Rippling muscle disease (RMD) is caused by dominant mutations of the caveolin-3 gene (CAV3), and presents with overlapping limb-girdle muscle weakness, elevated creatine kinase (hyper- CKemia), RMD, and distal myopathy. We report a patient with a CAV3 mutation who presented with myalgia, exercise-induced muscle stiffness, hyperCKemia, and percussion-induced rapid muscle contraction and muscle mounding. A familial genetic study revealed the same mutation in two family members, with physical examinations showing that both of them had rippling muscles.

AGel amyloidosis is an autosomal dominantly inherited disease caused by a GSN mutation, and affected patients typically present with the clinical triad of corneal lattice dystrophy, progressive cranial neuropathy, and cutis laxa. We report a Korean family with AGel amyloidosis with predominant manifestations of facial and bulbar muscle weakness. Whole-exome sequencing revealed a common missense mutation (p.Asp214Tyr) in GSN. This case strongly suggests that AGel amyloidosis should be considered when a patient presents with progressive facial and bulbar palsies.

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.

X-linked Charcot Marie Tooth disease type 1 (CMTX1) is a clinically heterogenous X-linked hereditary neuropathy caused by mutation of the gene encoding gap junction beta 1 protein (GJB1). Typical clinical manifestations of CMTX1 are progressive weakness or sensory disturbance due to peripheral neuropathy. However, there have been some CMTX1 cases with accompanying central nervous system (CNS) manifestations. We report the case of a genetically confirmed CMTX1 patient who presented recurrent transient CNS symptoms without any symptom or sign of peripheral nervous system involvement.

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

Focal eosinophilic myositis (FEM) is the most limited form of eosinophilic myositis that commonly affects the muscles of the lower leg without systemic manifestations. We report a patient with FEM who was studied by magnetic resonance imaging and muscle biopsy with a review of the literature.

Citations

• Origins and functions of eosinophils in two non-mucosal tissues
  Katie S. Day, Lucas Rempel, Fabio M. V. Rossi, Marine Theret
  Frontiers in Immunology.2024;[Epub]     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.

Background
The standardized autonomic function test has become widely available. However, there are no reference data for this test for the Korean population. This study explored reference data for sudomotor and cardiovagal function tests for the Korean population.
Methods
The sweat volume by quantitative sudomotor axon reflex test, heart-rate response to deep breathing (HRdb), expiration:inspiration (E:I) ratio, and Valsalva ratio (VR) were measured in 297 healthy Korean volunteers aged from 20 to 69 years. Multivariate regression analysis was performed to evaluate the effects of age, sex, and body mass index on these variables. The 2.5th, 5th, 10th, 90th, 95th, and 97.5th percentile values were obtained for each investigation.
Results
The sweat volume was higher in males than in females. The HRdb and E:I ratio were negatively correlated with age, and were higher in males than in females. The VR was negatively correlated with age, but it was not correlated with sex.
Conclusions
This study has provided data on the reference ranges for sudomotor and cardiovagal function tests in healthy Korean adults.

Citations

• Abnormal quantitative sudomotor axon reflex test results in patients with tinnitus as a possible indicator of small fiber neuropathy
  Hye Lim Lee, Hyun Ji Lyou, Jae-Jun Song, Chi Kyung Kim
  Frontiers in Neurology.2024;[Epub]     CrossRef
• Generalized anhidrosis with preganglionic sudomotor dysfunction in Fabry disease: a case report
  Eun Bin Cho, Seung Joo Kim, Tae-Won Yang, Heejeong Jeong, Changhyo Yoon, Seunguk Jung, Ki-Jong Park
  Clinical Autonomic Research.2021; 31(4): 585.     CrossRef
• Interpretation of Autonomic Function Test
  Kee Hong Park, Eun Hee Sohn
  Journal of the Korean Neurological Association.2021; 39(2): 61.     CrossRef

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.

Some patients with leprosy may present with atypical features, such as isolated peripheral neuropathy without skin lesions, or marked proprioceptive dysfunction. We report a 56-year-old female who presented with predominant proprioceptive loss without skin lesion, but was finally confirmed as leprous neuropathy by sural nerve biopsy. It is postulated that large myelinated fibers were affected by chronic immunological reactions triggered by inactive bacterial particles, producing a peripheral neuropathy presenting as predominant proprioceptive sensory loss without typical skin lesions.

For the last decades, molecular genetics has achieved great advances that the genes on the list of inherited muscle diseasesare piling up. Those diseases of overlapping clinico-pathologic findings are now understood with discrete molecularpathogeneses. We are facing an exciting era that the long-waited gene therapy may eventually come true. Skipping of dystrophinexon 51 is on successful clinical trials, which will benefit about 13% of the children suffering from Duchenne musculardystrophy. Exon skipping is under active investigation to expand the candidates. Hopefully it may cover majority ofDuchenne muscular dystrophy mutations and some of other diseases. Adeno-associated virus is one of the most versatiletools for gene transfer. It may overcome the limitation of exon skipping. Here we review exon skipping technique ofDuchenne muscular dystrophy and briefly discuss the other strategies being studied to cure inherited muscle diseases.