Comparison of strength testing modalities in dysferlinopathy

Natalie F Reash¹, Meredith K James², Lindsay N Alfano¹, Anna G Mayhew², Marni Jacobs^{3

4}, Megan A Iammarino¹, Scott Holsten⁵, Chikako Sakamoto⁶, Takayuki Tateishi⁶, Hiroyuki Yajima⁶, Tina Duong^{7

8

9}, Brittney de Wolf⁷, Richard Gee⁸, Diana X Bharucha-Goebel^{10

11}, Elena Bravver⁵, Madoka Mori-Yoshimura¹², Kate Bushby², Laura E Rufibach¹³, Volker Straub², Linda P Lowes¹; Jain COS Consortium

Affiliations

¹ The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio.
² The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
³ Center for Translational Science, Division of Biostatistics and Study Methodology, Children's National Health System, Washington, DC.
⁴ Pediatrics, Epidemiology and Biostatistics, George Washington University, Washington, DC.
⁵ Neuroscience Institute, Carolinas Neuromuscular/ALS-MDA Center, Carolinas HealthCare System, Charlotte, North Carolina.
⁶ Department of Physical Rehabilitation, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.
⁷ Cooperative International Neuromuscular Research Group, Children's National Health System, Washington, DC.
⁸ Lucile Salter Packard Children's Hospital at Stanford, Neurology, Palo Alto, California.
⁹ Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California.
¹⁰ Department of Neurology Children's National Health System, Washington, DC.
¹¹ National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland.
¹² Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.
¹³ The Jain Foundation, Seattle, Washington.

PMID: 35506767
DOI: 10.1002/mus.27570

Comparison of strength testing modalities in dysferlinopathy

Natalie F Reash et al. Muscle Nerve. 2022 Aug.

. 2022 Aug;66(2):159-166.

doi: 10.1002/mus.27570. Epub 2022 May 20.

Authors

Affiliations

¹ The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio.
² The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
³ Center for Translational Science, Division of Biostatistics and Study Methodology, Children's National Health System, Washington, DC.
⁴ Pediatrics, Epidemiology and Biostatistics, George Washington University, Washington, DC.
⁵ Neuroscience Institute, Carolinas Neuromuscular/ALS-MDA Center, Carolinas HealthCare System, Charlotte, North Carolina.
⁶ Department of Physical Rehabilitation, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.
⁷ Cooperative International Neuromuscular Research Group, Children's National Health System, Washington, DC.
⁸ Lucile Salter Packard Children's Hospital at Stanford, Neurology, Palo Alto, California.
⁹ Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California.
¹⁰ Department of Neurology Children's National Health System, Washington, DC.
¹¹ National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland.
¹² Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.
¹³ The Jain Foundation, Seattle, Washington.

PMID: 35506767
DOI: 10.1002/mus.27570

Abstract

Introduction/aims: Dysferlinopathy demonstrates heterogeneity in muscle weakness between patients, which can progress at different rates over time. Changing muscle strength due to disease progression or from an investigational product is associated with changing functional ability. The purpose of this study was to compare three methods of strength testing used in the Clinical Outcome Study (COS) for dysferlinopathy to understand which method and which muscle groups were most sensitive to change over time.

Methods: Patients were evaluated at each study visit using functional scales, manual muscle testing, and handheld dynamometry (HHD) at all 15 sites. A fixed-frame system (Fixed) was used at a subset of seven sites. Screening and baseline visits were evaluated for reliability. Data over a 1-year period were analyzed to determine sensitivity to change among strength modalities and individual muscle groups.

Results: HHD and Fixed captured significant change across 1 year in summed muscle strength score of four muscle groups (P < .01). Strength summed scores were significantly correlated with functional scales (rho = 0.68-0.92, P < .001). Individual muscle groups, however, showed high levels of variability between visits.

Discussion: Although both HHD and Fixed demonstrate change over 12 months, HHD is a less expensive option that provides data on a continuous scale and may be easier to implement. Due to variability in strength measures, researchers should carefully consider use of strength testing as an outcome and may wish to select functional measures with less variability as clinical trial endpoints.

Keywords: dysferlinopathy; handheld dynamometry; limb girdle muscular dystrophy; outcome measure; strength.

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References

REFERENCES

1. Bashir R, Britton S, Strachan T, et al. A gene related to Caenorhabditis elegans spermatogenesis factor fer-1 is mutated in limb-girdle muscular dystrophy type 2B. Nat Genet. 1998;20:37-42.
1. Liu J, Aoki M, Illa I, et al. Dysferlin, a novel skeletal muscle gene, is mutated in Miyoshi myopathy and limb girdle muscular dystrophy. Nat Genet. 1998;20:31-36.
1. Miyoshi K, Kawai H, Iwasa M, Kusaka K, Nishino H. Autosomal recessive distal muscular dystrophy as a new type of progressive muscular dystrophy. Seventeen cases in eight families including an autopsied case. Brain. 1986;109(Pt 1):31-54.
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Comparison of strength testing modalities in dysferlinopathy

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Comparison of strength testing modalities in dysferlinopathy

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Abstract

References

REFERENCES

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