Search results for "Myotonia"
showing 10 items of 15 documents
Netrin-1 receptor antibodies in thymoma-associated neuromyotonia with myasthenia gravis.
2017
Objective:To identify cell-surface antibodies in patients with neuromyotonia and to describe the main clinical implications.Methods:Sera of 3 patients with thymoma-associated neuromyotonia and myasthenia gravis were used to immunoprecipitate and characterize neuronal cell-surface antigens using reported techniques. The clinical significance of antibodies against precipitated proteins was assessed with sera of 98 patients (neuromyotonia 46, myasthenia gravis 52, thymoma 42; 33 of them with overlapping syndromes) and 219 controls (other neurologic diseases, cancer, and healthy volunteers).Results:Immunoprecipitation studies identified 3 targets, including the Netrin-1 receptors DCC (deleted i…
Towards development of a statistical framework to evaluate myotonic dystrophy type 1 mRNA biomarkers in the context of a clinical trial
2020
AbstractMyotonic dystrophy type 1 (DM1) is a rare genetic disorder, characterised by muscular dystrophy, myotonia, and other symptoms. DM1 is caused by the expansion of a CTG repeat in the 3’-untranslated region of DMPK. Longer CTG expansions are associated with greater symptom severity and earlier age at onset. The primary mechanism of pathogenesis is thought to be mediated by a gain of function of the CUG-containing RNA, that leads to trans-dysregulation of RNA metabolism of many other genes. Specifically, the alternative splicing (AS) and alternative polyadenylation (APA) of many genes is known to be disrupted. In the context of clinical trials of emerging DM1 treatments, it is important…
Increased Muscleblind levels by chloroquine treatment improve myotonic dystrophy type 1 phenotypes in in vitro and in vivo models
2019
Myotonic dystrophy type 1 (DM1) is a life-threatening and chronically debilitating neuromuscular disease caused by the expansion of a CTG trinucleotide repeat in the 3′ UTR of the DMPK gene. The mutant RNA forms insoluble structures capable of sequestering RNA binding proteins of the Muscleblind-like (MBNL) family, which ultimately leads to phenotypes. In this work, we demonstrate that treatment with the antiautophagic drug chloroquine was sufficient to up-regulate MBNL1 and 2 proteins in Drosophila and mouse (HSA LR ) models and patient-derived myoblasts. Extra Muscleblind was functional at the molecular level and improved splicing events regulated by MBNLs in all disease models. In vivo,…
miR-23b and miR-218 silencing increase Muscleblind-like expression and alleviate myotonic dystrophy phenotypes in mammalian models
2018
Functional depletion of the alternative splicing factors Muscleblind-like (MBNL 1 and 2) is at the basis of the neuromuscular disease myotonic dystrophy type 1 (DM1). We previously showed the efficacy of miRNA downregulation in Drosophila DM1 model. Here, we screen for miRNAs that regulate MBNL1 and MBNL2 in HeLa cells. We thus identify miR-23b and miR-218, and confirm that they downregulate MBNL proteins in this cell line. Antagonists of miR-23b and miR-218 miRNAs enhance MBNL protein levels and rescue pathogenic missplicing events in DM1 myoblasts. Systemic delivery of these “antagomiRs” similarly boost MBNL expression and improve DM1-like phenotypes, including splicing alterations, histo…
Therapeutic Potential of AntagomiR-23b for Treating Myotonic Dystrophy
2020
Myotonic dystrophy type 1 (DM1) is a chronically debilitating, rare genetic disease that originates from an expansion of a noncoding CTG repeat in the dystrophia myotonica protein kinase (DMPK) gene. The expansion becomes pathogenic when DMPK transcripts contain 50 or more repetitions due to the sequestration of the muscleblind-like (MBNL) family of proteins. Depletion of MBNLs causes alterations in splicing patterns in transcripts that contribute to clinical symptoms such as myotonia and muscle weakness and wasting. We previously found that microRNA (miR)-23b directly regulates MBNL1 in DM1 myoblasts and mice and that antisense technology (“antagomiRs”) blocking this microRNA (miRNA) boost…
Internalized myofiber capillaries: Observations on their origin and clinical features
1989
Internalized capillaries limited to type 1 muscle fibers were noted in seven patients. They occurred in each case in association with a similar admixture of neurogenic and myopathic features that included atrophic and hypertrophic fibers, internal nuclei, fiber splitting, and endomyseal and perimyseal fibrosis. Internalized capillaries in enlarged type 1 fibers arose from fiber splits on step section study of four patients. They occurred in the gastrocnemius, quadriceps, and soleus muscles from patients with a variety of disorders that included Becker dystrophy, diabetes mellitus and strenuous leg activities, Achilles tendon rupture, and myotonic dystrophy. Exercise-induced myalgias were no…
Magnetic stimulation study in patients with myotonic dystrophy
1997
To further define motor nervous system alterations in myotonic dystrophy (MD), motor potentials to transcranial and cervical magnetic stimulation (MEPs) were recorded from the right abductor pollicis brevis muscle in 10 patients with MD and in 10 healthy controls. Cortical and cervical latencies, central motor conduction time (CMCT), stimulus threshold intensity and cortical MEP amplitudes expressed both as absolute values and as %M were analysed. MEP cervical latency, absolute or relative amplitude and excitability threshold did not significantly differ in patients and controls. The mean cortical motor latency and CMCT were significantly prolonged in MD patients with respect to normal subj…
Isometric muscle contractions after double pulse stimulation. comparison of healthy subjects and patients with myotonic dystrophy.
1996
Isometric contractions of the adductor pollicis muscle were studied in healthy subjects and patients with myotonic dystrophy after single and double stimuli of the ulnar nerve using a wide range of interstimulus intervals (ISI, 0.4-180 ms). In healthy subjects, the force contributed by a second stimulus was greater than the single twitch force being maximal (mean + 140%) at 12-ms ISI. In myotonic dystrophy, the force contributed by the second stimulus was (relative to a reduced twitch amplitude) increased (mean + 204%) with a maximum at 4.8-ms ISI. An abnormal increase of force was only recorded if the single twitch force was clearly reduced. The absolute refractory period of muscle contrac…
Vascular Third Nerve Compression—A Possible Cause of Episodic Vertical Diplopia?
2006
We report a 74-year-old man with a 2-year history of episodes of vertical diplopia. In the beginning, there was one episode every 2–3 months, which increased over time to an average of one episode every 2 weeks. These complaints were attributed to an MRI-documented vascular third nerve compression. Treatment with gabapentin (400 mg q.i.d.) was followed by cessation of episodic diplopia.
The autosomal recessive (Becker) form of myotonia congenita
1979
In the last two decades, two genetically distinct forms of myotonia congenita have been identified--an autosomal dominant and an autosomal recessive form. The purpose of this review is to describe the features that enable us to distinguish between these two forms in the absence of sufficient genetic data. Thus far, it can be concluded that the only probable difference between the two forms is in the fatty-acid pattern of muscle phospholipids. Clinical, histologic, ultrastructural, and electromyographic investigation may prove helpful, but they alone cannot provide a reliable means of identifying the genotype in an individual patient.