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 ...

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