Study to Evaluate the Reliability and Validity of the Modified Manual Muscle Test for Persons With MS
Study to Evaluate the Reliability and Validity of the Modified Manual Muscle Test for Persons With MS
Many patients with multiple sclerosis (MS) are treated with physiotherapy. Muscle weakness is
 a common symptom. It can be evaluated with a variety of muscle function tests. In MS
 patients, testing muscle function can be confounded by many factors, such as spasticity and
 ataxia, which are not considered by the existing tests and may cause biased test results.
 Steinlin Egli described a Modified Manual Muscle Test (MMMT) that considers spasticity and
 may provide a more reliable and valid muscle function test for MS patients.

 The investigators aim to evaluate the inter- and intra-rater reliability of the Modified
 Manual Muscle Test in MS and evaluate the validity of the Modified MMT according to the
 criteria of the 6 level British Medical Research Council (BMRC) manual muscle test and the
 microFET2 handhold dynamometer.
Background In Switzerland, many patients with multiple sclerosis (MS) are treated with
 physiotherapy. Muscle weakness is a common symptom. Particularly in progressive disease
 courses, motor dysfunction is a major contributor to the reduced mobility and quality of
 life. Therefore, improving the motor dysfunction is an important goal for therapy and is
 evaluated with a variety of muscle function tests. The 6 level British Medical Research
 Council (BMRC) manual muscle test is the most widely used test in MS and is a part of the
 Neurostatus-Expanded Disability Status Scale (EDSS) assessment, which has been adopted as the
 standard in most of the pivotal trials that have led to the approval of the current MS
 treatments. In MS patients, testing muscle function can be confounded by many factors, such
 as spasticity and ataxia, which are not considered by the existing tests and may cause biased
 test results. Steinlin Egli described a Modified Manual Muscle Test (MMMT) that considers
 spasticity and may provide a more reliable and valid muscle function test for MS patients.

 Aim of the study is to evaluate the inter- and intra-rater reliability of the Modified Manual
 Muscle Test in MS and evaluate the validity of the Modified MMT according to the criteria of
 the Neurostatus BMRC manual muscle test and the microFET2 handhold dynamometer.

 Methods This is a single-centre, prospective cross-sectional study with a test-retest design.
 The Neurostatus BMRC manual muscle test and the microFET2 hand held dynamometer are used as
 the criteria. The primary endpoint is the ordinal MMMT level. The intra-class correlation
 coefficient (ICC) of the ranked MMMT levels will be estimated. The investigator aims to show
 that the MMMT results are clinically relevant with a high level of ICC.

 The secondary endpoints include the Neurostatus BMRC levels, the muscle strength as measured
 by the microFET2 dynamometer and fatigue using a numeric rating scale (NRS). Subgroup
 analyses will determine whether the MMMT is less sensitive to the influence of spasticity
 than the Neurostatus BMRC.

 28 patients with MS will be tested in 2 days. In each day, six examiners will test seven
 patients in the morning and seven patients in the afternoon. Three MS-therapists from the
 Specialized Group Physiotherapy in MS and three neurologists from the Department of Neurology
 at the University Hospital Basel will be tester. All examiners will be blinded to the results
 of the other examiners. All test persons will be blinded to their test results. First, the
 patient will rate his fatigue using the NRS. Muscle function will be tested with the
 microFET2 and spasticity will be assessed using the modified Tardieu Scale. Then, the first
 round of manual testing will be executed. After each test, there will be a break that is long
 enough for the patients to recuperate. The order of the examiners will be randomized. The
 retest round will proceed in a different order. Finally, spasticity will be tested again
 using the modified Tardieu Scale, and the patients will rate their fatigue.

 Statistical Analysis The study data will be analysed using the internet-based program R. The
 descriptive statistics will describe the sample characteristics. The inter-rater reliability
 will be estimated by the ICC of the MMMT ranks. The ICC will be estimated by a two-way
 random-effects ANOVA and reported with 95% CI. If the lower limit of the CI is larger than
 the pre-specified clinically relevant ICC margin, the MMMT will be considered a reliable tool
 for evaluating muscle strength in MS patients.

 The inter-rater reliability the Neurostatus BMRC will be estimated similarly by the ICC. The
 ICC of both tests will be compared. The test-retest reliability of the MMMT and Neurostatus
 BMRC will be estimated using two-way random-effects ANOVA and will be reported by ICC
 estimates. The influence of potential fatigue will be analysed by plotting the test and
 retest results against the NRS and investigating the associations and interactions using a
 linear mixed effects model. The pairwise correlations of the MMMT and the Neurostatus BMRC
 with the microFET2 will be graphically analysed (scatterplots and/or boxplots), and
 Spearman's ρ will be calculated. The primary and secondary analyses will be repeated for
 subgroups with high and low spasticity patients to compare the sensitivity of the MMMT and
 Neurostatus BMRC to spasticity.

 Expected results: The investigators expect the MMMT for MS to be a reliable and valid manual
 muscle function test that can be used in the evaluation of the long-term treatment of MS
 patients with physical therapy.
Inclusion Criteria

 -  diagnosed with MS according to the McDonald criteria

 -  EDSS between 0 and 6.5

 -  older than 18 years of age.

 Exclusion Criteria:

 -  An acute episode of MS within 3 months prior to the testing,

 -  grave cognitive changes

 -  distinct fatigue

 -  a history of current back, neck or elbow pain