edicine and Rehabilitation

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Archives of Physical Medicine and Rehabilitation 2013;94:1555-61

ORIGINAL ARTICLE

Responsiveness of the Motor Function Measure inPatients With Spinal Muscular Atrophy

Carole Vuillerot, MD, PhD,a,b,c,d Christine Payan, MD,e Jean Iwaz, PhD,b,c,d,f

Rene Ecochard, MD, PhD,b,c,d,f Carole Berard, MD,a and the MFM Spinal Muscular AtrophyStudy Group

From the aHospices Civils de Lyon, Hopital Femme-Mere-Enfant, L’Escale, Service de Medecine Physique et de Readaptation Pediatrique, Bron;bUniversite de Lyon, Lyon; cUniversite Lyon I, Villeurbanne; dCNRS UMR 5558, Laboratoire de Biometrie et Biologie Evolutive, EquipeBiostatistique Sante, Pierre-Benite; eAssistance Publique-Hopitaux de Paris, Hopital Pitie-Salpetriere, Institute of Myology, Paris; andfHospices Civils de Lyon, Service de Biostatistique, Lyon, France.

Abstract

Objective: To assess the ability of the Motor Function Measure (MFM) to detect changes in the progression of spinal muscular atrophy (SMA).

Design: Observational, retrospective, multicenter cohort study.

Setting: Seventeen departments of pediatric physical medicine.

Participants: Volunteer patients with SMA (NZ112) aged 5.7 to 59 years with no treatment other than physical therapy and nutritional or

respiratory assistance.

Interventions: Not applicable.

Main Outcome Measures: The distributions of the MFM scores (total score and 3 subscores) were analyzed per SMA subtype. The relationships

between scores and age were studied. The slopes of score changes (reflecting MFM responsiveness) were estimated in patients with at least

6 months’ follow-up and 2 MFMs. Hypothetical sample sizes for specific effect sizes in clinical trial scenarios are given.

Results: In 12 patients with SMA type 2 and 19 with SMA type 3 (mean � SD follow-up, 25.8�19mo), there was a moderate inverse relationship

between age and the MFM total score. Patients with less than 6 months’ follow-up showed little score changes. Patients with longer follow-ups

showed a slow deterioration (�0.9 points/y for type 2 and �0.6 points/y for type 3). Substantial responsiveness was obtained with the MFM

Dimension 2 subscore (proximal and axial motricity) in patients with SMA type 2 (standardized response mean [SRM]Z1.29), and with the MFM

Dimension 1 subscore (standing and transfers) in patients with SMA type 3 aged 10 to 15 years (SRMZ.94).

Conclusions: If further confirmed by larger studies, these preliminary results on the relative responsiveness of the MFM in SMAwill foster its use

in monitoring disease progression in patients who participate in clinical trials.

Archives of Physical Medicine and Rehabilitation 2013;94:1555-61

ª 2013 by the American Congress of Rehabilitation Medicine

Spinal muscular atrophy (SMA) is a recessively inherited neuro-muscular disease characterized by a degeneration of the spinalcord motor neurons. The clinical spectrum of SMA is highlyvariable and ranges from early infant death to normal adult life.The severity of muscle weakness depends mainly on the patient’sage at disease onset and, most importantly, on the maximal motormilestone acquired (ability to hold head up, sit, or walk).1 This led

Supported by the Association Francaise contre les Myopathies.

No commercial party having a direct financial interest in the results of the research supporting

this article has or will confer a benefit on the authors or on any organization with which the authors

are associated.

0003-9993/13/$36 - see front matter ª 2013 by the American Congress of Re

http://dx.doi.org/10.1016/j.apmr.2013.01.014

some authors to propose defining SMA stages by the ability to sitor walk.2-5

The recent understanding of the pathogenesis of SMA raisedhopes that specific therapeutic approaches might be possible.6

Many clinical trialsdplanned, in progress, or completeddhavechosen motor function as the primary or secondary outcome.6

Indeed, in children with SMA, motor function assessment toolsappeared to be more reliable than quantitative muscle testing inmonitoring the course of the disease.7,8 Nonetheless, valid andresponsive outcome measures are still needed to assess the effectof a treatment on the motor function of patients with SMA.9,10

habilitation Medicine

1556 C. Vuillerot et al

Today, few clinical outcome measures, except survival, areavailable for patients with SMA type 1, the most severe form ofthe disease.11 Therefore, a motor function measure that allows anassessment of patients with SMA, regardless of the disease type, iswelcome. Validation studies of many scales applied to SMA havealready been publisheddfor example, the Gross Motor FunctionMeasure (GMFM),12 the Hammersmith Functional Motor Scalefor SMA (HFMS),13,14 the Expanded HFMS (ExpHFMS),15,16 andthe Upper Limb Module for Nonambulant SMA Patients.17

However, the validation processes of most scales lack specificresponsiveness assessments (ie, sensitivity to change studies).18

Within the specific context of SMA, the HFMS and theModified HFMS (MoHFMS)19 are used only in nonambulantpatients with SMA types 2 and 3. The 6-minute walk test is nowroutinely used to assess patients with neuromuscular diseases,especially Duchenne muscular dystrophy and SMA. Althoughconvenient and useful in patients with SMA type 3,20 this testbecomes useless when ambulation is lost during follow-up,especially during a clinical trial. The ExpHFMS has added13 items from the GMFM to capture various aspects of ambula-tion. Its reliability and validity have been validated in SMA types2 and 3,15 but the methodology used for its construction has beenthe object of some criticism.18 The Motor Function Measure(MFM) is a reliable tool designed for most of the neuromusculardiseases and is applicable to a wide range of disease severities inambulant and nonambulant patients between 6 and 60 years ofage.21 The MFM showed good convergent validity and excellentcorrelations with the Vignos, Brooke, and FIM scales, as well aswith a visual analog scale of overall motor impairment used bysome physicians.21 The preliminary results concerning respon-siveness in a population of 152 patients with various neuro-muscular diseases (of whom 15 had SMA) showed goodresponsiveness, especially in Duchenne muscular dystrophy.22,23

The aim of the present study was to monitor motor functionimpairment in patients with SMA types 1, 2, and 3 using the MFMin order to study the responsiveness of the MFM in this diseaseand provide estimations of the number of patients with SMAneeded for clinical trials to prove the effectiveness of a given drug.

Methods

Participants

For the present study, data were collected from patients followedup in 17 departments of pediatric physical medicine located inFrance, Belgium, and Switzerland. These centers use the MFM inthe everyday management of patients with a wide variety ofneuromuscular diseases, and their physiotherapists were given

List of abbreviations:

ExpHFMS Expanded HFMS

GMFM Gross Motor Function Measure

HFMS Hammersmith Functional Motor Scale for SMA

MFM Motor Function Measure

MFM D1 Motor Function Measure, Dimension 1 subscore

MFM D2 Motor Function Measure, Dimension 2 subscore

MFM D3 Motor Function Measure, Dimension 3 subscore

MoHFMS Modified HFMS

SMA spinal muscular atrophy

SMN survival motor neuron

SRM standardized response mean

specific training in administering the MFM with a high interraterreliability.21 The protocol of the study was approved by the ethicscommittee of Hospices Civils de Lyon on June 26, 2009.

The inclusion criteria were as follows: (1) patients older than 5years at first MFM testing; (2) a clinical diagnosis of SMA type 1, 2,or 3 with laboratory confirmation of a mutation of the survival motorneuron (SMN) gene; (3) at least 1 MFM testing by a trained phys-iotherapist during routine follow-up; and (4) no treatment other thanphysical therapy, nutritional assistance, and respiratory assistance.

In the present study, in agreement with the International SMAConsortium,1,24 SMA is classified into 3 clinical types: (1) SMAtype 1 (severe) with onset between birth and 6 months of age(patients unable to sit without support and/or death occurringusually before 2y of age), (2) SMA type 2 (intermediate) with onsetbefore 18 months of age (patients able to sit but unable to stand orwalk unaided and/or death occurring usually after 2y of age); and(3) SMA type 3 (mild) with onset after 18 months of age (patientsable to stand and walk and/or death occurring in adulthood).

Motor Function Measure-32

The MFM-32 consists of 32 task items in 3 dimensions thatprovide a detailed profile of the physical impairment: D1, standingand transfers; D2, axial and proximal motor function; and D3,distal motor function. The scoring of each task uses a 4-pointLikert scale based on the subject’s maximal abilities withoutassistance: 0, cannot initiate the task or maintain the startingposition; 1, performs the task partially; 2, performs the taskincompletely or imperfectly (with compensatory/uncontrolledmovements or slowness); and 3, performs the task fully and“normally.” The 32 scores are summed to yield a total scoreexpressed as the percentage of the maximum possible score (theone obtained with no physical impairment); the lower the totalscore, the more severe the impairment.

In routine follow-up of patients with neuromuscular diseases,the MFM scores of each patient are automatically reported by thephysiotherapist on a specific scoring sheet allowing a longitudinalfollow-up. Furthermore, the cooperation of the patients is alsorated as null, moderate, or optimal.

Data collection

By the end of 2009, the scores of MFM tests administered to 112patients in the 17 centers between 2005 and June 30, 2008, werecollected by a clinical research assistant. For each patient,a specific clinical questionnaire was filled out from the medicalrecords; it included detailed information on motor deteriorationmilestones (eg, loss of ambulation, defined as the inability to walk10 steps without assistance).

Statistical analysis

The MFM scores were presented as mean, SD, and range per SMAtype and walking ability. The relationship between the MFM totalscore and age at first visit was analyzed in patients with SMAtypes 2 and 3 by using regression modeling. The assumption ofhomogeneity of the regression slopes was tested using an analysisof covariance.

The responsiveness was studied according to the SMA type (intypes 2 and 3) by analyzing the slopes of change in patients with atleast 6 months’ follow-up. Precisely, for each patient, the repeated

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Use of Motor Function Measure in spinal muscular atrophy 1557

measurements of the MFM total score and the subscores weresummarized by a slope of change expressed as an annual rateusing the unweighted least-square estimate.25 These slopes werethen expressed as standardized response means (SRMs) bycalculating the ratios of the mean slopes to their SDs.26 TheseSRM values were considered high if >.80, moderate if rangingfrom .50 to .79, and low if <.50.27 These estimations helped incalculating the number of patients needed in a clinical trial todetect various outcome differences with various statistical powers.

Results

Patients’ characteristics

A total of 112 subjects (61 males, 51 females) with geneticallyconfirmed SMA were evaluated. Their characteristics and MFMscores by SMA type are displayed in table 1. Among patients withSMA type 3, 16 lost the ability to walk between the ages of 3 and28 years (mean � SD: 12.1�5.4y). Patients’ cooperation wasrated optimal in 90% of type 2 and 80% of type 3 patients.

Figure 1 shows the total MFM scores at first MFM testingaccording to age. A first finding from this figure is that there areareas where the scores of patients of different disease typesoverlap. Another finding is that the regression lines that fit thetotal scores of patients with SMA types 2 and 3 show a slowdecrease with age. A third finding is that the lines that fit the totalscores of patients with SMA types 2 and 3 (equations: MFM totalscore Z [�.85 � age] þ 49.77 and MFM total score Z [�.67 �age] þ 82.65, respectively) are almost parallel. This may beconsidered as a trend toward similar disease progressions alongtime in patients with SMA types 2 and 3 (analysis of covarianceslope test PZ.71). The number of patients with SMA type 1 wasnot sufficient to generate a reliable regression line.

MFM responsiveness

Overall, 164 MFM tests were carried out, and 40 patients wereassessed at least twice. The mean � SD follow-up duration was21.6�18.8 months (range, 1.1e66.4mo). The number of patientsanalyzed for responsiveness was 31, with a mean � SD follow-upof 25.8�18.9 months.

Table 1 Patients’ characteristics and MFM scores according to SMA ty

Variable SMA Type 1

Participants 9

Males 6

Age (y) 10.2�2.7 (7.4e15.4)

Range of follow-up (mo) 3.6e28.8

Follow-up >6mo 1

Patients with at least 2 MFM 3

Patients with more than 2 MFM 1 with 3 MFM

Optimal cooperation 6/6

MFM scores

D1 2.3�2.4 (0e7.7)

D2 30.9�19.5 (5.6e72.2)

D3 42.9�24.7 (9.5e90.5)

Total 21.9�12.8 (7.3e47.9)

NOTE. Values are n, mean � SD (range), or as otherwise indicated.

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The scores of patients with short follow-ups (<6mo) showedlittle variation. Table 2 shows the slopes of change of the scores ofpatients with long follow-ups (>6mo) according to the SMA type.As expected, the slopes of change of the MFM total score in thelatter patients showed slow deterioration: �0.9�1.45 points peryear for patients with SMA type 2 (mean age � SD, 9.67�3.24y),�0.6�4.0 points per year for all patients with SMA type 3 (meanage � SD, 21.15�14.14y), and �2.9�3.3 for patients with SMAtype 3 aged 10 to 15 years (mean age � SD, 12.6�1.9y).

Figure 2 shows the changes in individual MFM subscore D2according to age in patients with SMA type 2. These changesindicate a substantial responsiveness of this subscore in thesepatients (�3.25�2.52 points/y, SRMZ1.29).

Figure 3 shows the changes in individual MFM subscore D1according to age in patients with SMA type 3. Here again, thechanges indicate a substantial responsiveness of this subscore,especially in patients with SMA type 3 aged 10 to 15 years(�6.22�6.59 points/y, SRMZ.94). As for the improvement foundin several adult patients with SMA type 3 (nZ6), we may evoke2 nonexclusive causes linked to the first MFM: (1) a learningeffect; and (2) a motivation to get more exercise. However, thesecases had only 2 assessments; thus, longer follow-ups are neededto obtain better estimates of motor function progression.

Estimation of the number of subjects to include ina clinical trial

Table 3 shows the estimated number of patients needed fora clinical trial to demonstrate the beneficial effect of a giventreatment according to the desired effect of a 1-year active treat-ment versus placebo, statistical power, and alpha risk. Forexample, with 80% power and a 5% alpha risk, a stabilization ofmotor function would require 2 groups of 12 patients with SMAtype 2 using the D2 subscore. In SMA type 3, 2 groups of 55patients would be needed with the D1 subscore.

If half the decrease in motor function in the treatment groupversus the placebo group is to be reached, with 80% power and5% alpha risk, 2 groups of 45 patients with SMA type 2 would beneeded using the D2 subscore. In patients with SMA type 3, 2groups of 210 patients would be needed with the D1 subscore.

pes

SMA Type 2 SMA Type 3

44 59

24 31

11.5�5.0 (5.7e27) 18.7�12.3 (6.2e59)

2e62.4 1.2e66

12 19

14 23

9 with 3 MFM

3 with 4 MFM

2 with 3 MFM

1 with 4 MFM

34/38 38/47

3.3�3.8 (0e23.1) 40.2�29.4 (0e100)

57.6�21.0 (13.9e94.4) 87.8�20.0 (11.1e100)

76.6�12.8 (38.1e100) 94.43�9.53 (42.9e100)

40.0�11.4 (14.6e66.7) 70.1�18.8 (14.6e93.8)

y = -0.85x + 49.77

y = -0.67x + 82.65

0

20

40

60

80

100

120

0 10 20 30 40 50 60 70

MF

M To

ta

l s

co

re

Age (years)

Fig 1 The lines fitting the first MFM total score according to age in

patients with SMA type 2 (dark squares) and type 3 (clear dots).

Patients with SMA type 1 (gray triangles) are represented without

fitting line.

1558 C. Vuillerot et al

Discussion

The present results tend to confirm that SMA is a single diseaseentity with variable presentations and that it consists of a continuousspectrum of severities rather than clearly separated types. First, therewere age ranges (8e12y and 17e19y) within which the total MFMscore was not reliably able to distinguish between patients withSMA type 2 and type 3 (ie, where high-score patients with type 2and low-score patients with type 3 were intermingled). Second,these scores decreased almost in parallel with age. Thus, theproportion of patients with disease features intermediate betweenthe 2 types might not be negligible. Some patients with SMA type 1,all receiving assisted ventilation, have prolonged survival. In termsof pure classification (Munsat or Dubowitz), these patients are, infact, of SMA “type 1b,” at borderline with type 2; that is, they werenever able to sit. The study did not consider patients with 2 differentsubtypes of SMA type 3 (3a and 3b). These subtypes certainly havedifferent functional outcomes and progression rates,20 but thesample size was not large enough to consider this distinction.

Table 2 Slopes of change in patients with >6 months’ follow-up

Variable SMA Type 2

Participants 12

Age (y) 9.67�3.24 (5.75e16)

Follow-up (mo) 37�20

D1 score

Slope (points/y) �0.18�0.90

SRM 0.2

D2 score

Slope (points/y) �3.25�2.52

SRM 1.29

D3 score

Slope (points/y) 1.93�3.81

SRM 0.51

Total score

Slope (points/y) �0.86�1.45*

SRM 0.6

NOTE. Values are n, mean � SD (range), mean � SD, or as otherwise indicat

* Significant changes, SRM>0.6.

The classification of SMA has been amended to reflect thenatural history of the disease, but this does not seem to have fullysucceeded. According to a number of authors,3 all attempts toclassify a disease are artificial, and classifications do not alwayscorrespond to pathophysiologic realities. The current classificationof SMA should be used with caution for prognosis because the ageat death is mainly influenced by exogenous factors such aspulmonary infections or inadequate medical care. Actually, theInternational Conference on SMA Standard of Care came to theconsensus that the most appropriate care for patients with SMAshould be tailored according to their current functional statusrather than to the disease type.4

The MFM allows the use of the same outcome measure in allpatients with SMA whatever the disease type, whereas fewoutcome measures11 other than survival are available in patientswith extreme muscle weakness, such as those with SMA type 1 ortype 2. Myometry, the HFMS, or the MoHFMS are reliable inpatients with SMA types 2 and 3 but not in those with type 1. The6-minute walk test and other timed tests are not appropriate innonambulant patients; they are applicable only to patients withSMA type 3. The recent module by Mazzone et al,17 specificallydesigned to assess upper limb function in nonambulant patientswith SMA, complements the current scales used in very weakSMA patients with severe contractures in the lower limbs, but stillneeds further validity and responsiveness studies.

We agree with a recent opinion that SMA is a gradual processof muscular atrophy and weakness.4 Our results confirm this view,with significant decreases in MFM subscore D2 in patients withSMA type 2, and in MFM subscore D1 in ambulant patients withSMA type 3 at ages of loss of ambulation (10e15y). Thus,depending on the desired outcome, we consider it mandatory toanalyze all MFM subscores and not only the total score. In specificconditions, such as in ambulant patients with no major statuschange, the D1 subscore will be more sensitive to change whilethe others will remain stable. Subscore D2 shows good respon-siveness in patients with type 2 SMA, and subscore D1 showsgood responsiveness in patients with type 3. In clinical trials, wepropose to use only the subscores that show interesting changes

SMA Type 3

All Ages

SMA Type 3

10e15y

19 10

21.15�14.14 (8e29) 12.6�1.9 (10e14.58)

18.5�14 22�19

�1.95�6.98 �6.22�6.59

0.28 0.94

0.71�3.73 �0.72�2.69

0.19 0.27

�0.13�4.53 �0.52�4.41

0.03 0.12

�0.55�3.99* �2.91�3.33*

0.14 0.87

ed.

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Table 3 Numbers of subjects needed in a clinical trial according

to SMA type, study power, and expected effect

SMA Type

80% Power 90% Power

50%* None 50%* None

SMA type 2

D2 subscore 45y 12 60y 16

Total score 175 45 235 60

SMA type 3

D1 subscore 210 55 280 70

Total score 615 175 820 235

* Expected reduction in MFM score by an active treatment versus

placebo during a 1-year treatment.y Estimated number of subjects per arm. The a risk is .05.

0

10

20

30

40

50

60

70

80

90

100

0 5 10 15 20 25 30

MF

M D

2 su

bsc

ore

Age (years)

Fig 2 Change in MFM D2 subscore according to age in 14 patients

with SMA type 2.

Use of Motor Function Measure in spinal muscular atrophy 1559

within shorter times (ie, D2 in SMA type 2 or D1 in SMA type 3).Distal motor function remains relatively preserved until the latestages of the disease; thus, subscore D3 seems the least usefulsubscore in patients with SMA.

Several authors28-32 have already described the slow decline inmotor function over time and related it to a loss of muscle strength.33

On the contrary, others related the deterioration in motor function toincreased body size, contractures, and scoliosis without an increasein power to cope with these extra demands.30,31 Iannaccone et al34

reported that none of their patients lost strength but that they hadsome loss ofmotor function during the observation period. In a recentobservational study35 of 71 patients with SMA types 2 and 3, theauthors found no detectable mean change in motor function over the12-month follow-up period as measured by the GMFM, the HFMS,or the ExpHFMS; they suggested a nonprogressive or a stable courseof the disease. That conclusion is not consistent with the presentresults. One reason for the divergence could be an insufficientresponsiveness (sensitivity to change) of the measures used to detectchange. A longer follow-up of the patients is also needed to check thedisease progression rate. We believe the individual course of thedisease is probably not a slow continuousworsening but a successionof stable and worsening phases. One argument is that, in our sample,especially in patients with SMA type 3, the age range of 10 to 15years was a crucial period during which the disease exacerbated themost; that is, the loss of motor function was the most obvious(�6.22�6.6 points/y on average for D1), and indeed, the loss ofambulation is often reported to occur 10 years after the disease onset.

0

10

20

30

40

50

60

70

80

90

100

0 5 10 15 20 25 30 35 40 45 50

MF

M D

1 S

ub

sco

re

Age (years)

Fig 3 Change in MFM D1 subscore according to age in 23 patients

with SMA type 3. Gray lines correspond to ambulant patients and black

lines to nonambulant ones.

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The use of the MFM in our sample of patients with SMA wasrather satisfactory despite the inclusion of patients with importantmuscle weakness. Indeed, patient cooperation was high whateverthe SMA type, and there was no relationship between diseaseseverity and the time required to complete the test. In previousindependent investigations, the average MFM-32 test completiontime in 34 patients with SMA aged �6 years was 39 minutes, andthe average for the MFM-20 in 21 patients with SMA aged 2 to 6years was 26 minutes. For comparison’s sake, O’Hagen et al15

reported that completion times for the ExpHFMS were between20 minutes and 1 hour.

Studying changes in motor function in SMA has becomeincreasingly important in light of future clinical trials. The reliablemeasurement of these changes over more than 1 year using theMFM (expressed as an annual rate of change) allowed us to esti-mate the number of subjects needed for a clinical trial according tothe SMA type (though a disputed notion), the expected progress,and the desired study power. However, the above estimated samplesizes might be underestimated and should be compared with thoseprovided by trials with placebo groups, because improved care toparticipating patients might change the expected rate of motorfunction decline. Also, even though the MFM total score was foundto be less responsive than the MFM subscores, it is worth using asa first overall indicator of motor function impairment, and in phaseIII studies, it will capture a wide range of severities and differentrates of disease progression.

Study limitations

One limitation of this study is its retrospective nature. However, itshowed interesting results because the patients were not treatedand because increasing numbers of patients are being included inclinical trials while the measurement tools are still scarce.A Rasch analysis was not performed to evaluate the consistency ofthe MFM in the present study of patients with SMA because thesample size was not sufficient to yield conclusive results. Fatigueis a nonnegligible clinical aspect in patients with SMA that mayinterfere significantly with the completion of the MFM over nearly30 minutes and sometimes up to 45 minutes or more. To bettercapture potential fatigue, some researchers have proposed to timethe MFM, but at present, there is no specific procedure that takesthis duration into account. However, in future large clinical trials,it is hoped that MFM duration and patient management betweenmeasures will be better controlled and that randomization willbalance these and other factors. Besides, one may notice that somepatients have reached the maximum subscores. This does interfere

1560 C. Vuillerot et al

with the objective of the present study because, past thismaximum, the status of a given patient is deemed unable toimprove; it can only worsen. Then subscores D1 and D2 may stillbe used in SMA types 3 and 2, respectively, to monitor stateimprovement after a given therapeutic intervention.

This small sample size and the very slow progress of the diseaserequire that this preliminary study be extended in size and time fora more robust generalizability and power calculations for futureclinical trials. At present, a large MFM database is collecting datafrom many centers in France and abroad, which will soon furthertest the validity and sensitivity to change of the MFM in untreatedpatients with SMA on a larger cohort. This will make it possible tocarry out a specific analysis in every disease type. Finally, althoughwe acknowledge a possible relationship between the SMN2 copynumber and functional limitation, this copy number was notconsidered in the present study because of a lack of data.

Conclusions

In this investigation of the appropriateness of the MFM to assessthe progression of motor function in SMA, the measure was ableto show slight deteriorations in patients followed up more than6 months, and 2 of its subscores were particularly responsive inpatients with SMA types 2 and 3 during the period close to theloss of ambulation. The MFM is thus a good candidate amongvery few tools able to monitor disease progression in patients withSMA presenting with a wide range of disease severity whoparticipate in clinical trials. Further studies will extend the presentpromising results to other neuromuscular diseases.

Keywords

Clinical trial; Mobility limitation; Muscle weakness; Muscularatrophy, spinal; Neuromuscular diseases; Rehabilitation

Corresponding author

Carole Vuillerot, MD, PhD, L’Escale, Service central de reedu-cation, Hopital Femme Mere Enfant, F-69677, Bron, France.E-mail address: carole.vuillerot@chu-lyon.fr.

Acknowledgments

We thank the Association Francaise contre les Myopathies fortheir help in collecting data. We also thank the members of theMFM Spinal Muscular Atrophy Study Group who carried out theMFM tests. The group is composed of the following French,Swiss, and Belgian medical doctors and physical therapistsimplicated in the validation of the MFM in spinal muscularatrophy: A. Renders, MD, D. Laridant, MD, V. Kinet, SRP(Cliniques Universitaires St. LUC, Bruxelles); V. Sperhrs-Ciaffi,MD (Consultation neuromusculaire pediatrique du CHUV, Lau-sanne), M. Fournier-Mehouas, MD, H. Rauscent, MD, V. Tanant,SRP (Hopital de l’Archet, Nice); F. Rumeau, MD, I. Mugnier,SRP, C. Capello, MD (Hopital Brabois, Nancy); D. Fort, MD,M. Desingue, SRP (Centre de Reeducation Enfants, Flavigny surMoselle); I. Hodgkinson, MD, PhD, J.P. Vadot, MD, S. Fontaine,MD, C de Lattre, MD, F. Margirier, SRP, D. Vincent-Genod, SRP,A. Berruyer SRP, Y. Chartier, SRP (l’Escale, Hopital femme mereenfant, Lyon); J. Lachanat, MD, D. Denis, SRP (Fondation

Richard, Lyon); A. Fares, MD, G. Le Claire, MD, J.L. Le Guiet,MD, D. Lefeuvre-Brule, SRP (Centre de Kerpape, Ploemeur);J.Y. Mahe, MD, C. Nogues, SRP (Centre de Pen Bron, LaTurballe); M.C. D’Anjou, MD, L. Feasson, MD, A. Jouve, SRP(Hopital Bellevue, Saint Etienne); J.A. Urtizberea, MD, PhD,D. Salicio, SRP (Hendaye), C. Themar Noel, MD, A. Canal, SRP,G. Ollivier, SRP (Institut de Myologie, Hopital Pitie-Salpetriere,Paris); S. Quijano, MD, PhD, N. Pelligrini, MD, N. Vedrenne,SRP, S. Morel-Lelu, SRP (Hopital Raymond Poincare, Garches);A. Tapin-Durufle, MD, F. Letanoux, SRP (Centre HospitalierRegional Pontchaillou,Rennes); V. Bourg,MD,B.Moulis-Wyndels,SRP (Centre Paul Dottin, Ramonville Saint Agne); M. Marpeau,MD, F. Barthel, MD, D. Trabaud, SRP, D. Rouif, SRP, M. Ver-caemer, SRP (Centre St Jean de Dieu, Paris); V. Tiffereau,MD, PhD,G. Viet, MD, B. Degroote, SRP (Hopital Swinghedaw, Lille);A. Carpentier, MD, I. Bourdeauducq, SRP (Centre Marc Sautelet,Villeneuve d’Ascq); M.C. Commare, MD, M. Mahot, SRP,V. Farigoule, SRP (Centre Hospitalier de Grenoble, Grenoble).

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