Muscle Biopsy Evaluation in Neuromuscular Disorders

Joyce, Nanette C.; Oskarsson, Björn; Jin, Lee Way

doi:10.1016/j.pmr.2012.06.006

Cited by 143 publications

(118 citation statements)

References 24 publications

Supporting

Mentioning

114

Contrasting

Unclassified

Order By: Relevance

“…Thorough discussions of those diagnostic technologies are reviewed in the following three articles. 5,37,43 …”

Section: Discussionmentioning

confidence: 99%

“…37 Nerve biopsies are somewhat useful in the characterization of more severe hereditary motor and sensory neuropathies, congenital hypomyelinating neuropathy, and neuroaxonal dystrophy. In addition, perineural immune complex deposition seen in some autoimmune neuropathies, or changes consistent with vasculitis may also be useful diagnostically.…”

Section: Laboratory Evaluationsmentioning

confidence: 99%

“…Ankle dorsiflexors are weaker than ankle plantar flexors, ankle everters are weaker than ankle inverters, knee extensors are weaker than knee flexors, hip extensors are weaker than hip flexors, and hip abductors are weaker than hip adductors. 48 Molecular genetic studies to confirm DMD are summarized by Arnold and Flanigan 5 in this issue, and muscle biopsy immunohistochemistry is summarized by Joyce and collegues 37 in this issue.…”

Section: Myopathiesmentioning

confidence: 99%

See 2 more Smart Citations

Clinical Approach to the Diagnostic Evaluation of Hereditary and Acquired Neuromuscular Diseases

McDonald¹

2012

Physical Medicine and Rehabilitation Clinics of North America

View full text Add to dashboard Cite

SYNOPSIS In the context of a neuromuscular disease diagnostic evaluation, the clinician still must be able to obtain a relevant patient and family history and perform focused general, musculoskeletal, neurologic and functional physical examinations to direct further diagnostic evaluations. Laboratory studies for hereditary neuromuscular diseases include relevant molecular genetic studies. The EMG and nerve conduction studies remain an extension of the physical examination and help to guide further diagnostic studies such as molecular genetic studies, and muscle and nerve biopsies. All diagnostic information needs to be interpreted not in isolation, but within the context of relevant historical information, family history, physical examination findings, and laboratory data, electrophysiologic findings, pathologic findings, and molecular genetic findings if obtained.

show abstract

“…Thorough discussions of those diagnostic technologies are reviewed in the following three articles. 5,37,43 …”

Section: Discussionmentioning

confidence: 99%

Section: Laboratory Evaluationsmentioning

confidence: 99%

Section: Myopathiesmentioning

confidence: 99%

See 1 more Smart Citation

Clinical Approach to the Diagnostic Evaluation of Hereditary and Acquired Neuromuscular Diseases

McDonald¹

2012

Physical Medicine and Rehabilitation Clinics of North America

View full text Add to dashboard Cite

show abstract

“…We used the presence of pyknotic nuclear clumps (also known as nuclear bags) as an indicator of long‐term neurogenic atrophy (Joyce et al . ), and this was assessed by an experienced pathologist who identified and counted pyknotic nuclei as deeply basophilic nuclear clumps.…”

Section: Methodsmentioning

confidence: 99%

Fidelity of muscle fibre reinnervation modulates ageing muscle impact in elderly women

Sonjak

Jacob

Morais

et al. 2019

The Journal of Physiology

View full text Add to dashboard Cite

Key points Susceptibility to age‐related muscle atrophy relates to the degree of muscle denervation and the capacity of successful reinnervation. However, the specific role of denervation as a determinant of the severity of muscle aging between populations with low versus high physical function has not been addressed. We show that prefrail/frail elderly women exhibited marked features of muscle denervation, whereas world class octogenarian female master athletes showed attenuated indices of denervation and greater reinnervation capacity. These findings suggest that the difference in age‐related muscle impact between low‐ and high‐functioning elderly women is the robustness of the response to denervation of myofibers. Abstract Ageing muscle degeneration is a key contributor to physical frailty; however, the factors responsible for exacerbated vs. muted ageing muscle impact are largely unknown. Based upon evidence that susceptibility to neurogenic impact is an important determinant of the severity of ageing muscle degeneration, we aimed to determine the presence and extent of denervation in pre‐frail/frail elderly (FE, 77.9 ± 6.2 years) women compared to young physically inactive (YI, 24.0 ± 3.5 years) females, and contrast these findings to high‐functioning world class octogenarian female masters athletes (MA, 80.9 ± 6.6 years). Muscle biopsies from vastus lateralis muscle were obtained from all three groups to assess denervation‐related morphological and transcriptional markers. The FE group displayed marked grouping of slow fibres, accumulation of very small myofibres, a severe reduction in type IIa/I size ratio, highly variable inter‐subject accumulation of neural cell adhesion molecule (NCAM)‐positive myofibres, and an accumulation of pyknotic nuclei, indicative of recurring cycles of denervation/reinnervation and persistent denervation. The MA group exhibited a smaller decline in type IIa/I size ratio and fewer pyknotic nuclei, accompanied by a higher degree of type I fibre grouping and larger fibre group size, suggesting a greater reinnervation of denervated fibres. Consistent with this interpretation, MA had higher mRNA levels of the reinnervation‐promoting cytokine fibroblast growth factor binding protein 1 (FGFBP1) than FE. Our results indicate that the muscle of FE women has significant neurogenic atrophy, whereas MA muscle exhibit superior reinnervation capacity, suggesting that the difference in age‐related muscle impact between low‐ and high‐functioning elderly women is the robustness of the response to denervation of myofibres.

show abstract

“…First, muscle biopsies can be invasive and discomforting for patients. The process of obtaining a muscle biopsy can also be complicated, as it requires coordination between several health specialists (i.e., surgeon, pathologist, lab personnel) as well as the use of specialized cryopreservation techniques, as opposed to preservation in formalin which is routinely done with other tissue biopsies [22]. Additionally, the amount of primary muscle cells obtained via biopsy is limited and these cells display poor proliferative ability [23], resulting in low reproducibility of experimental analysis due to lack of available sample.…”

Section: Introductionmentioning

confidence: 99%

Direct Reprogramming of Human DMD Fibroblasts into Myotubes for In Vitro Evaluation of Antisense-Mediated Exon Skipping and Exons 45–55 Skipping Accompanied by Rescue of Dystrophin Expression

Lee

Saito

Duddy

et al. 2018

Methods in Molecular Biology

View full text Add to dashboard Cite

Antisense oligonucleotide-mediated exon skipping is a promising therapeutic approach for the treatment of various genetic diseases and a therapy which has gained significant traction in recent years following FDA approval of new antisense-based drugs. Exon skipping for Duchenne muscular dystrophy (DMD) works by modulating dystrophin pre-mRNA splicing, preventing incorporation of frame-disrupting exons into the final mRNA product while maintaining the open reading frame, to produce a shortened-yet-functional protein as seen in milder Becker muscular dystrophy (BMD) patients. Exons 45-55 skipping in dystrophin is potentially applicable to approximately 47% of DMD patients because many mutations occur within this "mutation hotspot." In addition, patients naturally harboring a dystrophin exons 45-55 in-frame deletion mutation have an asymptomatic or exceptionally mild phenotype compared to shorter in-frame deletion mutations in this region. As such, exons 45-55 skipping could transform the DMD phenotype into an asymptomatic or very mild BMD phenotype and rescue nearly a half of DMD patients. In addition, this strategy is potentially applicable to some BMD patients as well, who have in-frame deletion mutations in this region. As the degree of exon skipping correlates with therapeutic outcomes, reliable measurements of exon skipping efficiencies are essential to the development of novel antisense-mediated exon skipping therapeutics. In the case of DMD, researchers have often relied upon human muscle fibers obtained from muscle biopsies for testing; however, this method is highly invasive and patient myofibers can display limited proliferative ability. To overcome these challenges, researchers can generate myofibers from patient fibroblast cells by transducing the cells with a viral vector containing MyoD, a myogenic regulatory factor. Here, we describe a methodology for assessing dystrophin exons 45-55 multiple skipping efficiency using antisense oligonucleotides in human muscle cells derived from DMD patient fibroblast cells.

show abstract

Muscle Biopsy Evaluation in Neuromuscular Disorders

Cited by 143 publications

References 24 publications

Clinical Approach to the Diagnostic Evaluation of Hereditary and Acquired Neuromuscular Diseases

Clinical Approach to the Diagnostic Evaluation of Hereditary and Acquired Neuromuscular Diseases

Fidelity of muscle fibre reinnervation modulates ageing muscle impact in elderly women

Direct Reprogramming of Human DMD Fibroblasts into Myotubes for In Vitro Evaluation of Antisense-Mediated Exon Skipping and Exons 45–55 Skipping Accompanied by Rescue of Dystrophin Expression

Contact Info

Product

Resources

About