Name: measurements of motor function and other clinical outcome parameters in ambulant children with duchenne muscular dystrophy
Uploaded: 2019-01-12T15:00:00
Description: Watch this Scientific Journal Video about Measurements of Motor Function and Other Clinical Outcome Parameters in Ambulant Children with Duchenne Muscular Dystrophy at JoVE.com

We would like to thank Lars Hintermann for taking part in the demonstration of the motor function measure and timed function tests.

Before recruitment, the study was approved by the local ethics committee [Ethics Committee of the two Basel Cantons (EKBB 63/13)] and the Swiss Drug Agency (Swissmedic 2013DR3151) and registered under ClinicalTrials.gov (NCT01995032).
1. Clinical Assessment of Muscle Function
<ol>
	<li>Motor function measure (MFM)
	<ol>
		<li>Have the patient perform each of the following tasks and score them as shown in Table 1. 
		Note: The MFM contains 32 independent...

<ol>
	<li>Ryder, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+burden,+epidemiology,+costs+and+treatment+for+Duchenne+muscular+dystrophy:+an+evidence+review.">The burden, epidemiology, costs and treatment for Duchenne muscular dystrophy: an evidence review.</a> Orphanet Journal of Rare Diseases. 12 (1), 79 (2017).</li><li>Mazzone, E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Star+Ambulatory+Assessment,+6-minute+walk+test+and+timed+items+in+ambulant+boys+with+Duchenne+muscular+dystrophy.">Star Ambulatory Assessment, 6-minute walk test and timed items in ambulant boys with Duchenne muscular dystrophy.</a> Neuromuscular Disorders. 20 (11), 712-716 (2010).</li><li>Buckon, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Can+Quantitative+Muscle+Strength+and+Functional+Motor+Ability+Differentiate+the+Influence+of+Age+and+Corticosteroids+in+Ambulatory+Boys+with+Duchenne+Muscular+Dystrophy?.">Can Quantitative Muscle Strength and Functional Motor Ability Differentiate the Influence of Age and Corticosteroids in Ambulatory Boys with Duchenne Muscular Dystrophy?.</a> PLoS Currents. 8, (2016).</li><li>B&#233;rard, C., Payan, C., Hodgkinson, I., Fermanian, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=MFM+Collaborative+Study+Group.+A+motor+function+measure+for+neuromuscular+diseases.+Construction+and+validation+study.+Neuromuscular+disorders.">MFM Collaborative Study Group. A motor function measure for neuromuscular diseases. Construction and validation study. Neuromuscular disorders.</a> NMD. 15 (7), 463-470 (2005).</li><li>Vuillerot, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Monitoring+changes+and+predicting+loss+of+ambulation+in+Duchenne+muscular+dystrophy+with+the+Motor+Function+Measure.">Monitoring changes and predicting loss of ambulation in Duchenne muscular dystrophy with the Motor Function Measure.</a> Developmental Medicine &amp; Child Neurology. 52 (1), 60-65 (2010).</li><li>Vuillerot, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Responsiveness+of+the+Motor+Function+Measure+in+Neuromuscular+Diseases.">Responsiveness of the Motor Function Measure in Neuromuscular Diseases.</a> Archives of Physical Medicine and Rehabilitation. 93 (12), 2251-2256 (2012).</li><li>McDonald, C. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+6-minute+walk+test+and+other+clinical+endpoints+in+duchenne+muscular+dystrophy:+Reliability,+concurrent+validity,+and+minimal+clinically+important+differences+from+a+multicenter+study:+Reliability.">The 6-minute walk test and other clinical endpoints in duchenne muscular dystrophy: Reliability, concurrent validity, and minimal clinically important differences from a multicenter study: Reliability.</a> Validity and MCID of 6MWT and other Endpoints in DMD. Muscle &amp; Nerve. 48 (3), 357-368 (2013).</li><li>McDonald, C. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+6-minute+walk+test+as+a+new+outcome+measure+in+Duchenne+muscular+dystrophy.">The 6-minute walk test as a new outcome measure in Duchenne muscular dystrophy.</a> Muscle &amp; Nerve. 41 (4), 500-510 (2010).</li><li>ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=ATS+Statement:+Guidelines+for+the+Six-Minute+Walk+Test.">ATS Statement: Guidelines for the Six-Minute Walk Test.</a> American Journal of Respiratory and Critical Care Medicine. 166 (1), 111-117 (2002).</li><li>Mcdonald, C. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=THE+6-minute+walk+test+and+other+endpoints+in+Duchenne+muscular+dystrophy:+Longitudinal+natural+history+observations+over+48+weeks+from+a+multicenter+study:+6MWT+and+Endpoints+in+DMD.">THE 6-minute walk test and other endpoints in Duchenne muscular dystrophy: Longitudinal natural history observations over 48 weeks from a multicenter study: 6MWT and Endpoints in DMD.</a> Muscle &amp; Nerve. 48 (3), 343-356 (2013).</li><li>Deconinck, N., Dan, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pathophysiology+of+Duchenne+Muscular+Dystrophy:+Current+Hypotheses.">Pathophysiology of Duchenne Muscular Dystrophy: Current Hypotheses.</a> Pediatric Neurology. 36 (1), 1-7 (2007).</li><li>Fischmann, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Quantitative+MRI+and+loss+of+free+ambulation+in+Duchenne+muscular+dystrophy.">Quantitative MRI and loss of free ambulation in Duchenne muscular dystrophy.</a> Journal of Neurology. 260 (4), 969-974 (2013).</li><li>Barnard, A. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Skeletal+muscle+magnetic+resonance+biomarkers+correlate+with+function+and+sentinel+events+in+Duchenne+muscular+dystrophy.">Skeletal muscle magnetic resonance biomarkers correlate with function and sentinel events in Duchenne muscular dystrophy.</a> PLOS ONE. 13 (3), e0194283 (2018).</li><li>Willcocks, R. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Multicenter+prospective+longitudinal+study+of+magnetic+resonance+biomarkers+in+a+large+duchenne+muscular+dystrophy+cohort:+Longitudinal+Muscle+MR+in+DMD.">Multicenter prospective longitudinal study of magnetic resonance biomarkers in a large duchenne muscular dystrophy cohort: Longitudinal Muscle MR in DMD.</a> Annals of Neurology. 79 (4), 535-547 (2016).</li><li>Godi, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Longitudinal+MRI+quantification+of+muscle+degeneration+in+Duchenne+muscular+dystrophy.">Longitudinal MRI quantification of muscle degeneration in Duchenne muscular dystrophy.</a> Annals of Clinical and Translational Neurology. 3 (8), 607-622 (2016).</li><li>Schmidt, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Timed+function+tests,+motor+function+measure,+and+quantitative+thigh+muscle+MRI+in+ambulant+children+with+Duchenne+muscular+dystrophy:+A+cross-sectional+analysis.">Timed function tests, motor function measure, and quantitative thigh muscle MRI in ambulant children with Duchenne muscular dystrophy: A cross-sectional analysis.</a> Neuromuscular Disorders. 28 (1), 16-23 (2018).</li><li>Fischer, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+6-minute+walk+test,+motor+function+measure+and+quantitative+thigh+muscle+MRI+in+Becker+muscular+dystrophy:+A+cross-sectional+study.">The 6-minute walk test, motor function measure and quantitative thigh muscle MRI in Becker muscular dystrophy: A cross-sectional study.</a> Neuromuscular Disorders. 26 (7), 414-422 (2016).</li><li>Govoni, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ongoing+therapeutic+trials+and+outcome+measures+for+Duchenne+muscular+dystrophy.">Ongoing therapeutic trials and outcome measures for Duchenne muscular dystrophy.</a> Cellular and Molecular Life Sciences. 70 (23), 4585-4602 (2013).</li><li>Seferian, A. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Upper+Limb+Strength+and+Function+Changes+during+a+One-Year+Follow-Up+in+Non-Ambulant+Patients+with+Duchenne+Muscular+Dystrophy:+An+Observational+Multicenter+Trial.">Upper Limb Strength and Function Changes during a One-Year Follow-Up in Non-Ambulant Patients with Duchenne Muscular Dystrophy: An Observational Multicenter Trial.</a> PLOS ONE. 10 (2), e0113999 (2015).</li><li>Pane, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Upper+limb+function+in+Duchenne+muscular+dystrophy:+24+month+longitudinal+data.">Upper limb function in Duchenne muscular dystrophy: 24 month longitudinal data.</a> PLOS ONE. 13 (6), e0199223 (2018).</li><li>Wokke, B. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Quantitative+MRI+and+strength+measurements+in+the+assessment+of+muscle+quality+in+Duchenne+muscular+dystrophy.">Quantitative MRI and strength measurements in the assessment of muscle quality in Duchenne muscular dystrophy.</a> Neuromuscular Disorders. 24 (5), 409-416 (2014).</li><li>Arpan, I., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Examination+of+effects+of+corticosteroids+on+skeletal+muscles+of+boys+with+DMD+using+MRI+and+MRS.">Examination of effects of corticosteroids on skeletal muscles of boys with DMD using MRI and MRS.</a> Neurology. 83 (11), 974-980 (2014).</li><li>Hooijmans, M. T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Non-uniform+muscle+fat+replacement+along+the+proximodistal+axis+in+Duchenne+muscular+dystrophy.">Non-uniform muscle fat replacement along the proximodistal axis in Duchenne muscular dystrophy.</a> Neuromuscular Disorders. 27 (5), 458-464 (2017).</li><li>Carlier, P. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Global+T2+versus+water+T2+in+NMR+imaging+of+fatty+infiltrated+muscles:+Different+methodology,+different+information+and+different+implications.">Global T2 versus water T2 in NMR imaging of fatty infiltrated muscles: Different methodology, different information and different implications.</a> Neuromuscular Disorders. 24 (5), 390-392 (2014).</li><li>Morrow, J. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=MRI+biomarker+assessment+of+neuromuscular+disease+progression:+a+prospective+observational+cohort+study.">MRI biomarker assessment of neuromuscular disease progression: a prospective observational cohort study.</a> The Lancet Neurology. 15 (1), 65-77 (2016).</li><li>Hollingsworth, K. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Quantitative+MRI+in+muscular+dystrophy:+An+indispensable+trial+endpoint?.">Quantitative MRI in muscular dystrophy: An indispensable trial endpoint?.</a> Neurology. 83 (11), 956-957 (2014).</li></ol>

Several promising outcome measures have been used in clinical trials in patients with Duchenne muscular dystrophy (DMD). The MFM is a validated and reproducible functional test that involves a detailed examination of crucial motor functions in 32 steps4, while the 6MWT can provide useful information about the patient&#39;s endurance.
All currently validated tests have limitations due to inter- and intra-rater variabilities and all require cooperation of the patient and ...

Outcome measures that reliably reflect treatment response are an essential requirement of successful clinical trials. Due to the rapid development of new therapeutic strategies, stronger effort has been made to define reproducible as well as sensitive methods that monitor clinical outcomes.
Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder and the most common type of muscular dystrophy in children. It is characterized by severe involvement of predominantly the skeletal and heart muscle and a progressive disease course, with loss of ambulation around 8-12 years old and premature death mainly before 30 years old1. Validated tests such as motor function measure and timed function tests are widely accepted as clinical tools for monitoring disease progression, as they assess many aspects of daily life functions. Furthermore, in ambulatory cases, they seem to be more sensitive than quantitative muscle strength measures, which cannot be appropriately performed in weak and non-cooperative patients2,3.
The motor function measure (MFM) assesses functions of the neck, trunk, arm, and leg muscles and abilities such as standing, transferring, and walking. It can even be performed in patients who have lost ambulation, as it reflects three dimensions of motor performance4. The MFM (validated for patients aged 6-60 years with DMD) was evaluated based on the MFM User&#39;s Manual5. It includes 32 items and is divided into three subdomains: D1 (assessment of standing and transfer), D2 (assessment of axial and proximal motor function), and D3 (assessment of distal motor function). All items are scored on a 4-point scale (0-3). The test is validated in neuromuscular disorders and can sufficiently monitor changes in muscle function and predict loss of ambulation. Moreover, it agrees with clinical changes perceived by the treating physicians and patients with DMD6,7. Timed function tests are also commonly used as outcome measures, though they are mainly performed in ambulatory patients. Among these, the 6-minute walk test (6MWT) has received special attention since it shows the highest test-retest reliability, predicts clinical decline and loss of ambulation, and correlates more accurately with muscle function measures compared to quantitative muscle strength measures8,9. The test measures the maximal walking distance of a patient in 6 minutes10. It is guided by two trained professionals, a &#34;follower&#34; who walks 1-2 meters behind the patient, and an &#34;evaluator&#34; who records the time. Other timed function tests have lower test-retest reliability and do not reflect endurance, an important marker of ambulatory function8,9,10,11. These tests include the timed 10-meter run/walk test (10MWT), which measures the best performance of walking/running for a 10-meter distance, and the supine-up time, which measures the ability to stand up from supine position2. The use of the motor function measure and timed function tests as primary and secondary endpoints in clinical trials is justified; however, a major limitation is that none are independent of patient collaboration and the skills of the evaluator.
Quantitative MRI (QMRI) is an objective method to visualize well-described morphological abnormalities of the musculature including edema, muscle degeneration, and increased content of adipose and connective tissue12. The use of MRI as a diagnostic tool in neuromuscular disorders has already been established, but its role in monitoring disease progression and treatment response is still limited to clinical trials. T2-relaxation time is known to be increased in muscle dystrophies due to muscle damage, edema, fatty replacement, and inflammation, and further information about muscle fat content can be extracted through calculation of the mean fat fraction (FF). QMRI has been shown to be a promising biomarker, as measurements have correlated with clinical outcome and disease progression, while a mean fat fraction of 50% predicted loss of ambulation13,14. Moreover, QMRI has been able to detect subclinical changes in patients with stable or even improved outcome measures15,16. QMRI data of extensors muscles has also shown to be meaningful regarding its correlation with clinical outcomes17. QMRI is a non-invasive and sensitive method; nevertheless, its cost and the possibility of reduced compliance in younger children may limit its use.
The reliability of functional tests and QMRI has been previously shown in Becker&#39;s muscular dystrophy18. The aim of this cross-sectional study was to highlight sensitive clinical and radiological outcome measures in ambulant children with DMD, as the need for standardized and disease-specific assessments is increasing in the era of clinical trials in neuromuscular disorders.

<table>
	<tbody>
		<tr>
			<td>Physiotherapy mat</td>
			<td>&#160;-&#160;</td>
			<td>&#160;-&#160;</td>
			<td>should not be slippery; alternatively use a wide examination table</td>
		</tr>
		<tr>
			<td>Cushions</td>
			<td>&#160;-&#160;</td>
			<td>&#160;-&#160;</td>
			<td>&#160;-&#160;</td>
		</tr>
		<tr>
			<td>Table&#160;</td>
			<td>&#160;-&#160;</td>
			<td>&#160;-&#160;</td>
			<td>with adjustable height; it should allow the patient to rest forearms while seated and elbows flexed at 90&#176;</td>
		</tr>
		<tr>
			<td>Chair</td>
			<td>&#160;-&#160;</td>
			<td>&#160;-&#160;</td>
			<td>with adjustable height if possible; it should allow the patient to touch the floor with the feet while seated with the hips and knees flexed at 90&#176;</td>
		</tr>
		<tr>
			<td>Stopwatch</td>
			<td>&#160;-&#160;</td>
			<td>&#160;-&#160;</td>
			<td>&#160;-&#160;</td>
		</tr>
		<tr>
			<td>CD or CD-ROM glued onto a piece of cardboard</td>
			<td>&#160;-&#160;</td>
			<td>&#160;-&#160;</td>
			<td>&#160;-&#160;</td>
		</tr>
		<tr>
			<td>10 coins&#160;</td>
			<td>&#160;-&#160;</td>
			<td>&#160;-&#160;</td>
			<td>dimensions: 20 mm wide and 2 mm thick (10 euro cents or equivalent)</td>
		</tr>
		<tr>
			<td>Lead pencil</td>
			<td>&#160;-&#160;</td>
			<td>&#160;-&#160;</td>
			<td>&#160;-&#160;</td>
		</tr>
		<tr>
			<td>Tennis ball</td>
			<td>&#160;-&#160;</td>
			<td>&#160;-&#160;</td>
			<td>&#160;-&#160;</td>
		</tr>
		<tr>
			<td>Sheets of A4 paper or equivalent&#160;</td>
			<td>&#160;-&#160;</td>
			<td>&#160;-&#160;</td>
			<td>weight: 70-80g</td>
		</tr>
		<tr>
			<td>Clipboard</td>
			<td>&#160;-&#160;</td>
			<td>&#160;-&#160;</td>
			<td>&#160;-&#160;</td>
		</tr>
		<tr>
			<td>Two small traffic cones&#160;</td>
			<td>&#160;-&#160;</td>
			<td>&#160;-&#160;</td>
			<td>&#160;-&#160;</td>
		</tr>
		<tr>
			<td>Tape&#160;</td>
			<td>&#160;-&#160;</td>
			<td>&#160;-&#160;</td>
			<td>for marking arrows and stop&#160;&#160;</td>
		</tr>
		<tr>
			<td>Line traced on the floor</td>
			<td>&#160;-&#160;</td>
			<td>&#160;-&#160;</td>
			<td>2 centimeters wide and 6 meters long</td>
		</tr>
		<tr>
			<td>Corridor</td>
			<td>&#160;-&#160;</td>
			<td>&#160;-&#160;</td>
			<td>indoor, straight, up to 30 meters long&#160;</td>
		</tr>
	</tbody>
</table>

measurements of motor function and other clinical outcome parameters in ambulant children with duchenne muscular dystrophy

While the number of new treatment options tested in patients with Duchenne muscular dystrophy (DMD) is increasing, there is still no defining of the most reliable assessments regarding therapeutic efficacy. We present clinical and radiological outcome measures used in ambulatory patients participating in our trial &#34;Treatment with L-citrulline and metformin in Duchenne muscular dystrophy&#34;. The motor function measure is a validated test in patients with neuromuscular disorders that consists of 32 items and assesses all three dimensions of motor performance including standing and transfer (D1 subscore), axial and proximal motor function (D2 subscore), and distal motor function (D3 subscore). The test shows high intra- and inter-rater variability but only when strictly following guidelines of the materials, examination steps, and calculation of scores. The 6-minute walk test, timed 10-meter walk/run test, and supine-up time are commonly used timed functional tests that also sufficiently monitor changes in muscle function; however, they strongly depend on patient collaboration. Quantitative MRI is an objective and sensitive biomarker to detect subclinical changes, though the examination costs may be a reason for its limited use. In this study, a high correlation between all clinical assessments and quantitative MRI scans was found. The combinational use of these methods provides a better understanding about disease progression; however, longitudinal studies are needed to validate their reliability.

Baseline data of 47 ambulatory male patients (aged 6.5 to 10.8 years) with DMD were analyzed. All patients participated previously in the &#34;Treatment with L-citrulline and metformin in Duchenne muscular dystrophy&#34; study. Patients were enrolled from the University Children&#39;s Hospital Basel and from the patient registries of Switzerland, Germany, and Austria. Except for one patient, who refused to take part in the scanning, MRI of all thigh muscles was performed...

Watch this Scientific Journal Video about Measurements of Motor Function and Other Clinical Outcome Parameters in Ambulant Children with Duchenne Muscular Dystrophy at JoVE.com

Measurements of Motor Function and Other Clinical Outcome Parameters in Ambulant Children with Duchenne Muscular Dystrophy

The aim of this study is to present the most reliable clinical outcome measures and their correlations with quantitative muscle MRI in ambulant patients with Duchenne muscular dystrophy.

While the number of new treatment options tested in patients with Duchenne muscular dystrophy (DMD) is increasing, there is still no defining of the most ...

This method can help answer key questions regarding treatment response and clinical decline overtime in clinical trials for patients with Duchenne Muscular Dystrophy. The main advantages of this technique are its lower dependency on the patient's compliance, and suitability for both ambulatory and nonambulatory patients. Demonstrating the procedure will be Christine Seppi, a trained physiotherapist for motor function measure from the University Children's Hospital Basal.Perform the clinical assessment of motor function, by having the patient complete the following tasks, beginning with him lying down on his back. First, he should hold his head in midline position, and then turn it from one side to the other. In this and all subsequent motions, score the patient on a scale of zero to three, based on performance.Next, have the patient remain laying down with his head in the midline position, and ask him to raise his head and maintain this position. Have him bring one knee up to his chest. Now, with one leg flexed both at the hip and knee at approximately 90 degrees, ask him to place his lower leg parallel to the mat with the foot in plantar flexion.Then, ask him to perform a maximal dorsiflexion of the foot. Next, the patient should place one upper limb beside his body, and bring his hand to the opposite shoulder. Then, still lying down on his back, he should move his lower limbs half flexed, with the feet resting on the mat, slightly apart.Ask him to maintain this position, and raise his pelvis. Next, ask the patient to lie on his back, and then turn over onto his stomach, and free both of his upper limbs. Then, ask him to lie down on his back and then sit up.Continue the clinical assessment with the patient sitting on a mat. First, ask him to maintain the seated position while keeping his hands in contact in front of his trunk. While attempting this procedure, it is important to remember to perform it in the given order to avoid unnecessarily repositioning and exhaustion, and to stick to the recommended examination materials and examination steps.Next, while sitting on the mat, place a tennis ball in front of the patient. He should then touch the ball, and then sit back again. Then, have him sit on the mat with his lower limbs out front, and then stand up.At this point, ask the patient to stand in front of the chair and then to sit down on the chair and maintain the seated position with his body as straight as possible. Now, ask the patient to sit on the chair with his head in complete flexion. Then, ask him to raise his head, and maintain this position.At this point in the assessment, ask the patient to sit on the chair in front of a table with his forearms, but not his elbows, placed on the table. Then, ask him to place both hands on top of his head. Now, with the patient in the same position, place a pencil on the table, and ask him to touch the pencil.Now, place the 10 coins next to his hand, and ask him to pick up coins, and hold them in the same hand. Next, place a CD glued to a piece of cardboard on the table. Ask the patient to place one finger in the center of the CD, and to trace around the edge of the disk with the finger.Now, hold a pencil and a paper on the table, and ask him to pick up the pencil and draw inside the frame. Then, put a sheet of paper in his hands, and ask him to tear the paper at least four centimeters. Next, place a tennis ball next to the patient's hand.Ask him to pick up the ball, raise it, and then turn his hand. Then, place a diagram with pictures on the table, and have the patient place a finger in the center of the diagram on the word start and then place his finger on the drawings. At this point, ask the patient to sit on the chair with arms next to his body, and the table at a distance equivalent to the length of his forearm.Then, ask him to place both hands on the table. Next, ask the patient to sit on equipment adapted to his weight, with both feet on the ground. Then, ask him to stand up.For this part of the assessment, ask the patient to stand with the upper limbs resting on a piece of equipment for support. Then, ask him to release the support and stand straight. Next, ask the patient to take the same position again, using the equipment for support.Then, ask him to release the support and raise one foot. For the rest of the assessment, the patient should stand without any support. Ask him to touch the floor with one hand and then stand up again.Then, ask him to stand and walk 10 steps on his heels. Next, draw a straight line that is about six meters long and two centimeters wide on the floor. Ask the patient to walk along this line.Then, ask the patient to run. Next, ask the patient to stand on one foot without support, with the other foot off the ground. Ask him to hop in place.Finally, ask the patient to squat down, and then stand up again. Once the assessment is complete, calculate the motor function measure sub scores by adding the scores of all the items in that domain, dividing it by the maximum score for the domain, and multiplying by 100. Then, to calculate the total score, add the scores of all 32 items, divide the sum by 96, and multiply it by 100.Here we see images of the motor function measure and six minute walk test, in an eight year old patient with Duchenne Muscular Dystrophy. Numbers in red represent assessment of standing and transfer, and blue and yellow represent assessment of proximal and distal motor function respectively. The first rows represent starting positions, and second rows represent tasks.Here, the starting position of the six minute walk test is illustrated on the left side, while the right side image shows a patient performing the test on a 30 meter corridor, under supervision of a physiotherapist. This figure shows a representative example of the correlation of baseline quantitative MRI data, with motor function tests in two patients with Duchenne Muscular Dystrophy. Patient 1 with more severe clinical involvement assessed by functional tests, including the motor function measure and the six minute walk test, showed prominent fatty degradation of the thigh muscles, particularly of the abductors.Patient 2 had better clinical performance, and showed less pronounced fatty degradation of the abductors. For comparison, clinical assessments and qMRI data of all 47 patients at baseline are represented here. Once mastered, this technique can be done in about 45 minutes in ambulatory patients with Duchenne Muscular Dystrophy, if it is performed properly, and there are no further limitations due to the patient's compliance.Following clinical assessments, objective methods like quantitative muscle MRI can be performed in order to answer additional questions like, subclinical disease progression and their specific treatment. After its development, this technique paved the way for researchers in the field of neuromuscular disorders to perform clinical trials using a sensitive outcome measure that provides reliable information about disease progression, and can predict loss of ambulation. After watching this video, you should have a good understanding on how to perform the motor function measure in a patient with Duchenne Muscular Dystrophy, including assessing standing and transfer, axial and motor function, and distal motor function.Don't forget that factors that could interfere with your test performance should be avoided, such as wearing uncomfortable clothes, or using slippery examination materials. Further, patient may not use any autotic device while performing this procedure.

Research

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Medicine

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