Muscle and nerve biopsy may be vital diagnostic tools in various neuromuscular disorders. Since these procedures are invasive, it matters to decide when to perform a biopsy, which muscle or nerve to be selected, and how to interpret the pathologies. This review addresses the indications, methods of biopsies, and also significant pathological findings frequently encountered in muscle and nerve pathology.

New therapeutics in neurology are expanding at an unprecedented pace. In addition to the classic enzyme-replacement therapies, monoclonal antibodies are increasingly being used to modulate autoimmunity. RNA therapeutics are an emerging class, together with gene and cell therapies. The nomenclature of international nonproprietary names helps us to recognize these new drugs according to their class and function. Suffixes denote major categories of the drug, while infixes provide additional information such as the source and target.

Muscle pathology findings may guide the diagnosis of neuromuscular disorders since they are helpful for understanding the pathological processes causing muscle weakness and also provide significant clues for the diagnosis of muscle diseases. Recent advances in molecular genetics mean that a muscle biopsy can be omitted when diagnosing inherited muscle diseases. However, the muscle pathology can still play a role in those cases and its findings are also required when diagnosing inflammatory myopathies.

Citations

• Sarcolemmal Excitability Properties of the Trapezius
  Mitchell J. Lycett, James Lee, Robert Boland‐Freitas, Karl Ng
  Muscle & Nerve.2025; 71(4): 600.     CrossRef
• Redox-active metals and oxidative stress–mediated myopathies in Callinectes amnicola, blue crab populations from impacted sites of the Lagos Lagoon: inferences for adverse ecological outcomes
  Azubuike Victor Chukwuka, Fisayo C. Jerome, Adesola Hassan, Benjamin Ebonwu, Aina O. Adeogun
  Environmental Science and Pollution Research.2023; 30(50): 108565.     CrossRef

Acute sarcoid myositis is rarely complicated by sarcoidosis, and steroid therapy is considered the standard treatment. We experienced a patient with acute sarcoid myositis who did not respond to aggressive high-dose corticosteroid therapy, but showed a dramatic improvement after the addition of weekly low-dose oral methotrexate (MTX). This intervention allowed the resumption of normal daily activities after 6 months. Our case strongly suggests that MTX should be considered in patients with acute sarcoid myositis that is resistant to corticosteroid therapy.

Ullrich congenital muscular dystrophy (UCMD) is caused by mutations in one of three genes encoding collagen VI. Although UCMD usually shows an early onset, progressive weakness, contractures and hyperlaxity of the joints, and respiratory failure, it is well known to exhibit a wide spectrum of clinical severities. The severities of the phenotypic subtypes are mainly divided according to the ambulation status. We report a patient with the early-severe phenotype of UCMD who was diagnosed by the detection of novel recessive mutations in COL6A1.

In facioscapulohumeral muscular dystrophy (FSHD), prominent inflammatory cellular infiltrates mimicking inflammatory myopathies are often observed in muscle biopsies. We report extensive inflammatory changes in a 16-year-old girl who was genetically confirmed as to have FSHD. Immunohistochemical staining revealed that this could be clearly distinguished from inflammatory myopathies, both in terms of cell subsets and the expression of antigenic targets. Our observations strongly suggest that the inflammatory cellular infiltrates in FSHD differ from those observed in inflammatory myopathies.

Citations

• The DUX4 protein is a co‐repressor of the progesterone and glucocorticoid nuclear receptors
  Julieta Quintero, Nizar Y. Saad, Sabrina M. Pagnoni, Daniela K. Jacquelin, Laura V. Gatica, Scott Q. Harper, Alberto L. Rosa
  FEBS Letters.2022; 596(20): 2644.     CrossRef
• Interaction between mesenchymal stem cells and myoblasts in the context of facioscapulohumeral muscular dystrophy contributes to the disease phenotype
  Ekaterina Kiseleva, Olesya Serbina, Anna Karpukhina, Vincent Mouly, Yegor S. Vassetzky
  Journal of Cellular Physiology.2022; 237(8): 3328.     CrossRef
• Facioscapulohumeral muscular dystrophy: genetics, gene activation and downstream signalling with regard to recent therapeutic approaches: an update
  Teresa Schätzl, Lars Kaiser, Hans-Peter Deigner
  Orphanet Journal of Rare Diseases.2021;[Epub]     CrossRef

Background
Telbivudine is a nucleoside analogue used for the treatment of chronic hepatitis B, but it often develops mitochondrial toxicity leading to symptomatic myopathy. In this study, three patients with telbivudine induced myopathy were enrolled in order to investigate the nature and pathogenesis of mitochondrial toxicity caused by long-term use of telbivudine.
Methods
Clinical features, laboratory findings, muscle pathology, and quantitation of mitochondrial DNA were studied in three patients.
Results
Patients presented with progressive muscle weakness with high serum creatine kinase levels. Light microscopic findings of muscle pathology showed ragged red fibers that reacted strongly with succinate dehydrogenase stain, but negative for cytochrome c oxidase activities. Electron microscopy revealed abnormal mitochondrial accumulation with rod shaped inclusions. The quantitative peroxidase chain reaction showed a depletion of mitochondrial DNA in skeletal muscle of the patients.
Conclusions
Nucleoside analogues including telbivudine are potent inhibitors of viral DNA polymerases. However, they are not specific for viral DNA and can disturb mitochondrial replication at the same time. All nucleotide analogues should be used with close clinical observation in order to avoid development of mitochondrial myopathy.

Statin is commonly used for lowering cholesterols and can be myotoxic to cause drug-induced necrotizing myopathy. Statininducedmyopathy ranges from asymptomatic hyperCKemia to lethal rhabdomyolysis but is usually reversed by withdrawalof causative drugs. The patient in this study presented with statin-induced necrotizing myopathy, which was finally improvedwith immunosuppressive therapy, but not just with drug withdrawal. Since statin can induce myopathy through autoimmuneprocesses, we should consider using immunomodulating agents in cases with statin-induced myopathy, which is refractoryto drug withdrawal.

Ullrich disease is a rare congenital muscular dystrophy, which is clinically characterized by generalized muscular weakness,distal joint hyperextensibility, proximal joint contractures, protuberant calcanei and high-arched palate. The disease is causedby collagen VI deficiency in interstitum and/or sarcolemma of skeletal muscles, for which mutations either in COL6A1,COL6A2 or COL6A3 are responsible. We report a girl who presented with symptoms typical of Ullrich disease, in whomthe diagnosis was confirmed by immunohistochemistry and molecular genetic study.

Laminopathy is a term designed for the diseases caused by mutations in a gene encoding nuclear envelope proteins, lamin A/C (LMNA). Skeletal muscle laminopathy includes autosomal dominant/ recessive Emery-Dreifuss muscular dystrophies (AD/AR-EDMD) and limb-girdle muscular dystrophy type 1B (LGMD1B), which are clinically characterized by progressive muscular weakness, varying degree of joint contractures and cardiac involvement. Since lamin A/C is believed to maintain nuclear integrity by polymerizing into nuclear lamina, the mutations in LMNA might affect nuclear shape and subsequently alter normal gene expression, especially in skeletal muscles. Our observation using electron microscope to analyze skeletal muscle nuclei of laminopathy supports this notion. It has been shown that nuclei are quite altered in their shapes (e.g. nuclear chain formation, sawtooth deformity and serpentine shape) and chromatin is disorganized in majority of nuclei. Chromatin disorganization occurred also in nuclei of satellite cells, which are precursors of skeletal muscle cells, suggesting that muscle regeneration is disturbed in laminopathy. Furthermore, vacuolar formations are frequently detected nearby nuclei, the consistent finding of which implies that nuclear vacuoles may have a role in the pathogenesis. Despite of significant changes in nuclei, myofibrils are relatively well arranged. Thus, it is concluded that nuclear abnormalities and the disturbed muscle regeneration mainly contribute to the pathogenesis of skeletal muscle laminopathy.