Spatio-temporal gait differences in facioscapulohumeral muscular dystrophy during single and dual task overground walking - A pilot study
Background: Facioscapulohumeral muscular dystrophy (FSHD) is a rare genetic muscle disorder leading to progressive muscle loss over time. Research indicates that this progressive muscular atrophy can negatively impact spatio-temporal gait characteristics, but this is not always the case during early-onset or mild cases of the disease. In addition, the performance of a secondary task during overground walking may elucidate greater deficits in spatio-temporal characteristics of gait. However, such dual task effects on FSHD gait have not been studied thus far.
Aim: The current study aimed to (a) quantify changes in spatio-temporal gait parameters in individuals with FSHD using the Tekscan Strideway gait mat system, (b) measure the dual task (DT) effects on cadence and gait velocity during single task (ST) and DT overground walking in FSHD and healthy controls and (c) investigate the correlation between the gait parameters and the methylation status in FSHD.
Methods: Nine FSHD (M±SD=52.78±14.69 years) and nine nearly matched healthy controls (M±SD=50.11±16.18 years) performed five ST and five DT walking in a pseudo-randomized order. The DT included a serial 7’s subtraction task from a random number between 50 and 100. Dependent variables: Cadence (steps/min) and gait velocity (cm/sec) were obtained from Tekscan Strideway (30 Hz, Boston, MA).
Results: The pairwise comparison indicated that cadence was significantly different for both ST (P<0.004) and DT (P<0.02) where FSHD showed lower cadence compared to controls. Gait velocity was also significantly lower for FSHD during ST (P<0.004) and DT (P<0.008). Multilevel modeling (MLM) approach revealed a group by task interaction for cadence (P<0.05) and gait velocity (P<0.001). The interaction showed a significant difference between ST and DT in controls for cadence and gait velocity. However, there was no difference between ST and DT in FSHD. Finally, a comparison of methylation percentage versus gait parameters revealed a significant negative correlation coefficient for cadence but not for gait velocity.
Conclusion: These results indicate specific pairwise differences in both ST and DT walking, observed in the gait parameters as decreased cadence and gait velocity during ST and DT. In addition, the MLM showed that controls exhibited the DT cost as expected but FSHD did not for cadence and gait velocity.
Relevance for Patients: ST appears to be sufficiently challenging in FSHD and results in overall declines in spatio-temporal characteristics of gait. Further research is needed to test this paradigm with early-onset or mild cases to track disease progression and its effects on ambulation.
[1] Hamel J, Tawil R. Facioscapulohumeral Muscular Dystrophy: Update on Pathogenesis and Future Treatments. Neurotherapeutics 2018;15:863-71.
[2] Statland J, Tawil R. Facioscapulohumeral Muscular Dystrophy. Neurol Clin 2014;32:721-8.
[3] Tawil R, Van Der Maarel SM. Facioscapulohumeral Muscular Dystrophy. Muscle Nerve 2006;34:1-15.
[4] Aprile I, Padua L, Iosa M, Gilardi A, Bordieri C, FruscianteR, et al. Balance and Walking in Facioscapulohumeral Muscular Dystrophy: Multiperspective Assessment. Eur J Phys Rehabil Med 2012;48:393-402.
[5] Rijken NH, van Engelen BG, Geurts AC, Weerdesteyn V. Dynamic Stability during Level Walking and Obstacle Crossing in Persons with Facioscapulohumeral Muscular Dystrophy. Gait Posture 2015;42:295-300.
[6] Danckworth F, Karabul N, Posa A, Hanisch F. Risk Factors for Osteoporosis, Falls and Fractures in Hereditary
Myopathies and Sporadic Inclusion Body Myositis a Cross Sectional Survey. Mol Genet Metab Rep 2014;1:85-97.
[7] Lamperti C, Fabbri G, Vercelli L, D’Amico R, Frusciante R, Bonifazi E, et al. A Standardized Clinical Evaluation
of Patients Affected by Facioscapulohumeral Muscular Dystrophy: The FSHD Clinical Score. Muscle Nerve 2010;42:213-7.
[8] Kan HE, Scheenen TW, Wohlgemuth M, Klomp DW, van Loosbroek-Wagenmans I, Padberg GW, et al. Quantitative MR Imaging of Individual Muscle Involvement in Facioscapulohumeral Muscular Dystrophy. Neuromuscul Disord 2009;19:357-62.
[9] Olsen DB, Gideon P, Jeppesen TD, Vissing J. Leg Muscle Involvement in Facioscapulohumeral Muscular Dystrophy Assessed by MRI. J Neurol 2006;253:1437-41.
[10] Tawil R, McDermott MP, Mendell JR, Kissel J, Griggs RC. Facioscapulohumeral Muscular Dystrophy (FSHD):
Design of Natural History Study and Results of Baseline Testing. FSH-DY Group. Neurology 1994;44:442-6.
[11] Petek LM, Rickard AM, Budech C, Poliachik SL, Shaw D, Ferguson MR, et al. A Cross Sectional Study of Two
Independent Cohorts Identifies Serum Biomarkers for Facioscapulohumeral Muscular Dystrophy (FSHD). Neuromuscul Disord 2016;26:405-13.
[12] Rahimov F, King OD, Leung DG, Bibat GM, Emerson CP Jr., Kunkel LM, et al. Transcriptional Profiling in Facioscapulohumeral Muscular Dystrophy to Identify Candidate Biomarkers. Proc Natl Acad Sci U S A 2012;109:16234-9.
[13] Yao Z, Snider L, Balog J, Lemmers RJ, Van Der Maarel SM, Tawil R, et al. DUX4-Induced Gene Expression is the Major Molecular Signature in FSHD Skeletal Muscle. Hum Mol Genet 2014;23:5342-52.
[14] Hamel J, Johnson N, Tawil R, Martens WB, Dilek N, McDermott MP, et al. Patient-Reported Symptoms in
Facioscapulohumeral Muscular Dystrophy (PRISMFSHD). Neurology 2019;93:e1180-92.
[15] Eichinger K, Heatwole C, Iyadurai S, King W, Baker L, Heininger S, et al. Facioscapulohumeral Muscular
Dystrophy Functional Composite Outcome Measure. Muscle Nerve 2018;58:72-8.
[16] Rijken NH, van Engelen BG, Weerdesteyn V, Geurts AC. Clinical Functional Capacity Testing in Patients with
Facioscapulohumeral Muscular Dystrophy: Construct Validity and Interrater Reliability of Antigravity Tests.
Arch Phys Med Rehabil 2015;96:2201-6.
[17] Statland J, Bruetsch A, Huisinga J. An Instrumented Timed up and go is Sensitive to Progression in Facioscapulohumeral Dystrophy (S23.005). Neurology 2019;92:S23.005.
[18] Huisinga J, Bruetsch A, Currence M, Herbelin L, Jawdat O, Pasnoor M, et al. Wireless Sensors to Measure Walking in Patients with Facioscapulohumeral Muscular Dystrophy (FSHD) (P3.123). Neurology 2016;86:123.
[19] Eichinger K, Heatwole C, Heininger S, Stinson N, Stock CM, Grosmann C, et al. Validity of the 6 Minute
Walk Test in Facioscapulohumeral Muscular Dystrophy. Muscle Nerve 2017;55:333-7.
[20] Moreno FI, Mendioroz MI, Poza JJ, Martí JF, de Munain López A. Analysis of Gait and Movement of Upper Limbs in Muscular Dystrophies. Neurologia 2005;20:341-8.
[21] Huisinga J, Bruetsch A, Mccalley A, Currence M, Herbelin L, Jawdat O, et al. An Instrumented Timed up and
go in Facioscapulohumeral Muscular Dystrophy. Muscle Nerve 2018;57:503-6.
[22] Al-Yahya E, Dawes H, Smith L, Dennis A, Howells K, Cockburn J. Cognitive Motor Interference While Walking: A Systematic Review and Meta-analysis. Neurosci Biobehav Rev 2011;35:715-28.
[23] Plummer-D’Amato P, Altmann LJ, Reilly K. Dual-task Effects of Spontaneous Speech and Executive Function on Gait in Aging: Exaggerated Effects in Slow Walkers. Gait Posture 2011;33:233-7.
[24] Smith E, Cusack T, Blake C. The Effect of a Dual Task on Gait Speed in Community Dwelling older Adults: A Systematic Review and Meta-analysis. Gait Posture 2016;44:250-8.
[25] Howell DR, Osternig LR, Chou LS. Dual-task Effect on Gait Balance Control in Adolescents with Concussion.
Arch Phys Med Rehabil 2013;94:1513-20.
[26] Plotnik M, Giladi N, Hausdorff JM. Bilateral Coordination of Gait and Parkinson’s Disease: The Effects of Dual Tasking. J Neurol Neurosurg Psychiatry 2009;80:347-50.
[27] Spildooren J, Vercruysse S, Desloovere K, VandenbergheW, Kerckhofs E, Nieuwboer A. Freezing of Gait in Parkinson’s Disease: The Impact of Dual-tasking and Turning. Mov Disord 2010;25:2563-70.
[28] Verhaeghen P, Steitz DW, Sliwinski MJ, Cerella J. Aging and Dual-task Performance: a Meta-analysis. Psychol Aging 2003;18:443-60.
[29] Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, et al. Montreal Cognitive
Assessment. PsycTESTS Dataset; 2014.
[30] Thomas S, Reading J, Shephard RJ. Revision of the Physical Activity Readiness Questionnaire (PAR-Q). Can
J Sport Sci 1992;17:338-45.
[31] Stevens JA. The STEADI Tool Kit: A Fall Prevention Resource for Health Care Providers. IHS Prim Care Provid
2013;39:162-6.
[32] Iverson GL, Lanting SC, Saffer BY, Koehle MS. Clinical Utility of the PROMIS®-57 Health Outcome Measures. Arch Clin Neuropsychol 2013;28:586-6.
[33] Nikolic A, Jones TI, Govi M, Mele F, Maranda L, Sera F, et al. Interpretation of the Epigenetic Signature
of Facioscapulohumeral Muscular Dystrophy in Light of Genotype-Phenotype Studies. Int J Mol Sci 2020;21:2635.
[34] Sidlauskaite E, Le Gall L, Mariot V, Dumonceaux J. DUX4 Expression in FSHD Muscles: Focus on Its mRNA
Regulation. J Pers Med 2020;10:73.
[35] Jones TI, Yan C, Sapp PC, McKenna-Yasek D, Kang PB, Quinn C, et al. Identifying Diagnostic DNA Methylation Profiles for Facioscapulohumeral Muscular Dystrophy in Blood and Saliva Using Bisulfite Sequencing. Clin Epigenetics 2014;6:23.
[36] Wickham H. ggplot2: Elegant Graphics for Data Analysis. Berlin: Springer; 2016.
[37] Hox JJ, Moerbeek M, van de Schoot R. Multilevel Analysis: Techniques and Applications. 3rd ed. Milton
Park, Abingdon-on-Thames: Routledge; 2017.
[38] Bates D, Mächler M, Bolker B, Walker S. Fitting Linear Mixed-Effects Models using lme4. arXiv 2014;2014:5823.
[39] Kuznetsova A, Brockhoff PB, Christensen RH. LmerTest Package: Tests in Linear Mixed Effects Models. J Stat
Softw 2017;82:1-26.
[40] Ricci E, Galluzzi G, Deidda G, Cacurri S, Colantoni L, Merico B, et al. Progress in the Molecular Diagnosis of
Facioscapulohumeral Muscular Dystrophy and Correlation between the Number of KpnI Repeats at the 4q35 Locus and Clinical Phenotype. Ann Neurol 1999;45:751-7.
[41] Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, et al. The Montreal Cognitive Assessment, MoCA: A Brief Screening Tool for Mild Cognitive Impairment. J Am Geriatr Soc 2005;53:695-9.
[42] Jones TI, King OD, Himeda CL, Homma S, Chen JC, Beermann ML, et al. Individual Epigenetic Status of the
Pathogenic D4Z4 Macrosatellite Correlates with Disease in Facioscapulohumeral Muscular Dystrophy. Clin Epigenetics 2015;7:37.