscle function. The test protocols for flexors of the hip, and more so for the elbow, needed to be adjusted. Muscle tests for all groups were newly standardised (61) and tested (16). These efforts showed that the mMMT might provide good inter- and intra-rater reliability, if well trained tester applicated the standardised mMMT. Further studies are needed to assess the reliability of the mMMT, to see if the reliability of the muscle groups used in this study can be confirmed, and to assess the standardisation of other muscle groups. 4.1. Study limitations The testing of only three muscle groups limited the significance of this study in regard of the overall appraisal of the mMMT. Also, the training of the raters in general and the training without persons showing spasticity might have influenced the reliability results. 4.2. Conclusions This study showed that the mMMT might be a reliable measurement tool to test muscle function in pwMS when applied by the same assessor. With its 12 levels, the mMMT could measure small changes in function, making it a reasonable choice for medical professionals treating pwMS. We conclude from our study results that it may be possible to test selective muscle function in the presence of spasticity and MS related fatigue and to reduce the influence of spasticity on muscle testing in pwMS. Abbreviations ANOVA: Analysis of Variance; CI: confidence interval; EDSS: Expanded Disability Status Scale; FSMC: Fatigue Scale for Motor and Cognitive Functions; ICC: Intraclass correlation coefficient; nMMT: modified Manual Muscle Test; MS: multiple sclerosis; MSQPT: Multiple Sclerosis Questionnaire for Physiotherapists; MTS: Modified Tardieu Scale; NRS: numeric rating scale; pwMS: person(s) with MS. Declarations Ethics approval and consent to participate This study was conducted in accordance with the Declaration of Helsinki, the Human Research Act(HRA) and Ordinance on Clinical Trials (ClinO) of Switzerland, and was approved by the Swiss Ethics Board of Northwest and Central Switzerland (project-ID 2018-01103). All participants provided informed consent before participation as was required by the Ethical Committees. Consent for publication Not applicable. Availability of data and material The datasets used and analysed during the current study are available from the corresponding author on reasonable request. Competing interests MDS is an employee of the University Hospital Basel and the CEO of Neurostatus-UHB Ltd. He has received research support from the University Hospital Basel. Funding This study was funded by grants from the Swiss Multiple Sclerosis Society and from the Swiss Specialized Group Physiotherapy in Multiple Sclerosis (FPMS). Authors contributions Nico Arie Van der Maas: Conceptualization, resources, methodology, investigation, data curation, visualization, writing - original draft, review and editing, funding acquisition. Regula Steinlin Egli : Conceptualization, resources, investigation, review and editing, funding acquisition. Deborah R. Vogt : Conceptualization, Methodology, formal analysis, data curation, visualization, review, and editing. Marcus D’Souza : review and editing, funding acquisition. Corresponding Author Nico Arie Van der Maas, Institute for Physiotherapy Research, Bruegg, Switzerland Email: [email protected] Acknowledgements We thank the study participants, the raters, the involved physiotherapists in recruiting participants and for support on the testing days, Marielle Rutquist for data management, the Department of Clinical research of the University Hospital Basel and University of Basel for their support in the preparation of the study, and the University Hospital for Geriatric Medicine and Rehabilitation Felix Platter in Basel for providing the testing site. References Amatya B, Khan F, La Mantia L, Demetrios M, Wade DT. Non pharmacological interventions for spasticity in multiple sclerosis. Cochrane Database Syst Reviews. 2013. 10.1002/14651858.CD009974.pub2 . Asmussen MJ, Mauracher ME, Omu O, Nigg SR, Jarvis SE. Reliability and validity of a novel device for quantifying ankle dorsiflexion force in persons with multiple sclerosis. Mult Scler Relat Disord. 2020. 10.1016/j.msard.2020.101940 . Barin L, Salmen A, Disanto G, Babačic H, Calabrese P, Chan A, Kamm CP, Kesselring J, Kuhle J, Gobbi C, Pot C, Puhan MA, von Wyl V. The disease burden of Multiple Sclerosis from the individual and population perspective: Which symptoms matter most? Mult. Scler Relat Disord. 2018. 10.1016/j.msard.2018.07.013 . Barin L, Kaufman M, Salmen A, Kamm CP, Gobbi C, Kuhle J, Pot C, Chan A, Czaplinski A, Ajdacic-Gross V, Rodgers S, Kesselring J, Puhan MA, von Wyl V. Pattern of care for Multiple Sclerosis in a setting of universal care access: a cross-sectional study. Multiple Scler Relat Disorders. 2018. 10.1016/j.msard.2018.11.033 . Barnes MP, Bhakta BB, Moore P, Richardson D, Salisbury C, Thornton H, Turner-Stokes L, Ward A. The management of adults with spasticity using botulinum toxin: A guide to clinical practice. Surrey, UK: Radius Healthcare, Byfleet; 2001. Barnes MP, Kent RM, Semlyen JK, McMullen KM. Spasticity in multiple sclerosis. Neurorehabil Neural Repair. 2003. 10.1177/0888439002250449 . Baschung Pfister P, de Bruin ED, Sterkele I, Maurer B, de Bie RA, Knols RH. Manual muscle testing and hand-held dynamometry in people with inflammatory myopathy: An intra- and interrater reliability and validity study. PLoS ONE 13, e0194531. 10.1371/journal.pone.0194531 Bohannon RW. Manual muscle testing: does it meet the standards of an adequate screening test? Clin Rehabil. 2005;19(6):662–7. 10.1191/0269215505cr873oa . Brotherton EJ, Sabapathy S, Heshmat S, Kavanagh JJ. Voluntary muscle activation in people with multiple sclerosis is reduced across a wide range of forces following maximal effort-fatiguing contractions. J Neurophysiol. 2023;130:1162–73. 10.1152/jn.00146.2023 . Brotherton EJ, Sabapathy S, Dempsey LM, Kavanagh JJ. Short-latency afferent inhibition is reduced in people with multiple sclerosis during fatiguing muscle contractions. Eur J Neurosci. 2024;59:2087–101. 10.1111/ejn.16253 . Bye E, Glinsky J, Yeomans J, Hungerford A, Patterson H, Chen L, Harvey L. The inter-rater reliability of the 13-point manual muscle test in people with spinal cord injury. Physiother Theory Pract. 2021;37(10):1126–31. 10.1080/09593985.2019.1685033 . Claros-Salinas D, Dittmer N, Neumann M, Sehle A, Spiteri S, Willmes K, Schoenfeld MA, Dettmers C. Induction of cognitive fatigue in MS patients through cognitive and physical load. Neuropsychol Rehabil. 2013;23:182–201. 10.1080/09602011.2012.726925 . Crone C, Hultborn H, Jespersen B, Nielsen J. 1987. Reciprocal Ia inhibition between ankle flexors and extensors in man. J. Physiol. 1987;389:163–185. 10.1113/jphysil.1987.sp016652 Del Blanco JA, Taboada-Iglesias Y. Effects of resistance exercise in patients with spasticity: Systematic review. Apunts Sports Med. 2021;56(212):100356. 10.1016/j.apunsm.2021.100356 . De Lima FX, de Araujo Ribeiro-Alvares JB, de Souza Roberti L, Mocellin MP, Baroni BM. Field Hip Stability Isometric Test (F-HipSIT): Reliability of Assessing the Hip Posterolateral Muscle Strength in Sports Settings. Journal of Sport Rehabilitation. 2024;33(6):478–483. 10.1123/jsr.2023-0146 Dibba l. Bewertung der Reliabilität des modifizierten manuellen Muskelfunktionstest (mMMT) bei Personen mit Multiple Sklerose nach Schulung der Untersucherinnen 2024. https://webthesis.donau-uni.ac.at/thesen/205077.pdf D’Souza M, et al. Electronic Neurostatus-EDSS increases the quality of expanded disability status scale assessments: Experience from two phase 3 clinical trials. Mult Scler. 2020;26(8):993–6. 10.1177/1352458519845108 . Etoom M, Khraiwesh Y, Lena F, Hawamdeh M, Hawamdeh M, Hawamdeh Z, Centonze D, Foti C. Effectiveness of physiotherapy interventions on spasticity in people with multiple sclerosis. Am J Phys Med Rehabil. 2018;97(11):793–807. 10.1097/PHM.0000000000000970 . Eymir M, Unver B, Karatosun V, Reliability. Concurrent Validity, and Minimal Detectable Change of the Hand-Held Dynamometry for the Assessment of Knee Muscle Strength in Patients With Revision Total Knee Arthroplasty. Arch Phys Med Rehabil. 2024;105(1):34–9. 10.1016/j.apmr.2023.05.002 . Florence JM, Pandya S, King WM, Robison JD, Baty J, Miller JP, Schierbecker J, Signore LC. Intrarater reliability of manual muscle test (Medical Research Council scale) grades in Duchenne's muscular dystrophy. Phys Ther. 1992;72:115–22. 10.1093/ptj/72.2.115 . Fortunato R, van der Maas NA, Biland-Thommen U, Kaufmann M, Sieber C, Kamm CP, Zecca C, Gobbi C, Chan A, Calabrese P, Kesselring J, von Wyl V. Physiotherapy use and access-barriers in persons with multiple sclerosis: A cross-sectional analysis. Mult Scler Relat Disord. 2021;48:102710. 10.1016/j.msard.2020.102710 . Frese E, Brown M, Norton BJ. Clinical reliability of manual muscle testing. Middle trapezius and gluteus medius muscles. Phys Ther. 1987;67:1072–6. 10.1093/ptj/67.7.1072 . Gladman D, et al. Fatigue numeric rating scale validity, discrimination and responder definition in patients with psoriatic arthritis. RMD Open. 2020;6:e000928. 10.1136/rmdopen-2019-000928 . Harris-Love M. April. The manual muscle test meeting the challenge of the therapeutic trial 2014. http://moam.info_the_manual_muscle_test_59cf62891723dd8cf17d38d0 (accessed 18 2021). Haugh AB, Pandyan AD, Johnson GR. A systematic review of the Tardieu Scale for the measurement of spasticity. Disabil Rehabil. 2006;28:899–907. 10.1080/09638280500404305 . Hayes KW, Falconer J. 1992. Reliability of hand-held dynamometry and its relationship with manual muscle testing in patients with osteoarthritis in the knee. J. Orthop. Sports Phys. Ther. 1992;16:145–149. 10.2519/jospt.1992.16.3.145 He J. Stretch reflex sensitivity: effects of postural and muscle length changes. IEEE Trans Rehabil Eng. 1998;6:182–9. 10.1109/86.681184 . Hoang PD, Gandevia SC, Herbert RD. Prevalence of joint contractures and muscle weakness in people with multiple sclerosis. Disabil Rehabil. 2014;36:1588–93. 10.3109/09638288.2013.854841 . Hugos CL, Cameron MH. Assessment and measurement of spasticity in MS: State of the evidence. Curr Neurol Neurosci Rep. 2019;19:79. 10.1007/s11910-019-0991-2 . Jørgensen M, Dalgas U, Wens I, Hvid LG. Muscle strength and power in persons with multiple sclerosis - A systematic review and meta-analysis. J Neurol Sci. 2017;376:225–41. http://dx.doi.org/10.1016/j.jns.2017.03.022 . Kakebeeke TH, Lechner H, Baumberger M, Denoth J, Michel D, Knecht H. The importance of posture on the isokinetic assessment of spasticity. Spinal Cord. 2002;40:236–43. http://dx.doi.org/10.1038/sj.sc.3101282 . Kappos L. Neurostatus scoring: Definitions for a standardised, quantified neurological examination and assessment of Kurtzke's Functional Systems and Expanded Disability Status Scale in multiple sclerosis. Version 04/20.2.2011. http://www.neurostatus.net/media/specimen/Definitions_0410-2_s.pdf . Accessed 31 July 2025). Knepler C, Bohannon RW. Subjectivity of Forces Associated with Manual-Muscle Test Grades of 3+, 4-, and 4. Percept Mot Skills. 1998;87(3–suppl):1123–8. 10.2466/pms.1998.87.3f.1123 . Knutsson E, Mårtensson A. Dynamic motor capacity in spastic paresis and its relation to prime mover dysfunction, spastic reflexes and antagonist co-activation. Scand J Rehabil Med. 1980;12:93–106. 10.1016/j.apmr.2006.09.011 . Koo TK, Li MY. A guideline of selecting and reporting intraclass correlation coefficients for reliability research. J Chiropr Med. 2016;15:155–63. 10.1016/j.jcm.2016.02.012 . Krause DA, Schlagel SJ, Stember BM, Zoetewey JE, Hollmann JH. Influence of Lever Arm and Stabilization on Measures of Hip Abduction and Adduction Torque Obtained by Hand-Held Dynamometry. Arch Phys Med Rehabil. 2007;88:37–42. 10.1016/j.apmr.2006.09.011 . Kurzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS) 1983. Neurology;33(11):1444-52. 10.1212/wnl.33.11.1444 Latzel G, Fischbacher Schrobiltgen E. Multiple Sklerose in der Schweiz. In: Die Lebensbedingungen von MS-Betroffenen und die finanziellen Folgen ihrer Krankheit. Schriftenreihe Schweiz Nr. 13 Zürich: Schweizerische MS-Gesellschaft Zürich. 2001. Loy BD, Taylor RL, Fling BW, Horak FB. Relationship between perceived fatigue and performance fatigability in people with multiple sclerosis: A systematic review and meta-analysis. J Psychosom Res. 2017;100:1–7. 10.1016/j.jpsychores.2017.06.017 . Mallucci G, et al. Neurostatus-SMARTCARE clinical trial: Enabling health care professionals to assess EDSS for decentralized trials in multiple sclerosis. Multiple Scler J. 2025;31(4):497–501. 10.1177/13524585241305966 . Mayer NH. Clinicophysiologic concepts of spasticity and motor dysfunction in adults with an upper motoneuron lesion. Muscle Nerve 1997;Suppl. 6:S1–S13. PMID: 9826979. Medical Research Council. Aids to examination of the peripheral nervous system. Memorandum no. 45. London: Her Majesty’s Stationary Office; 1976. Morita H, Crone C, Christenhuis D, Petersen N. Modulation of presynaptic inhibition and disynaptic reciprocal Ia inhibition during voluntary movement in spasticity. Brain. 2001;124(4):826–37. 10.1093/brain/117.5.1161 . Morris SL, Williams G. A historical review of the evolution of the Tardieu Scale. Brain Inj. 2018;32:665–9. 10.1080/02699052.2018.1432890 . Newsome SD, Wang JI, Kang JY, Calabresi PA, Zackowski KM. Quantitative measures detect sensory and motor impairments in multiple sclerosis. J Neurol Sci. 2011;305:103–11. 10.1016/j.jns.2011.03.003 . Ng SS, Hui-Chan CW. Contribution of ankle dorsiflexor strength to walking endurance in people with spastic hemiplegia after stroke. Arch Phys Med Rehabil. 2012;93:1046–51. 10.1016/j.apmr.2011.12.016 . Nielsen J, Sinkjaer T, Toft E, Kagamihara Y. Segmental reflexes and ankle joint stiffness during co-contraction of antagonistic ankle muscles in man. Exp Brain Res. 1994;102:350–8. 10.1007/BF00227521 . Nielsen JB, Christensen MS, Farmer SF, Lorentzen J. Spastic movement disorder: should we forget hyperexcitable stretch reflexes and start talking about inappropriate prediction of sensory consequences of movement? Exp. Brain Res. 2020;238:1627–36. 10.1007/s00221-020-05792-0 . Oesch P et al. Assessments in der Rehabilitation: Band 2. Bewegungsapparat. 3. überarb. u. erw. Auflage. Hogrefe Verlag, Bern. 2017. ISBN 978-3-456-85718-3. Oliveira DG, Oliveira GM, Kirkwood R. Clinimetric Properties of the Applied Kinesiology Manual Muscle Test in Adults With and Without Pain: A Methodological Study. J Chiropr Med. 2022;21(4):260–9. 10.1016/j.jcm.2022.03.003 . Penner IK, Raselli C, Stöcklin M, Opwis K, Kappos L, Calabrese P. The Fatigue Scale for Motor and Cognitive Functions (FSMC): validation of a new instrument to assess multiple sclerosis-related fatigue. Mult Scler. 2009;15:1509–17. 10.1177/1352458509348519 . Philips BA, Lo SK, Mastaglia FL. Muscle force measured using break testing with a hand-held myometer in normal subjects aged 20 to 69 years. Arch Phys Med Rehab. 2000;81(5):653–61. 10.1016/s0003-9993(00)90050-9 . R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. 2018. http://www.R-project.org Schaubert KL, Bohannon RW. Reliability and validity of three strength measures obtained from community-dwelling elderly persons. J Strength Cond Res. 2005;19(3):717–20. 10.1519/r-15954.1 . Schwartz S, Cohen ME, Herbison GJ, Shah A. 1992. Relationship between two measures of upper extremity strength: manual muscle test compared to hand-held myometry. Arch. Phys. Med. Rehabil. 1992:73;1063–1068. PMID: 1444773. Sehle A, Mündermann A, Starrost K, Sailer S, Becher I, Dettmers C, Vieten M. Objective assessment of motor fatigue in multiple sclerosis using kinematic gait analysis: a pilot study. J Neuroeng Rehabil. 2011;8:59. 10.1186/1743-0003-8-59 . Severijns D, Zijdewind I, Dalgas U, Lamers I, Lismont C, Feys P. The assessment of motor fatigability in persons with multiple sclerosis: A systematic review. Neurorehabil Neural Repair. 2017;31:413–31. 10.1177/1545968317690831 . Shindo M, et al. Changes in reciprocal ia inhibition during voluntary contraction in man. Exp Brain Res. 1984;53:400–8. 10.1007/BF00238170 . Spiteri S, Hassa T, Claros-Salinas D, Dettmers C, Schoenfeld MA. Neural correlates of effort-dependent and effort-independent cognitive fatigue components in patients with multiple sclerosis. Mult Scler. 2019;25:256–66. 10.1177/1352458517743090 . Steinlin Egli R. Multiple Sklerose verstehen und behandeln. Berlin Heidelberg New York: Springer-; 2011. 10.1007/978-3-642-17633-3 . Steinlin Egli R. Modifizierte Muskelfunktionsprüfung bei Multipler Sklerose. Berlin: Springer; 2024. 10.1007/978-3-662-68029-2 . Stone CA, Nolan B, Lawlor PG, Kenny RA. Hand-held dynamometry: tester strength is paramount, even in frail populations. J Rehabil Med. 2011;43(9):808–11. 10.2340/16501977-0860 . Terwee C, Bot S, de Boer M, van der Windt D, Knol D, Dekker J, et al. Quality criteria were proposed for measurement properties of health status questionnaires. J Clin Epidemiol. 2007;60(1):34–42. 10.1016/j.jclinepi.2006.03.012 . Thompson AJ, Banwell BL, Barkhof F, Carrol WM, Coetzee T, Comi G, Correale J, Fazekas F, Filippi M, Freedman MS, Fujihara K, Galetta SL, Hartung HP, Kappos J, Lublin FD, Marrie RA, Miller AE, Miller DH, Montalban X, Mowry EM, Sorensen PS, Tintoré M, Traboulsee AL, Trojano M, Uitdehaag BMJ, Vukusic S, Waubant E, Weinshenker BG, Reingold SC, Cohen JA. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018;17:162–73. 10.1016/S1474-4422(17)30470-2 . Van der Maas NA, Biland-Thommen U, Grillo Juszczak T. Die Valididität, Reliabilität und Akzeptanz des Multiple Sclerosis Questionnaire for Physiotherapists (MSQPT). Physioscience. 2010;5:135–42. Van der Maas NA. Patient-reported questionnaires in MS rehabilitation: responsiveness and minimal important difference of the multiple sclerosis questionnaire for physiotherapists (MSQPT). BMC Neurol. 2017;17:50. 10.1186/s12883-017-0834-1 . Wagner JM, Kremer TR, Van Dillen LR, Naismith RT. Plantarflexor weakness negatively impacts walking in persons with multiple sclerosis more than plantarflexor spasticity. Arch Phys Med Rehabil. 2014;95:1358–65. 10.1016/j.apmr.2014.01.030 . Wikholm JB, Bohannon RW. Hand-held Dynamometer Measurements: Tester Strength makes a difference. JOSPT. 1991;13:191–8. 10.2519/jospt.1991.13.4.191 . Wood DE, Burridge JH, van Wijck FM, McFadden C, Hitchcock RA, Pandyan AD, Haugh A, Salazar-Torres JJ, Swain ID. Biomechanical approaches applied to the lower and upper limb for the measurement of spasticity: a systematic review of the literature. Disabil Rehabil. 2005;27:19–32. 10.1080/09638280400014683 . Young CA et al. Fatigue in amyotrophic lateral sclerosis/motor neuron disease: prevalence, influences and trajectories 2025. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. 10.1080/21678421.2025.2533881 Footnotes Abbreviations : CI, confidence interval; FSMC, Fatigue Scale of Motor and Cognition; ICC, intraclass correlation coefficient; mMMT, modified Manual Muscle Test; MS, multiple sclerosis; MTS, Modified Tardieu Scale; NRS, numeric rating scale; pwMS, persons with multiple sclerosis; EDSS, Expanded Disability Status Scale. Additional Declarations Competing interest reported. MDS is an employee of the University Hospital Basel and the CEO of Neurostatus-UHB Ltd. He has received research support from the University Hospital Basel. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7576603","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":537854849,"identity":"f942f797-6a25-4f3f-a48d-ef67ad550538","order_by":0,"name":"Nico Arie Van der Maas","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA70lEQVRIiWNgGAWjYBACNgbGByA6AYghLDYQwdiATwuzAUwLhEVQCwOSFjYJuCA+LXzSzYyPK/7Y5Rncbr9W+bPtTj4f/+EDDD934HGYzGFmw7NtycUGd86U3eZte2bZJpGWwNh7Bo8Wifxjko0NBxI33MhJu83YdtiATYLHgJmxDZ+WZDbJhj8QLYU/QVr4z38gQgsbSEv6MQZekBaGHAb8WkB+aWxLTpx5I4dZmuccyGFpBgd78WiRn93M+LDhj11i3430hx9/lB02kO8//PDBTzxaGBBxwWMAZx7AowFZC/sDvApHwSgYBaNg5AIAlq1SZfsVwrkAAAAASUVORK5CYII=","orcid":"","institution":"Institute for Physiotherapy Research","correspondingAuthor":true,"prefix":"","firstName":"Nico","middleName":"Arie Van der","lastName":"Maas","suffix":""},{"id":537854850,"identity":"cf8b6614-5963-4e03-b6e9-66f41f3aae48","order_by":1,"name":"Regula Steinlin Egli","email":"","orcid":"","institution":"Physiotherapy Langmatten","correspondingAuthor":false,"prefix":"","firstName":"Regula","middleName":"Steinlin","lastName":"Egli","suffix":""},{"id":537854851,"identity":"0def7196-e7fc-43c3-b148-84a419a4d83d","order_by":2,"name":"Deborah R. Vogt","email":"","orcid":"","institution":"University Hospital Basel and University of Basel","correspondingAuthor":false,"prefix":"","firstName":"Deborah","middleName":"R.","lastName":"Vogt","suffix":""},{"id":537854852,"identity":"39d0657f-cb44-4819-8915-06ee69d46f06","order_by":3,"name":"Marcus D’Souza","email":"","orcid":"","institution":"University Hospital Basel","correspondingAuthor":false,"prefix":"","firstName":"Marcus","middleName":"","lastName":"D’Souza","suffix":""}],"badges":[],"createdAt":"2025-09-09 19:08:06","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7576603/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7576603/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":95108459,"identity":"2dbf067a-5770-4f21-9f91-9b8b009e3dd3","added_by":"auto","created_at":"2025-11-04 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1","display":"","copyAsset":false,"role":"figure","size":92890,"visible":true,"origin":"","legend":"\u003cp\u003eAssociation between the overall modified Manual Muscle Test (mMMT) score and fatigue assessed by a numeric rating scale (NRS).\u003c/p\u003e","description":"","filename":"floatimage116.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7576603/v1/52edc187513cb74a0f239354.jpeg"},{"id":95224352,"identity":"ed557f2f-0448-4601-8d78-705c4747530c","added_by":"auto","created_at":"2025-11-05 16:23:39","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":73072,"visible":true,"origin":"","legend":"\u003cp\u003eAssociation between the modified Manual Muscle Test (mMMT) overall score and spasticity score for test and retest.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7576603/v1/3a3864bfab04e2af64c9d5db.jpeg"},{"id":95224757,"identity":"0e84156c-280b-443b-aed4-fea9df5f75c6","added_by":"auto","created_at":"2025-11-05 16:24:15","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":232526,"visible":true,"origin":"","legend":"\u003cp\u003eAssociation between the modified Manual Muscle Test (mMMT) foot score and the corresponding spasticity score for test and retest.\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7576603/v1/63d064bf7edae8e5341919e0.jpeg"},{"id":96916063,"identity":"81610f32-3058-4113-8c8d-2f0776215338","added_by":"auto","created_at":"2025-11-27 14:07:56","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1265428,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7576603/v1/103d34a8-0607-4c4c-8cbb-921d278eeba8.pdf"},{"id":95108454,"identity":"f8681545-92d1-44b9-aaf6-2fa26085bdb7","added_by":"auto","created_at":"2025-11-04 11:25:10","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":16501,"visible":true,"origin":"","legend":"","description":"","filename":"AppendixA.docx","url":"https://assets-eu.researchsquare.com/files/rs-7576603/v1/f3b6fe3bc2cb8427fdd040e7.docx"},{"id":95108458,"identity":"cdd6c644-86db-47f6-894e-5e539872ef34","added_by":"auto","created_at":"2025-11-04 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11:25:11","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":17340,"visible":true,"origin":"","legend":"","description":"","filename":"AppendixD.docx","url":"https://assets-eu.researchsquare.com/files/rs-7576603/v1/15c230ecbee0cbe60c036034.docx"},{"id":95108463,"identity":"a588e38b-c5ee-4662-839c-84e5ba441ccb","added_by":"auto","created_at":"2025-11-04 11:25:10","extension":"docx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":683245,"visible":true,"origin":"","legend":"","description":"","filename":"AppendixE.docx","url":"https://assets-eu.researchsquare.com/files/rs-7576603/v1/679db952ebfc854c465e9793.docx"},{"id":95108472,"identity":"fc444bd7-d85f-4795-9eae-25f51b9bfe8e","added_by":"auto","created_at":"2025-11-04 11:25:10","extension":"pdf","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":83993,"visible":true,"origin":"","legend":"","description":"","filename":"GRRASchecklistforreportingofstudiesofreliabilityandagreement.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7576603/v1/302fef724a6fc8fa6c223392.pdf"}],"financialInterests":"Competing interest reported. MDS is an employee of the University Hospital Basel and the CEO of Neurostatus-UHB Ltd. He has received research support from the University Hospital Basel.","formattedTitle":"The reliability of the modified Manual Muscle Test for persons with MS","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eMany persons with multiple sclerosis (pwMS) undergo physiotherapy due to motor function impairment, a common symptom in multiple sclerosis (MS). Especially in the progressive course of the disease, motor dysfunction is a major contributor to reduced mobility and quality of life (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). Improving motor dysfunction is therefore an important goal of physiotherapy.\u003c/p\u003e\u003cp\u003eOver 60% of pwMS with moderate to severe MS require treatment for spasticity, its associated problems, or both (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e). Spasticity, as well as ataxia, muscle weakness, fatigue, and sensory impairment pose challenges to the treatment and measurement of muscle dysfunction. Muscle function tests can be confounded by these factors, which are not considered by currently available tests including handheld dynamometer and isokinetic dynamometry tests.\u003c/p\u003e\u003cp\u003eAlthough some authors advise against using manual muscle testing to test spastic muscles (\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e) or to diagnose muscle weakness (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e), it is still the most widely used muscle test in neurology, as the classic British Medical Research Council (BMRC) Scale Manual Muscle Test (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e) with 6 grades is part of the EDSS (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e). A manual muscle test has favourable characteristics (quick test, always available and known by most health care professionals) but has the uncertainty of the amount of resistance to be applied when the test is performed with manual resistance.\u003c/p\u003e\u003cp\u003eSpastic movement disorders have recently been defined as disordered sensorimotor control resulting from upper motor neuron lesions and presenting as intermittent or sustained involuntary muscle activation. It is characterised by reduced ability to selectively activate muscles with significant co-activation of antagonist muscles (\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e). In spasticity, the activation of antagonists and synergists of the targeted muscle group may occur during muscle function testing, resulting in a deviation of movement or an increase in muscle tone. Thus, manual muscle tests may not only assess the targeted group of muscles but also interference from antagonists and agonists. Therefore, we may not selectively test the strength of specific muscles and currently available tests might be biased.\u003c/p\u003e\u003cp\u003eWhat can be done to improve muscle testing when a spastic movement disorder is present in pwMS? Posture (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e), sensory input (\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e), and movement speed (\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e) are known to influence spasticity. The modified Manual Muscle Test (mMMT) uses these factors to take spasticity during muscle strength testing into account. It is a novel muscle test for pwMS. (\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e, \u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e). By defining the exact body posture und position of the muscle groups over a specific joint while testing (test position), the acceptable change in the test position, and the sensory input, the influence of spasticity on the test results is minimised (Appendix A). The precise criteria for test conditions and performance describe an acceptable muscle response to manual resistance without discernible spasticity. These criteria are particularly important as the mMMT uses the 'break' test (\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e, \u003cspan citationid=\"CR68\" class=\"CitationRef\"\u003e68\u003c/span\u003e) to achieve maximum performance but increases the risk of enhanced spasticity, which is undesirable. The mMMT is an isometric muscle test with 12 grades, that is easy to perform even in people with a complex neurological condition such as MS.\u003c/p\u003e\u003cp\u003eThe test criteria also describe how long a position should be maintained in grade 2 and above. With its 12 grades, the mMMT can describe smaller differences in muscle function than the most commonly used test in MS, the BMRC manual muscle test, which has six grades.\u003c/p\u003e\u003cp\u003eAny muscle function test used to measure changes due to physiotherapy interventions must reliably assess muscles. Of the muscles typically affected in MS, the tibialis anterior muscle is often the first and worst affected muscle (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). It is significantly weaker in pwMS than in their sex-matched controls (\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e, \u003cspan citationid=\"CR69\" class=\"CitationRef\"\u003e69\u003c/span\u003e). The gastroc-soleus muscle group is most affected by spasticity in pwMS (\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e). These muscles and the dorsal flexors are antagonists that can present weakness, spasticity, loss of reciprocal inhibition, and hyperexcitability (\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e, \u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e). This constellation is a typical example for muscle testing, in which spasticity may influence, and potentially bias, the results if the test position and execution favour an increase in spasticity. Therefore, testing the muscle strength of the dorsal flexors is an effective way to determine whether the mMMT can measure muscle strength in the presence of spasticity without being affected by it. Furthermore, they are exemplary muscle groups that cause walking problems in pwMS (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e, \u003cspan citationid=\"CR67\" class=\"CitationRef\"\u003e67\u003c/span\u003e, \u003cspan citationid=\"CR69\" class=\"CitationRef\"\u003e69\u003c/span\u003e) which underscores the importance of an unbiased and reliable testing. Further, we choose the manual muscle test of the dorsal flexors as the focus, as can be seen in the inclusion criteria of this study. The hip flexors are another muscle group that shows weakness in pwMS and are important for walking (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e). In the presence of spasticity in the tested extremity, this test may produce biased results, as an increase in spasticity during testing may cause the test position to deviate and alter the results. Therefore, we also included hip flexors.\u003c/p\u003e\u003cp\u003eA 'break' test for the upper limb muscles poses a much higher risk of injury to the shoulder joint and muscles if these muscles are weak and unable to stabilize the scapula and shoulder joint. This is particularly true when testing an older population, where problems with the rotator cuff muscles are common. Testing elbow flexion when the upper arm is stabilized against the trunk does not pose such a high risk. As spasticity in the elbow flexors is common in people with pwMS, we have chosen to test the elbow flexors, representing the upper extremities muscle groups. Each participant would be tested multiple times. Interventions with high physical demands, as in this study, may increase the fatigue in pwMS (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e). A significant relationship has been reported between perceived fatigue and fatigability in MS, such that pwMS who reported elevated fatigue are also highly fatigable (\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e) and exhibit greater reductions in muscle strength and voluntary muscle activation (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Therefore, we hypothesised that fatigue could potentially increase with increasing number of tests performed and included fatigue test as a covariate in the statistical model.\u003c/p\u003e\u003cp\u003eTonic dorsiflexion inhibits the activity of the calf muscles in healthy individuals (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Also, Shindo et al (\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e) found that in healthy individuals the increase of reciprocal inhibition of the soleus nerve was positively correlated to the strength of the dorsiflexion. In the case of MS, if the reciprocal inhibition is still intact, weak dorsiflexors causes less inhibition. An increase in muscle tone resp. spasticity due to multiple testing and the use of the 'break' test principle could also be expected. Performing a maximal test in a region of the body with a higher level of spasticity could cause greater movement deviation during testing and result in a lower test score in the later tests. This would alter the inter- and intrarater reliability of the test. We considered this to be a major problem in the trial, so we assessed the effect of multiple testing on spasticity and took steps to address this issue. To reduce the risk of testing induced spasticity, pwMS were given a break of at least 10 minutes between tests to allow them to rest. In addition, an hour break was planned between the test and retest series.\u003c/p\u003e\u003cp\u003eThe aim of this study was to evaluate the inter- and intrarater reliability of the mMMT for dorsal flexion of the foot and hip and elbow flexion in pwMS. Furthermore, we evaluated the influence of fatigue and spasticity on the reliability of the test results.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003ch2\u003e2.1. \u0026nbsp; \u0026nbsp; \u0026nbsp; Study design and ethical considerations\u003c/h2\u003e\n\u003cp\u003eThis single-centre, prospective, cross-sectional study was carried out as a test-retest within 4 h at the University Hospital for Geriatric Medicine and Rehabilitation Felix Platter, Basel.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the Declaration of Helsinki, the Human Research Act of Switzerland (HRA) and Ordinance on Clinical Trials (ClinO), and was approved by the Swiss Ethics Board of Northwest and Central Switzerland (project-ID 2018-01103). All participants provided informed consent before participation.\u003c/p\u003e\n\u003cp\u003eThe primary objective was to show that the mMMT has a high interrater reliability, defined as an intra-class correlation coefficient (ICC) of at least 0.7 (prespecified ICC margin) (33, 58). The null hypothesis was that the lower limit of the 95% confidence interval (CI) of the ICC is smaller or equal to the ICC margin.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll participants were assessed twice (at the test and retest stages) by six raters, three experienced neurologists and three MS-specialised physiotherapists (see Appendix B).\u003c/p\u003e\n\u003cp\u003eThree raters used the mMMT and the other three used the BMRC manual muscle test of the Neurostatus EDSS (17, 32, 40) (these results will be reported elsewhere). Raters assessed the three muscle groups (dorsal flexion of the foot, and hip and elbow flexion) on the left and right side. The raters were allocated to study participants in random order and were blinded to the ratings of the other raters. pwMS were given a break of at least 10 minutes between tests. Between test and retest sessions, the participants were given an hour break to relax.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe considered increasing spasticity to be the most important confounder. Assuming that participants with higher levels of spasticity in the tested limb would have a higher risk of increasing spasticity over time, we repeated the primary analyses for subgroups of patients with high and low spasticity to assess the influence of increasing spasticity on interrater reliability. The Modified Tardieu Scale (MTS) (23, 27, 39) was used\u0026nbsp;to determine the degree of spasticity and to define high and low spasticity (MTS score 3 or 4 and 0 or 1, respectively).\u003c/p\u003e\n\u003cp\u003eTo account for confounding by increasing fatigue, the primary analysis was repeated with the order of the ratings included as covariate in the statistical model. This approximation was used since patients\u0026rsquo; self-assessment of fatigue via NRS was only done at baseline (before performing the first muscle test) and at the end of the examinations (after performing the last muscle test). The secondary objective was to examine the intrarater reliability of the mMMT. using a test \u0026ndash; retest procedure.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe also examined the association of the mMMT with self-reported fatigue and spasticity, and test time for the test-retest results as covariates in the statistical model.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo assess the relation between the test-retest results of the mMMT and fatigue and spasticity resp., we used a 11-point fatigue Numerical Rating Scale (NRS) (23, 70) and\u0026nbsp;MTS scores resp. that we administered before muscle testing started and after the last mMMT retest. These associations were\u003c/p\u003e\n\u003cp\u003eexamined exploratively by plotting test and retest ratings against the fatigue NRS respectively\u003c/p\u003e\n\u003cp\u003emodified Tardieu scale.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe evaluated the influence of the test time, i.e., the number of hours since\u0026nbsp;the\u0026nbsp;start of\u0026nbsp;the\u0026nbsp;test day, on fatigue and spasticity. We expected that this would be useful as a surrogate measure of participants fatigue and spasticity and, hence, could be related\u0026nbsp;to\u0026nbsp;the mMMT scores.\u0026nbsp;The relations between the mMMT and testing time was investigated exploratively.\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Ethics Board of Northwest and Central Switzerland (ID: 2018-01103) and pre-registered at ClinicalTrials.gov (ID: NCT03603691). All participants provided a written informed consent. Two training sessions were held to familiarise the experienced accessors with the use of the mMMT.\u003c/p\u003e\n\u003ch2\u003e2.2. \u0026nbsp; \u0026nbsp; \u0026nbsp; Study population\u003c/h2\u003e\n\u003cp\u003eParticipants were diagnosed with MS according to the McDonald criteria (64), had an EDSS of between 0 and 6.5, and were older than 18 years. We enrolled persons with mMMT scores 2+ to 4+ or Neurostatus manual muscle scores between 2 and 5 for the dorsal flexion muscles tests of the foot. As previously discussed, the gastroc-soleus muscle group is most affected by spasticity in pwMS (46) and the tibialis anterior muscle is often the first and most affected muscle in pwMS (2). By defining these muscle scores as inclusion criteria, we ensured, that muscle weakness and/or spasticity would be present in the study population, and that using the mMMT testing method that minimises the influence of spasticity would make sense. Exclusion criteria were an acute MS episode within three months prior to testing, severe cognitive changes or distinct fatigue that made it impossible to perform the experiment for four hours, and current back, neck, or elbow pain. Participants were recruited from MS specialised physiotherapy institutions and hospitals (Appendix B).\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003e2.3.\u0026nbsp;Other outcome measures\u003c/h2\u003e\n\u003cp\u003eWe used the Fatigue Scale for Motor and Cognitive Functions (FSMC) questionnaire (51) to quantify MS-related fatigue and decide whether the pwMS could be included in the study, i.e. the pwMS did not have distinct fatigue, defined as an FSMC motor score =\u0026gt; 27. The pwMS completed the FSMC questionnaire prior to inclusion in the study.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003e2.4. \u0026nbsp; \u0026nbsp; \u0026nbsp; Statistical analysis\u003c/h2\u003e\n\u003cp\u003eSample size was estimated using a resampling approach (Appendix C). Allowing for a drop-out rate of 10%, 28 pwMS were required to have at least 80% power to detect a clinically relevant intraclass correlation coefficient (ICC) of \u0026gt; 0.70 (35) for the mMMT results, based on a 95% confidence interval (CI).\u003c/p\u003e\n\u003cp\u003eAll analyses were preplanned in a statistical report and analysis plan and conducted using the R statistical software packages (53), based on available data from all 28 included pwMS. Reported confidence intervals were not adjusted for multiple testing.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe mMMT interrater reliability was assessed by the ICC based on a one-way random effects ANOVA model, considering an absolute agreement (R package \u0026lsquo;\u0026rsquo;psych\u0026rsquo;\u0026rsquo;). The ICC was calculated for each mMMT item separately, for each mMMT muscle group separately, and for the overall mMMT score. Analyses were adjusted for fatigue by including the rating order as covariate. The analysis was repeated separately for subgroups of participants with high (MTS baseline score \u0026ge;\u003cem\u003e\u0026nbsp;\u003c/em\u003e3) and low (MTS baseline score \u0026le;\u003cem\u003e\u0026nbsp;\u003c/em\u003e1) spasticity in the foot (high spasticity scores were not observed in other muscle groups). For the overall mMMT score, foot spasticity was used as a reference.\u003c/p\u003e\n\u003cp\u003eThe mMMT intrarater reliability was first estimated for each rater separately, using two-way random-effects ANOVA models, considering absolute agreement. Then, a pooled estimate was derived by combining all ratings and including raters as a covariate.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAssociations of the mMMT score with fatigue and spasticity were examined exploratively by plotting test and retest ratings against fatigue NRS and MTS scores, respectively. We further examined the overall association with linear mixed-effects model for each test separately. The models included the mMMT score as the dependent variable, the corresponding fatigue NRS rating or MTS groups (continuous variable) and test type (test or retest) as independent variables (fixed effects), and participant and rater as random effects (random intercepts). We also investigated the interaction of NRS and MTS scores with the test type. The relationship of the mMMT score with testing time was investigated exploratively using line plots.\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003eThe study participants were all recruited by physiotherapists and were receiving physiotherapy. They were older, had been affected by MS longer and had higher EDSS scores than the population of pwMS receiving physiotherapy in the Swiss MS Registry (Table 1). The study participants were also older and had been affected longer than the pwMS in physiotherapy treatment of the plausibly representative Swiss March study (38) and of the representative studies of the Multiple Sclerosis Questionnaire for Physiotherapists (MSQPT) (65, 66). Therefore, the mMMT study is not representative of the Swiss pwMS population receiving physiotherapy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1\u0026nbsp;\u003c/strong\u003eDemographic data.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"448\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 197px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003emMMT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003eSwiss MS Registry*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 197px;\"\u003e\n \u003cp\u003eFemale (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003e68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e73\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 197px;\"\u003e\n \u003cp\u003eAge (mean, years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e52\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 197px;\"\u003e\n \u003cp\u003e\u003cem\u003en\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e693\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 197px;\"\u003e\n \u003cp\u003eYears of illness (mean)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 197px;\"\u003e\n \u003cp\u003eEDSS 0\u0026ndash;3.5 (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003e25.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e45.3**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 197px;\"\u003e\n \u003cp\u003eEDSS 4\u0026ndash;6.5 (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003e75.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e25.1**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 197px;\"\u003e\n \u003cp\u003eEDSS 7\u0026ndash;9.5 (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003e0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e13.1**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*Persons with MS regularly using physiotherapy (20).\u003c/p\u003e\n\u003cp\u003e** An EDSS proxy, estimated based on self-reported walking distances.\u003c/p\u003e\n\u003cp\u003eAbbreviations: EDSS, Expanded Disability Status Scale; mMMT, modified Manual Muscle Test; MS, multiple sclerosis.\u003c/p\u003e\n\u003cp\u003eParticipants were tested with the FSMC prior to enrolment to determine their motor fatigue, and 21 out of 28 pwMS had severe motor fatigue. One pwMS withdrew after five manual muscle tests due to hip pain, one FSMC was missing after testing and 0.51% of MTS values were missing.\u003c/p\u003e\n\u003cp\u003eBefore testing, the MTS test for the calf muscles (both sides) showed 16 tests without spasticity (MTS 0), 6 tests with discrete spasticity (MTS 1), 16 tests with a moderate spasticity (MTS 2) and 17 tests with a high level of spasticity (MTS 3 and 4). The other muscle groups showed discrete to moderate spasticity in 26 tests and no tests with a high level of spasticity. 1 MTS result was missing.\u003c/p\u003e\n\u003cp\u003eAfter the mMMT retests, the MTS test for the calf muscles showed fewer tests without (10), more tests with discrete (15) or moderate (18) spasticity, and fewer tests with high levels of spasticity (13).\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003e3.1. \u0026nbsp; \u0026nbsp; \u0026nbsp; Interrater reliability of the mMMT\u003c/h2\u003e\n\u003cp\u003eThe targeted prespecified ICC margin of 0.7 was not reached for any of the assessed levels (Table 2). The overall ICC was rather poor. The highest ICC values were observed on the left body side.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThere was high rating variability for most pwMS. Only a few pwMS received the same rating from all three assessors. It also appeared that certain raters tended to give generally low or high ratings.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e\u0026nbsp; ICCs and 95% confidence intervals for interrater reliability of the overall mMMT score, for each muscle group, and for each body side per muscle group.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"274\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003eLevel\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003eICC [95% CI]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003eOverall\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e0.30 [0.07, 0.54]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003eFoot\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e0.39 [0.16, 0.62]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003eFoot left\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e0.64 [0.45, 0.80]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003eFoot right\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e0.48 [0.26, 0.69]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003eHip\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e0.36 [0.13, 0.59]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003eHip left\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e0.64 [0.44, 0.80]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003eHip right\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e0.29 [0.06, 0.54]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003eElbow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e0.32 [0.09, 0.56]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003eElbow left\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e0.63 [0.43, 0.79]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003eElbow right\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e0.00 [-0.18, 0.25]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: CI, confidence interval; ICC, intraclass correlation coefficient.\u003c/p\u003e\n\u003cp\u003eAdjusting for test order did not change the ICC estimates of interrater reliability (Table 3). This suggests that there was no general association between ratings and potential fatigue.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u0026nbsp;\u003c/strong\u003eICCs and 95% confidence intervals for interrater reliability adjusted for fatigue by test order.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"247\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003eLevel\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003eICC [95% CI]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003eOverall\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 108px;\"\u003e\n \u003cp\u003e0.29 [0.06, 0.53]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003eFoot\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 108px;\"\u003e\n \u003cp\u003e0.38 [0.10, 0.61]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003eFoot left\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 108px;\"\u003e\n \u003cp\u003e0.64 [0.41, 0.79]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003eFoot right\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 108px;\"\u003e\n \u003cp\u003e0.48 [0.21, 0.68]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003eHip\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 108px;\"\u003e\n \u003cp\u003e0.35 [0.11, 0.57]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003eHip left\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 108px;\"\u003e\n \u003cp\u003e0.63 [0.43, 0.78]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003eHip right\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 108px;\"\u003e\n \u003cp\u003e0.29 [0.00, 0.53]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003eElbow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 108px;\"\u003e\n \u003cp\u003e0.32 [0.03, 0.56]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003eElbow left\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 108px;\"\u003e\n \u003cp\u003e0.62 [0.40, 0.78]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003eElbow right\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 108px;\"\u003e\n \u003cp\u003e0.00 [0.00, 0.24]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: CI, confidence interval; ICC, intraclass correlation coefficient.\u003c/p\u003e\n\u003cp\u003eHigh levels of spasticity were only observed in the foot (Table 4). Therefore, the spasticity subgroup analysis was only performed for the mMMTs foot (each body side separately and pooled) and for the mMMT overall. For the mMMT overall the spasticity subgroups of the foot pooled were used.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe found no evidence that interrater reliability differed between pwMS with high and low spasticity scores in the foot (Table 4). The pooled data for both feet show that the mean ICC for pwMS with low spasticity scores is lower than for pwMS with high spasticity scores; however, the 95% confidence intervals largely overlap.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4\u0026nbsp;\u003c/strong\u003eICC and 95% confidence intervals for subgroups with high and low spasticity scores.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"433\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003eLevel\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003e\u0026nbsp;low spasticity score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 181px;\"\u003e\n \u003cp\u003ehigh spasticity score\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003eOverall\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003e0.33 [-0.01, 0.70]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 181px;\"\u003e\n \u003cp\u003e0.29 [-0.06, 0.69]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003eFoot\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003e0.22 [-0.11, 0.62]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 181px;\"\u003e\n \u003cp\u003e0.50 [0.13, 0.80]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003eFoot left\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003e0.59 [0.23, 0.86]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 181px;\"\u003e\n \u003cp\u003e0.57 [0.18, 0.86]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003eFoot right\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003e\u0026nbsp;0.56 [0.19, 0.85]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 181px;\"\u003e\n \u003cp\u003e0.51 [0.13, 0.83]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: CI, confidence interval; ICC, intraclass correlation coefficient.\u003c/p\u003e\n\u003ch2\u003e3.2. \u0026nbsp; \u0026nbsp; \u0026nbsp; Intrarater reliability of the mMMT\u003c/h2\u003e\n\u003cp\u003eThe mMMT intrarater reliability was good. However, there was a considerable variability between raters (Table 5). Looking at different muscle groups, the intrarater reliability was highest for the foot, followed by the hip and elbow. The pooled overall value was 0.77, which exceeded the 0.75 limit for good reliability (33 ,58).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5\u0026nbsp;\u003c/strong\u003eIntrarater reliability of the modified Manual Muscle Test (mMMT).\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 117px;\"\u003e\n \u003cp\u003eLevel\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003eRater 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003eRater 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003eRater 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003eRater 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eRater 5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003eRater 6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003ePooled\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 117px;\"\u003e\n \u003cp\u003eOverall\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e0.61 [0.12, 0.86]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e0.68 [0.10, 0.90]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003e0.84 [0.58, 0.94]\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e0.90 [0.72, 0.96]\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e0.97 [0.88, 0.99]\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e0.97 [0.92, 0.99]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e0.77 [0.65, 0.86]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 117px;\"\u003e\n \u003cp\u003eFoot\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e0.64 [0.20, 0.87]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e0.75 [0.33, 0.92]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003e0.74 [0.38, 0.91]\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e0.85 [0.61, 0.95]\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e0.98 [0.90, 0.99]\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e0.97 [0.91, 0.99]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e0.75 [0.62, 0.84]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 117px;\"\u003e\n \u003cp\u003eFoot left\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e0.73 [0.36, 0.90]\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e0.70 [0.27, 0.89]\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003e0.84 [0.58, 0.94]\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e0.90 [0.73, 0.97]\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e0.95 [0.76, 0.99]\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e0.99 [0.96, 1.00]\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e0.80 [0.67, 0.88]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 117px;\"\u003e\n \u003cp\u003eFoot right\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e0.40 [-0.11, 0.75]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e0.87 [0.64, 0.95]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003e0.77 [0.44, 0.92]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e0.91 [0.75, 0.97]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e0.99 [0.97, 1.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e0.98 [0.93, 0.99]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e0.76 [0.63, 0.85]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 117px;\"\u003e\n \u003cp\u003eHip\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e0.43 [-0.05, 0.77]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e0.74 [0.28, 0.91]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003e0.69 [0.30, 0.89]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e0.72 [0.35, 0.90]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e0.92 [0.73, 0.98]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e0.87 [0.66, 0.95]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e0.70 [0.53, 0.81]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 117px;\"\u003e\n \u003cp\u003eHip left\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e0.33 [-0.16, 0.71]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e0.72 [0.34, 0.90]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003e0.84 [0.59, 0.95]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e0.89 [0.71, 0.96]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e0.96 [0.86, 0.99]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e0.89 [0.73, 0.96]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e0.76 [0.61, 0.86]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 117px;\"\u003e\n \u003cp\u003eHip right\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e0.58 [0.11, 0.84]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e\u0026nbsp;0.68 [0.21, 0.89]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003e0.58 [0.10, 0.84]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e0.68 [0.27, 0.88]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e0.90 [0.69, 0.97]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e0.75 [0.42, 0.90]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e0.59 [0.42, 0.74]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 117px;\"\u003e\n \u003cp\u003eElbow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e0.55 [0.01, 0.84]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e0.65 [0.23, 0.87]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003e0.93 [0.79, 0.98]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e0.88 [0.68, 0.96]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e1.00 [1.00, 1.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e0.96 [0.89, 0.98]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e0.66 [0.47, 0.78]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 117px;\"\u003e\n \u003cp\u003eElbow left\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e0.76 [0.40, 0.92]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e0.84 [0.59, 0.95]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003e0.92 [0.78, 0.97]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e1.00 [1.00, 1.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e1.00 [1.00, 1.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e0.98 [0.94, 0.99]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e0.81 [0.69, 0.89]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 117px;\"\u003e\n \u003cp\u003eElbow right\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e0.42 [-0.10, 0.77]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e0.06 [-0.40, 0.54]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003e0.54 [0.08, 0.82]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e0.33 [-0.21, 0.72]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e1.00 [1.00, 1.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e0.77 [0.47, 0.91]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e0.22 [0.06, 0.39]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTest-retest intraclass correlation coefficients with 95% confidence intervals are reported for each rater separately and pooled for all raters.\u003c/p\u003e\n\u003ch2\u003e3.3. \u0026nbsp; \u0026nbsp; \u0026nbsp; Associations between the mMMT score and fatigue\u003c/h2\u003e\n\u003cp\u003eThe relationships of the overall mMMT results with fatigue (NRS) are shown in figure 1. The relationships between the overall mMMT score and the overall spasticity (MTS) scores, and between the mMMT foot score and the spasticity foot score for test and retest are shown in figure 2 resp. figure 3.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNone of these figures indicate an association of the mMMT with fatigue or spasticity.\u003c/p\u003e\n\u003cp\u003eAlso, when investigating these relationships further with linear mixed-effects models, including random intercepts for rater and patient, we found no statistical evidence for an association. (Appendix D).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn conclusion, our data do not provide evidence that the mMMT results are influenced by fatigue or spasticity.\u003c/p\u003e\n\u003ch2\u003e3.4. \u0026nbsp; \u0026nbsp; \u0026nbsp; Associations between the mMMT score and testing time\u003c/h2\u003e\n\u003cp\u003eWe have also evaluated the influence of the test time, i.e., the number of hours since the start of the test day, on fatigue and spasticity. We expected that this would be useful as a surrogate measure of participants fatigue and spasticity and, hence, could be related to the mMMT scores. However, based on a visual inspection of the plots, no overall relationship was apparent (Appendix E).\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThe main findings of this study are that the mMMT can be a reliable outcome measure for muscle function if performed by the same medical professional treating the pwMS, that fatigue does not affect test reliability, and that the spasticity degree does not affect the mMMT score. With these characteristics, the mMMT can be a valuable measurement for evaluating the effects of exercises to enhance muscle function in the presence of spasticity.\u003c/p\u003e\n\u003cp\u003eThe inclusion criteria resulted in a study population that was older, had a higher mean number of years of disease, and predominantly had an EDSS between 4 and 6 compared to the Swiss MS registry population using physiotherapy (21). Considering that only 44% of the pwMS in Switzerland receiving physiotherapy (4), the population of this study was not representative of the Swiss MS population nor of the Swiss MS population using physiotherapy. This can be explained by the inclusion criteria of the manual muscle test score between 2 and 5 for the dorsal flexors of the foot. This criterion was designed to ensure that the population has weakness and its associated spasticity in the lower limb, so that testing with the mMMT would be meaningful, as the mMMT takes spasticity into account when testing. The results show that this criterion was sufficient to ensure spasticity in the calf muscles as only 10 of 56 tests did not show spasticity after the retests. Spasticity is directly correlated with disease progression (1): pwMS in the early stages of their disease rarely have spasticity, whereas for the more progressed pwMS spasticity is more likely. Therefore, it was to be expected that our population would be more severely affected by MS than the general MS population in Switzerland.\u003c/p\u003e\n\u003cp\u003eDoes that influence our conclusions or the generalisation of our results? One could argue that a manual muscle test that takes spasticity into account would also work for muscles without spasticity. The mMMT for individuals without spasticity is a more complex test than a regular muscle test but given the same administration, the mMMT should produce similar results as another manual muscle test. If so, the mMMT could be used for pwMS with or without spasticity, but with an EDSS =\u0026lt;6.5, the highest EDSS score in our population. We conclude that the unrepresentative nature of the study population does not limit the conclusions of this study or the generalisability of its results.\u003c/p\u003e\n\u003cp\u003eWe found that mMMT interrater reliability was poor and that this study does not support its use in comparative studies. The mMMT has 4 grades against gravity, that are executed with manual resistance that needs to be judged to be a small to maximum resistance. A large number of grades against gravity (24) and subjectivity of judgement renders it difficult to achieve good reliability (8, 22). These factors surely might play a role, at least in the interrater reliability as the judgement of what is slight, moderate, high or maximum resistance might be different also between experienced raters, as in our study, in which certain raters tended to give generally low or high ratings, which influenced the interrater reliability. Several authors (7, 22, 24) stated that individual tester characteristics influence the test results for manual muscle tests, as also is the case for muscle tests using handheld dynamometry (36, 54, 62). Tester strength is one factor that can have an impact (63), even if participants are of low strength, as reported by Stone et al (62), who found that reliability can be compromised by inadequate muscle strength of the rater. Other individual factors that influence the test results may include a slightly different point and line of application and type of instruction, the tone of the tester\u0026apos;s voice and the interaction between tester and patient (22), all of which can be standardised to some extent in tester training. The highly experienced testers received training on the application in two sessions, which may have been insufficient. Also, training the raters in the absence of people with spasticity may have played a role. In a follow-up study with adjusted standardizing of the mMMT (16), more intensive training of the 6 raters with persons presenting spasticity significantly improved interrater reliability (ICC 0.60-0.87), highlighting the importance of rater training in pwMS to achieve homogeneous mMMT reliability results.\u003c/p\u003e\n\u003cp\u003eAnother factor that could have influenced the test results, is the number of raters used to calculate inter-rater reliability. Often 2 raters are used to assess inter-rater reliability (11, 15, 19, 50). Knepler and Bohannon (33) found that 10 raters varied in the forces they applied for each MMT grade over 3. The variability of test results between raters tends to increase when more than 2 raters are used and, of course, when more grades above 3 are available, as in this study. This is also an uncomfortable tendency for our study, which again emphasises the importance of training raters in a day-to-day environment to ensure reliable test results. Using multiple raters in a reliability study can lead to more ecologically valid results and is recommended for reliability studies of manual muscle tests.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe intrarater reliability of the mMMT (ICC\u0026gt;0.7) can be considered good according to Koo and Li (35) and Terwee at al. (63). The results of the three muscle function tests indicated that the intrarater reliability strongly depended on the muscle group tested, in line with the results of other studies (7,20, 55). The right elbow flexion showed unexpectedly poor reliability in our study, which negatively affected the overall reliability rating. In contrast, the left elbow tests showed good intra-rater reliability. Most reliability results favoured more or less the left side, indicating a difference in test reliability between the right and left sides of the body. This difference can only be explained by the tester\u0026rsquo;s different position on each side and the way in which the test was executed. These findings confirm the need to develop specific, standardised tests for each muscle group, with defined positions and executions for each side, as well as intensive training to achieve higher reliability.\u003c/p\u003e\n\u003cp\u003eWe did not evaluate the influence of fatigue on the test results individually. However, the data of the elbow test showed no indication that fatigue could explain this unexpectedly poor reliability.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eManual muscle tests are an important tool to evaluate the results of exercise on the muscle function in the daily treatment of persons with MS. The mMMT intrarater reliability of this study indicates that it is a useful tool for testing muscle function, if executed by the same person, which is mostly the treating health care professional. An improvement of the intrarater reliability should be possible when the above-mentioned factors will be considered.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSteinlin Egli (61) further standardised the mMMT per muscle group. A follow-up study with selected further standardised muscle groups (16) also showed a slight to substantial improvement in intra-rater reliability compared to this study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn the preparation of this study, we stipulated that executing multiple muscle tests in a population with motor fatigue could influence the reliability results and included pre- and post-testing of fatigue with the FSMC and numerical rating scale for fatigue. We found that our study cohort showed high levels of motor fatigue on the FSMC (score \u0026gt;=32 in 21 pwMS) and 18 pwMS with a worsening of the numerical rating scale for fatigue between 2 (n=4) and 6 (n=4) levels, a worsening we expected. \u0026nbsp;Loy et al (36) reported a significant relationship between perceived fatigue and fatigability in pwMS, such that those reporting higher levels of fatigue are highly fatigable. Cognitive and motor fatigue may increase in pwMS during interventions with high physical demands (12, 56), as was the case in our study. Furthermore, motor fatigability might be closely related to motor symptoms in MS (57), leading to the assumption that increased fatigue might alter motor symptoms. Spiteri et al. (59) investigated effort-dependent and -independent components of fatigue in pwMS and concluded that effort might cause a reduction in activity in executive networks of specific brain regions. With this theoretical background, an influence of fatigue might be expected in the later tests. If fatigue played a role in our results, we did not find indications that an enhanced fatigue influenced any of the reliability measures even after performing multiple tests per pwMS. Adjusting the mMMT results for fatigue by test order did not change the ICC estimates.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSeverijns et al (57) found that a sustained maximal voluntary contraction of 15-180 s induced greater fatigability in pwMS than in healthy controls. The mMMT uses isometric contractions of 1-3 s. These contractions may have been too short to increase motor fatigue during the test. The reported reduced ability to activate muscles following maximal effort-fatiguing contractions (9) was found after 30 sustained maximal contractions, that are much longer and more contractions as during the mMMT testing. The 10- to 15-minute break between test sessions may have been sufficient to allow recovery, so the results do not appear to be affected by fatigue. Recent findings concluding that high scores on fatigue scales do not correlate with inhibitory measures between the somatosensory cortex and the primary motor cortex (10) also support the conclusion that fatigue may not play a role in mMMT testing.\u003c/p\u003e\n\u003cp\u003eUsing the isometric \u0026apos;break\u0026apos; technique in a muscle function test causes high muscle activity around the involved joint to stabilize its position. If spasticity is present in the antagonist or, it may be augmented, which could cause a change in position or movement in adjoining joints, or reduce the measured strength of the agonist, thereby biasing the test.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe mMMT was designed to test muscle function selectively and reduce the influence of spasticity. This study found clear hints that the presence of spasticity in the calf muscles did not influence the mMMT outcomes of the testing of the dorsiflexors of the foot, which may be due to the test position and procedures. However, we found that the spasticity measured after the retest had been completed, changed in different ways, which we will now discuss.\u003c/p\u003e\n\u003cp\u003eIncreased dorsiflexor muscle tone can alter calf muscle tone (13) if reciprocal inhibition is intact. Multiple maximal \u0026lsquo;break\u0026rsquo; tests of the dorsiflexors may increase the dorsiflexor muscle tone. A decrease muscle tone in the calf muscles may be expected (13), if the reciprocal inhibition is intact. A change in the results of spasticity testing after the mMMT tests would be a logical consequence. Indeed, we observed a decrease in MTS (for levels 1 to 3) in 11 participants (or 18 muscle groups) following mMMT testing. As no other procedure could have caused the decrease in spasticity on the testing day, we conclude that the decrease was caused by the testing. A decrease in spasticity in the calf muscles by testing the dorsiflexors also means that the mMMT will not be biased by spasticity in this subgroup and that selective muscle function will be measured.\u003c/p\u003e\n\u003cp\u003eBefore the test, MTS-measured spasticity in the calf muscle was low in 12 participants, moderate in 5 and high in 11. After repeated testing, 16 out of 28 participants (or 21 muscle groups) showed an increase in MTS in the calf muscle. Considering that MTS has only 5 levels (0 - 4), the changes in MTS were considerable. Morita et al (38) found that the H-reflex during dorsiflexion was much less reduced in people with long-standing MS presenting spasticity, than in healthy people. Therefore, it cannot be automatically assumed that reciprocal inhibition is intact in MS. The less reciprocal inhibition is present, the less the spasticity should decrease after testing. Among the pwMS in our study individuals with the highest level of spasticity (MTS 4), did not show a decrease in MTS. This can be consistent with significantly reduced reciprocal inhibition. As 4 is the maximum MTS score, it was not possible to measure an increase in spasticity for this subgroup using the MTS.\u003c/p\u003e\n\u003cp\u003eWe did not evaluate how these subgroups with and without change in calf muscle spasticity (increased or reduced) might have affected our results. It might be that the presence of lower and higher spasticity after the mMMT testing was a mix that leads to the conclusion that spasticity did not influence the mMMT reliability. Future studies of the mMMT might consider the influence of spasticity (MTS 3 and/or4) on its reliability, assuming that reciprocal inhibition is significantly reduced. For now, we can conclude that we did not find an effect of spasticity on the of mMMT reliability results.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTherefore, further studies are needed to evaluate its influence on muscle groups with different levels of spasticity. We observed that the results varied between muscle groups (foot, hip, and elbow flexors). To achieve consistency in testing, a dedicated test should be adopted for each specific muscle function. The test protocols for flexors of the hip, and more so for the elbow, needed to be adjusted. Muscle tests for all groups were newly standardised (61) and tested (16). These efforts showed that the mMMT might provide good inter- and intra-rater reliability, if well trained tester applicated the standardised mMMT.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFurther studies are needed to assess the reliability of the mMMT, to see if the reliability of the muscle groups used in this study can be confirmed, and to assess the standardisation of other muscle groups.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003e4.1. Study limitations\u003c/h2\u003e\n\u003cp\u003eThe testing of only three muscle groups limited the significance of this study in regard of the overall appraisal of the mMMT. Also, the training of the raters in general and the training without persons showing spasticity might have influenced the reliability results. \u003c/p\u003e\n\u003ch2\u003e4.2.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Conclusions\u003c/h2\u003e\n\u003cp\u003eThis study showed that the mMMT might be a reliable measurement tool to test muscle function in pwMS when applied by the same assessor. With its 12 levels, the mMMT could measure small changes in function, making it a reasonable choice for medical professionals treating pwMS. We conclude from our study results that it may be possible to test selective muscle function in the presence of spasticity and MS related fatigue and to reduce the influence of spasticity on muscle testing in pwMS.\u0026nbsp;\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eANOVA: Analysis of Variance; CI: confidence interval; EDSS: Expanded Disability Status Scale; FSMC: Fatigue Scale for Motor and Cognitive Functions; ICC: Intraclass correlation coefficient; nMMT: modified Manual Muscle Test; MS: multiple sclerosis; MSQPT: Multiple Sclerosis Questionnaire for Physiotherapists; MTS: Modified Tardieu Scale; NRS: numeric rating scale; pwMS: person(s) with MS.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the Declaration of Helsinki, the Human Research Act(HRA) and Ordinance on Clinical Trials (ClinO) of Switzerland, and was approved by the Swiss Ethics Board of Northwest and Central Switzerland (project-ID 2018-01103).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll participants provided informed consent before participation as was required by the Ethical Committees.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMDS is an employee of the University Hospital Basel and the CEO of Neurostatus-UHB Ltd. He has received research support from the University Hospital Basel.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was funded by grants from the Swiss Multiple Sclerosis Society and from the Swiss Specialized Group Physiotherapy in Multiple Sclerosis (FPMS).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNico Arie Van der Maas:\u0026nbsp;\u003c/strong\u003eConceptualization, resources, methodology, investigation, data curation, visualization, writing - original draft, review and editing, funding acquisition.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRegula Steinlin Egli\u003c/strong\u003e: Conceptualization, resources, investigation, review and editing, funding acquisition.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeborah R. Vogt\u003c/strong\u003e: Conceptualization, Methodology, formal analysis, data curation, visualization, review, and editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMarcus D\u0026rsquo;Souza\u003c/strong\u003e: review and editing, funding acquisition.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCorresponding Author\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNico Arie Van der Maas, Institute for Physiotherapy Research, Bruegg, Switzerland\u003c/p\u003e\n\u003cp\u003eEmail: [email protected]\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank the study participants, the raters, the \u0026nbsp;involved physiotherapists in recruiting participants and for support on the testing days, Marielle Rutquist for data management, the Department of Clinical research of the University Hospital Basel and University of Basel for their support in the preparation of the study, and the University Hospital for Geriatric Medicine and Rehabilitation Felix Platter in Basel for providing the testing site.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAmatya B, Khan F, La Mantia L, Demetrios M, Wade DT. Non pharmacological interventions for spasticity in multiple sclerosis. Cochrane Database Syst Reviews. 2013. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/14651858.CD009974.pub2\u003c/span\u003e\u003cspan address=\"10.1002/14651858.CD009974.pub2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAsmussen MJ, Mauracher ME, Omu O, Nigg SR, Jarvis SE. Reliability and validity of a novel device for quantifying ankle dorsiflexion force in persons with multiple sclerosis. Mult Scler Relat Disord. 2020. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.msard.2020.101940\u003c/span\u003e\u003cspan address=\"10.1016/j.msard.2020.101940\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBarin L, Salmen A, Disanto G, Babačic H, Calabrese P, Chan A, Kamm CP, Kesselring J, Kuhle J, Gobbi C, Pot C, Puhan MA, von Wyl V. The disease burden of Multiple Sclerosis from the individual and population perspective: Which symptoms matter most? Mult. Scler Relat Disord. 2018. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.msard.2018.07.013\u003c/span\u003e\u003cspan address=\"10.1016/j.msard.2018.07.013\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBarin L, Kaufman M, Salmen A, Kamm CP, Gobbi C, Kuhle J, Pot C, Chan A, Czaplinski A, Ajdacic-Gross V, Rodgers S, Kesselring J, Puhan MA, von Wyl V. Pattern of care for Multiple Sclerosis in a setting of universal care access: a cross-sectional study. Multiple Scler Relat Disorders. 2018. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.msard.2018.11.033\u003c/span\u003e\u003cspan address=\"10.1016/j.msard.2018.11.033\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBarnes MP, Bhakta BB, Moore P, Richardson D, Salisbury C, Thornton H, Turner-Stokes L, Ward A. The management of adults with spasticity using botulinum toxin: A guide to clinical practice. Surrey, UK: Radius Healthcare, Byfleet; 2001.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBarnes MP, Kent RM, Semlyen JK, McMullen KM. Spasticity in multiple sclerosis. Neurorehabil Neural Repair. 2003. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1177/0888439002250449\u003c/span\u003e\u003cspan address=\"10.1177/0888439002250449\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBaschung Pfister P, de Bruin ED, Sterkele I, Maurer B, de Bie RA, Knols RH. Manual muscle testing and hand-held dynamometry in people with inflammatory myopathy: An intra- and interrater reliability and validity study. PLoS ONE 13, e0194531. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1371/journal.pone.0194531\u003c/span\u003e\u003cspan address=\"10.1371/journal.pone.0194531\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBohannon RW. Manual muscle testing: does it meet the standards of an adequate screening test? Clin Rehabil. 2005;19(6):662\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1191/0269215505cr873oa\u003c/span\u003e\u003cspan address=\"10.1191/0269215505cr873oa\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBrotherton EJ, Sabapathy S, Heshmat S, Kavanagh JJ. Voluntary muscle activation in people with multiple sclerosis is reduced across a wide range of forces following maximal effort-fatiguing contractions. J Neurophysiol. 2023;130:1162\u0026ndash;73. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1152/jn.00146.2023\u003c/span\u003e\u003cspan address=\"10.1152/jn.00146.2023\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBrotherton EJ, Sabapathy S, Dempsey LM, Kavanagh JJ. Short-latency afferent inhibition is reduced in people with multiple sclerosis during fatiguing muscle contractions. Eur J Neurosci. 2024;59:2087\u0026ndash;101. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/ejn.16253\u003c/span\u003e\u003cspan address=\"10.1111/ejn.16253\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBye E, Glinsky J, Yeomans J, Hungerford A, Patterson H, Chen L, Harvey L. The inter-rater reliability of the 13-point manual muscle test in people with spinal cord injury. Physiother Theory Pract. 2021;37(10):1126\u0026ndash;31. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/09593985.2019.1685033\u003c/span\u003e\u003cspan address=\"10.1080/09593985.2019.1685033\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eClaros-Salinas D, Dittmer N, Neumann M, Sehle A, Spiteri S, Willmes K, Schoenfeld MA, Dettmers C. Induction of cognitive fatigue in MS patients through cognitive and physical load. Neuropsychol Rehabil. 2013;23:182\u0026ndash;201. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/09602011.2012.726925\u003c/span\u003e\u003cspan address=\"10.1080/09602011.2012.726925\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCrone C, Hultborn H, Jespersen B, Nielsen J. 1987. Reciprocal Ia inhibition between ankle flexors and extensors in man. J. Physiol. 1987;389:163\u0026ndash;185. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1113/jphysil.1987.sp016652\u003c/span\u003e\u003cspan address=\"10.1113/jphysil.1987.sp016652\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDel Blanco JA, Taboada-Iglesias Y. Effects of resistance exercise in patients with spasticity: Systematic review. Apunts Sports Med. 2021;56(212):100356. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.apunsm.2021.100356\u003c/span\u003e\u003cspan address=\"10.1016/j.apunsm.2021.100356\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDe Lima FX, de Araujo Ribeiro-Alvares JB, de Souza Roberti L, Mocellin MP, Baroni BM. Field Hip Stability Isometric Test (F-HipSIT): Reliability of Assessing the Hip Posterolateral Muscle Strength in Sports Settings. Journal of Sport Rehabilitation. 2024;33(6):478\u0026ndash;483. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1123/jsr.2023-0146\u003c/span\u003e\u003cspan address=\"10.1123/jsr.2023-0146\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDibba l. Bewertung der Reliabilit\u0026auml;t des modifizierten manuellen Muskelfunktionstest (mMMT) bei Personen mit Multiple Sklerose nach Schulung der Untersucherinnen 2024. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://webthesis.donau-uni.ac.at/thesen/205077.pdf\u003c/span\u003e\u003cspan address=\"https://webthesis.donau-uni.ac.at/thesen/205077.pdf\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eD\u0026rsquo;Souza M, et al. Electronic Neurostatus-EDSS increases the quality of expanded disability status scale assessments: Experience from two phase 3 clinical trials. Mult Scler. 2020;26(8):993\u0026ndash;6. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1177/1352458519845108\u003c/span\u003e\u003cspan address=\"10.1177/1352458519845108\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEtoom M, Khraiwesh Y, Lena F, Hawamdeh M, Hawamdeh M, Hawamdeh Z, Centonze D, Foti C. Effectiveness of physiotherapy interventions on spasticity in people with multiple sclerosis. Am J Phys Med Rehabil. 2018;97(11):793\u0026ndash;807. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/PHM.0000000000000970\u003c/span\u003e\u003cspan address=\"10.1097/PHM.0000000000000970\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEymir M, Unver B, Karatosun V, Reliability. Concurrent Validity, and Minimal Detectable Change of the Hand-Held Dynamometry for the Assessment of Knee Muscle Strength in Patients With Revision Total Knee Arthroplasty. Arch Phys Med Rehabil. 2024;105(1):34\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.apmr.2023.05.002\u003c/span\u003e\u003cspan address=\"10.1016/j.apmr.2023.05.002\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFlorence JM, Pandya S, King WM, Robison JD, Baty J, Miller JP, Schierbecker J, Signore LC. Intrarater reliability of manual muscle test (Medical Research Council scale) grades in Duchenne's muscular dystrophy. Phys Ther. 1992;72:115\u0026ndash;22. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/ptj/72.2.115\u003c/span\u003e\u003cspan address=\"10.1093/ptj/72.2.115\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFortunato R, van der Maas NA, Biland-Thommen U, Kaufmann M, Sieber C, Kamm CP, Zecca C, Gobbi C, Chan A, Calabrese P, Kesselring J, von Wyl V. Physiotherapy use and access-barriers in persons with multiple sclerosis: A cross-sectional analysis. Mult Scler Relat Disord. 2021;48:102710. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.msard.2020.102710\u003c/span\u003e\u003cspan address=\"10.1016/j.msard.2020.102710\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFrese E, Brown M, Norton BJ. Clinical reliability of manual muscle testing. Middle trapezius and gluteus medius muscles. Phys Ther. 1987;67:1072\u0026ndash;6. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/ptj/67.7.1072\u003c/span\u003e\u003cspan address=\"10.1093/ptj/67.7.1072\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGladman D, et al. Fatigue numeric rating scale validity, discrimination and responder definition in patients with psoriatic arthritis. RMD Open. 2020;6:e000928. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/rmdopen-2019-000928\u003c/span\u003e\u003cspan address=\"10.1136/rmdopen-2019-000928\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHarris-Love M. April. The manual muscle test meeting the challenge of the therapeutic trial 2014. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://moam.info_the_manual_muscle_test_59cf62891723dd8cf17d38d0\u003c/span\u003e\u003cspan address=\"http://moam.info_the_manual_muscle_test_59cf62891723dd8cf17d38d0\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (accessed 18 2021).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHaugh AB, Pandyan AD, Johnson GR. A systematic review of the Tardieu Scale for the measurement of spasticity. Disabil Rehabil. 2006;28:899\u0026ndash;907. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/09638280500404305\u003c/span\u003e\u003cspan address=\"10.1080/09638280500404305\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHayes KW, Falconer J. 1992. Reliability of hand-held dynamometry and its relationship with manual muscle testing in patients with osteoarthritis in the knee. J. Orthop. Sports Phys. Ther. 1992;16:145\u0026ndash;149. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2519/jospt.1992.16.3.145\u003c/span\u003e\u003cspan address=\"10.2519/jospt.1992.16.3.145\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHe J. Stretch reflex sensitivity: effects of postural and muscle length changes. IEEE Trans Rehabil Eng. 1998;6:182\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1109/86.681184\u003c/span\u003e\u003cspan address=\"10.1109/86.681184\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHoang PD, Gandevia SC, Herbert RD. Prevalence of joint contractures and muscle weakness in people with multiple sclerosis. Disabil Rehabil. 2014;36:1588\u0026ndash;93. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3109/09638288.2013.854841\u003c/span\u003e\u003cspan address=\"10.3109/09638288.2013.854841\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHugos CL, Cameron MH. Assessment and measurement of spasticity in MS: State of the evidence. Curr Neurol Neurosci Rep. 2019;19:79. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s11910-019-0991-2\u003c/span\u003e\u003cspan address=\"10.1007/s11910-019-0991-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJ\u0026oslash;rgensen M, Dalgas U, Wens I, Hvid LG. Muscle strength and power in persons with multiple sclerosis - A systematic review and meta-analysis. J Neurol Sci. 2017;376:225\u0026ndash;41. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://dx.doi.org/10.1016/j.jns.2017.03.022\u003c/span\u003e\u003cspan address=\"10.1016/j.jns.2017.03.022\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKakebeeke TH, Lechner H, Baumberger M, Denoth J, Michel D, Knecht H. The importance of posture on the isokinetic assessment of spasticity. Spinal Cord. 2002;40:236\u0026ndash;43. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://dx.doi.org/10.1038/sj.sc.3101282\u003c/span\u003e\u003cspan address=\"10.1038/sj.sc.3101282\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKappos L. Neurostatus scoring: Definitions for a standardised, quantified neurological examination and assessment of Kurtzke's Functional Systems and Expanded Disability Status Scale in multiple sclerosis. Version 04/20.2.2011. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.neurostatus.net/media/specimen/Definitions_0410-2_s.pdf\u003c/span\u003e\u003cspan address=\"http://www.neurostatus.net/media/specimen/Definitions_0410-2_s.pdf\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Accessed 31 July 2025).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKnepler C, Bohannon RW. Subjectivity of Forces Associated with Manual-Muscle Test Grades of 3+, 4-, and 4. Percept Mot Skills. 1998;87(3\u0026ndash;suppl):1123\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2466/pms.1998.87.3f.1123\u003c/span\u003e\u003cspan address=\"10.2466/pms.1998.87.3f.1123\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKnutsson E, M\u0026aring;rtensson A. Dynamic motor capacity in spastic paresis and its relation to prime mover dysfunction, spastic reflexes and antagonist co-activation. Scand J Rehabil Med. 1980;12:93\u0026ndash;106. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.apmr.2006.09.011\u003c/span\u003e\u003cspan address=\"10.1016/j.apmr.2006.09.011\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKoo TK, Li MY. A guideline of selecting and reporting intraclass correlation coefficients for reliability research. J Chiropr Med. 2016;15:155\u0026ndash;63. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jcm.2016.02.012\u003c/span\u003e\u003cspan address=\"10.1016/j.jcm.2016.02.012\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKrause DA, Schlagel SJ, Stember BM, Zoetewey JE, Hollmann JH. Influence of Lever Arm and Stabilization on Measures of Hip Abduction and Adduction Torque Obtained by Hand-Held Dynamometry. Arch Phys Med Rehabil. 2007;88:37\u0026ndash;42. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.apmr.2006.09.011\u003c/span\u003e\u003cspan address=\"10.1016/j.apmr.2006.09.011\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKurzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS) 1983. Neurology;33(11):1444-52. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1212/wnl.33.11.1444\u003c/span\u003e\u003cspan address=\"10.1212/wnl.33.11.1444\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLatzel G, Fischbacher Schrobiltgen E. Multiple Sklerose in der Schweiz. In: Die Lebensbedingungen von MS-Betroffenen und die finanziellen Folgen ihrer Krankheit. Schriftenreihe Schweiz Nr. 13 Z\u0026uuml;rich: Schweizerische MS-Gesellschaft Z\u0026uuml;rich. 2001.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLoy BD, Taylor RL, Fling BW, Horak FB. Relationship between perceived fatigue and performance fatigability in people with multiple sclerosis: A systematic review and meta-analysis. J Psychosom Res. 2017;100:1\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jpsychores.2017.06.017\u003c/span\u003e\u003cspan address=\"10.1016/j.jpsychores.2017.06.017\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMallucci G, et al. Neurostatus-SMARTCARE clinical trial: Enabling health care professionals to assess EDSS for decentralized trials in multiple sclerosis. Multiple Scler J. 2025;31(4):497\u0026ndash;501. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1177/13524585241305966\u003c/span\u003e\u003cspan address=\"10.1177/13524585241305966\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMayer NH. Clinicophysiologic concepts of spasticity and motor dysfunction in adults with an upper motoneuron lesion. Muscle Nerve 1997;Suppl. 6:S1\u0026ndash;S13. PMID: 9826979.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMedical Research Council. Aids to examination of the peripheral nervous system. Memorandum no. 45. London: Her Majesty\u0026rsquo;s Stationary Office; 1976.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMorita H, Crone C, Christenhuis D, Petersen N. Modulation of presynaptic inhibition and disynaptic reciprocal Ia inhibition during voluntary movement in spasticity. Brain. 2001;124(4):826\u0026ndash;37. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/brain/117.5.1161\u003c/span\u003e\u003cspan address=\"10.1093/brain/117.5.1161\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMorris SL, Williams G. A historical review of the evolution of the Tardieu Scale. Brain Inj. 2018;32:665\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/02699052.2018.1432890\u003c/span\u003e\u003cspan address=\"10.1080/02699052.2018.1432890\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNewsome SD, Wang JI, Kang JY, Calabresi PA, Zackowski KM. Quantitative measures detect sensory and motor impairments in multiple sclerosis. J Neurol Sci. 2011;305:103\u0026ndash;11. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jns.2011.03.003\u003c/span\u003e\u003cspan address=\"10.1016/j.jns.2011.03.003\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNg SS, Hui-Chan CW. Contribution of ankle dorsiflexor strength to walking endurance in people with spastic hemiplegia after stroke. Arch Phys Med Rehabil. 2012;93:1046\u0026ndash;51. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.apmr.2011.12.016\u003c/span\u003e\u003cspan address=\"10.1016/j.apmr.2011.12.016\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNielsen J, Sinkjaer T, Toft E, Kagamihara Y. Segmental reflexes and ankle joint stiffness during co-contraction of antagonistic ankle muscles in man. Exp Brain Res. 1994;102:350\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/BF00227521\u003c/span\u003e\u003cspan address=\"10.1007/BF00227521\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNielsen JB, Christensen MS, Farmer SF, Lorentzen J. Spastic movement disorder: should we forget hyperexcitable stretch reflexes and start talking about inappropriate prediction of sensory consequences of movement? Exp. Brain Res. 2020;238:1627\u0026ndash;36. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00221-020-05792-0\u003c/span\u003e\u003cspan address=\"10.1007/s00221-020-05792-0\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOesch P et al. Assessments in der Rehabilitation: Band 2. Bewegungsapparat. 3. \u0026uuml;berarb. u. erw. Auflage. Hogrefe Verlag, Bern. 2017. ISBN 978-3-456-85718-3.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOliveira DG, Oliveira GM, Kirkwood R. Clinimetric Properties of the Applied Kinesiology Manual Muscle Test in Adults With and Without Pain: A Methodological Study. J Chiropr Med. 2022;21(4):260\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jcm.2022.03.003\u003c/span\u003e\u003cspan address=\"10.1016/j.jcm.2022.03.003\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePenner IK, Raselli C, St\u0026ouml;cklin M, Opwis K, Kappos L, Calabrese P. The Fatigue Scale for Motor and Cognitive Functions (FSMC): validation of a new instrument to assess multiple sclerosis-related fatigue. Mult Scler. 2009;15:1509\u0026ndash;17. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1177/1352458509348519\u003c/span\u003e\u003cspan address=\"10.1177/1352458509348519\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePhilips BA, Lo SK, Mastaglia FL. Muscle force measured using break testing with a hand-held myometer in normal subjects aged 20 to 69 years. Arch Phys Med Rehab. 2000;81(5):653\u0026ndash;61. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/s0003-9993(00)90050-9\u003c/span\u003e\u003cspan address=\"10.1016/s0003-9993(00)90050-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eR Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. 2018. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.R-project.org\u003c/span\u003e\u003cspan address=\"http://www.R-project.org\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSchaubert KL, Bohannon RW. Reliability and validity of three strength measures obtained from community-dwelling elderly persons. J Strength Cond Res. 2005;19(3):717\u0026ndash;20. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1519/r-15954.1\u003c/span\u003e\u003cspan address=\"10.1519/r-15954.1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSchwartz S, Cohen ME, Herbison GJ, Shah A. 1992. Relationship between two measures of upper extremity strength: manual muscle test compared to hand-held myometry. Arch. Phys. Med. Rehabil. 1992:73;1063\u0026ndash;1068. PMID: 1444773.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSehle A, M\u0026uuml;ndermann A, Starrost K, Sailer S, Becher I, Dettmers C, Vieten M. Objective assessment of motor fatigue in multiple sclerosis using kinematic gait analysis: a pilot study. J Neuroeng Rehabil. 2011;8:59. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/1743-0003-8-59\u003c/span\u003e\u003cspan address=\"10.1186/1743-0003-8-59\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSeverijns D, Zijdewind I, Dalgas U, Lamers I, Lismont C, Feys P. The assessment of motor fatigability in persons with multiple sclerosis: A systematic review. Neurorehabil Neural Repair. 2017;31:413\u0026ndash;31. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1177/1545968317690831\u003c/span\u003e\u003cspan address=\"10.1177/1545968317690831\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eShindo M, et al. Changes in reciprocal ia inhibition during voluntary contraction in man. Exp Brain Res. 1984;53:400\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/BF00238170\u003c/span\u003e\u003cspan address=\"10.1007/BF00238170\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSpiteri S, Hassa T, Claros-Salinas D, Dettmers C, Schoenfeld MA. Neural correlates of effort-dependent and effort-independent cognitive fatigue components in patients with multiple sclerosis. Mult Scler. 2019;25:256\u0026ndash;66. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1177/1352458517743090\u003c/span\u003e\u003cspan address=\"10.1177/1352458517743090\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSteinlin Egli R. Multiple Sklerose verstehen und behandeln. Berlin Heidelberg New York: Springer-; 2011. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/978-3-642-17633-3\u003c/span\u003e\u003cspan address=\"10.1007/978-3-642-17633-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSteinlin Egli R. Modifizierte Muskelfunktionspr\u0026uuml;fung bei Multipler Sklerose. Berlin: Springer; 2024. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/978-3-662-68029-2\u003c/span\u003e\u003cspan address=\"10.1007/978-3-662-68029-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eStone CA, Nolan B, Lawlor PG, Kenny RA. Hand-held dynamometry: tester strength is paramount, even in frail populations. J Rehabil Med. 2011;43(9):808\u0026ndash;11. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2340/16501977-0860\u003c/span\u003e\u003cspan address=\"10.2340/16501977-0860\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTerwee C, Bot S, de Boer M, van der Windt D, Knol D, Dekker J, et al. Quality criteria were proposed for measurement properties of health status questionnaires. J Clin Epidemiol. 2007;60(1):34\u0026ndash;42. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jclinepi.2006.03.012\u003c/span\u003e\u003cspan address=\"10.1016/j.jclinepi.2006.03.012\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eThompson AJ, Banwell BL, Barkhof F, Carrol WM, Coetzee T, Comi G, Correale J, Fazekas F, Filippi M, Freedman MS, Fujihara K, Galetta SL, Hartung HP, Kappos J, Lublin FD, Marrie RA, Miller AE, Miller DH, Montalban X, Mowry EM, Sorensen PS, Tintor\u0026eacute; M, Traboulsee AL, Trojano M, Uitdehaag BMJ, Vukusic S, Waubant E, Weinshenker BG, Reingold SC, Cohen JA. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018;17:162\u0026ndash;73. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S1474-4422(17)30470-2\u003c/span\u003e\u003cspan address=\"10.1016/S1474-4422(17)30470-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eVan der Maas NA, Biland-Thommen U, Grillo Juszczak T. Die Valididit\u0026auml;t, Reliabilit\u0026auml;t und Akzeptanz des Multiple Sclerosis Questionnaire for Physiotherapists (MSQPT). Physioscience. 2010;5:135\u0026ndash;42.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eVan der Maas NA. Patient-reported questionnaires in MS rehabilitation: responsiveness and minimal important difference of the multiple sclerosis questionnaire for physiotherapists (MSQPT). BMC Neurol. 2017;17:50. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s12883-017-0834-1\u003c/span\u003e\u003cspan address=\"10.1186/s12883-017-0834-1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWagner JM, Kremer TR, Van Dillen LR, Naismith RT. Plantarflexor weakness negatively impacts walking in persons with multiple sclerosis more than plantarflexor spasticity. Arch Phys Med Rehabil. 2014;95:1358\u0026ndash;65. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.apmr.2014.01.030\u003c/span\u003e\u003cspan address=\"10.1016/j.apmr.2014.01.030\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWikholm JB, Bohannon RW. Hand-held Dynamometer Measurements: Tester Strength makes a difference. JOSPT. 1991;13:191\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2519/jospt.1991.13.4.191\u003c/span\u003e\u003cspan address=\"10.2519/jospt.1991.13.4.191\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWood DE, Burridge JH, van Wijck FM, McFadden C, Hitchcock RA, Pandyan AD, Haugh A, Salazar-Torres JJ, Swain ID. Biomechanical approaches applied to the lower and upper limb for the measurement of spasticity: a systematic review of the literature. Disabil Rehabil. 2005;27:19\u0026ndash;32. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/09638280400014683\u003c/span\u003e\u003cspan address=\"10.1080/09638280400014683\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYoung CA et al. Fatigue in amyotrophic lateral sclerosis/motor neuron disease: prevalence, influences and trajectories 2025. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/21678421.2025.2533881\u003c/span\u003e\u003cspan address=\"10.1080/21678421.2025.2533881\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Footnotes","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003e \u003cem\u003eAbbreviations\u003c/em\u003e: CI, confidence interval; FSMC, Fatigue Scale of Motor and Cognition; ICC, intraclass correlation coefficient; mMMT, modified Manual Muscle Test; MS, multiple sclerosis; MTS, Modified Tardieu Scale; NRS, numeric rating scale; pwMS, persons with multiple sclerosis; EDSS, Expanded Disability Status Scale.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Multiple sclerosis, Manual muscle test, Reliability, Fatigue, Spasticity, Physiotherapy","lastPublishedDoi":"10.21203/rs.3.rs-7576603/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7576603/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eMultiple sclerosis (MS) presents various symptoms, such as weakness, spasticity, ataxia, and reduction in sensory function. Traditional manual muscle strength tests may be biased due to the influence of spasticity. The modified Manual Muscle Test (mMMT) for people with MS (pwMS) was developed to take spasticity into consideration. This study aimed to evaluate the intra- and interrater reliability of the mMMT, as well as the influence of fatigue and spasticity on test results.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eSix raters examined 28 pwMS in this single-centre, prospective, cross-sectional, and longitudinal study with a test-retest design. The muscle strength tests for dorsal foot flexion, hip flexion, and elbow flexion were used. Testing and retesting were conducted within 4 hours. Fatigue was assessed using the Fatigue Scale for Motor and Cognitive Functions and a numeric rating scale. Spasticity was evaluated using the Modified Tardieu Scale. The interrater reliability of the mMMT was evaluated by the intraclass correlation coefficient using one-way random effects ANOVA models. The intrarater reliability was estimated using two-way random effects ANOVA models. Models were adjusted for spasticity and rating order as a proxy for fatigue.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eThe interrater reliability of the mMMT was poor. The results varied between raters and muscle groups. However, the intrarater reliability was good (overall intraclass correlation coefficient, 0.77). Fatigue or spasticity did not affect the test results.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eThe mMMT may be a reliable measure of muscle function in MS when applied by the same healthcare professional. We cautiously conclude that it may be possible to test selective muscle function in the presence of spasticity, reducing its influence on muscle strength testing in pwMS. This study also highlights the importance of rater training and the development of test protocols for each muscle group separately.\u003c/p\u003e\u003ch2\u003eTrial Registration\u003c/h2\u003e\u003cp\u003eClinicalTrials.gov ID NCT03603691. Initial registration date 06/19/2018.\u003c/p\u003e","manuscriptTitle":"The reliability of the modified Manual Muscle Test for persons with MS","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-04 11:25:05","doi":"10.21203/rs.3.rs-7576603/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e38f5ad8-677a-42de-9cb0-a166cde75deb","owner":[],"postedDate":"November 4th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-26T08:09:12+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-04 11:25:05","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7576603","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7576603","identity":"rs-7576603","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}