Electrodiagnosis of Myotonic Disorders

Hehir, Michael K.; Logigian, Eric L.

doi:10.1016/j.pmr.2012.08.015

Cited by 24 publications

(23 citation statements)

References 28 publications

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“…In principle, membrane lesions that limit chloride or enhance sodium conductance into the myofiber could shift the resting membrane potential towards the threshold for depolarization, with associated repetitive electrical discharges [21]. Consistent with this observation, mutations in chloride (CLCN1) and sodium (SCN4A) skeletal muscle channel genes have been incriminated in the myotonias [16]. Moreover, dysregulation of Na V 1.4, the protein product of SCN4A, leads to increased intracellular sodium and cell death in mdx mice [22], which also express CRDs [23, 24].…”

Section: Disease Pathogenesis: the Membrane Theorymentioning

confidence: 96%

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The golden retriever model of Duchenne muscular dystrophy

2017

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Duchenne muscular dystrophy (DMD) is an X-linked disease caused by mutations in the DMD gene and loss of the protein dystrophin. The absence of dystrophin leads to myofiber membrane fragility and necrosis, with eventual muscle atrophy and contractures. Affected boys typically die in their second or third decade due to either respiratory failure or cardiomyopathy. Despite extensive attempts to develop definitive therapies for DMD, the standard of care remains prednisone, which has only palliative benefits. Animal models, mainly the mdx mouse and golden retriever muscular dystrophy (GRMD) dog, have played a key role in studies of DMD pathogenesis and treatment development. Because the GRMD clinical syndrome is more severe than in mice, better aligning with the progressive course of DMD, canine studies may translate better to humans. The original founder dog for all GRMD colonies worldwide was identified in the early 1980s before the discovery of the DMD gene and dystrophin. Accordingly, analogies to DMD were initially drawn based on similar clinical features, ranging from the X-linked pattern of inheritance to overlapping histopathologic lesions. Confirmation of genetic homology between DMD and GRMD came with identification of the underlying GRMD mutation, a single nucleotide change that leads to exon skipping and an out-of-frame DMD transcript. GRMD colonies have subsequently been established to conduct pathogenetic and preclinical treatment studies. Simultaneous with the onset of GRMD treatment trials, phenotypic biomarkers were developed, allowing definitive characterization of treatment effect. Importantly, GRMD studies have not always substantiated findings from mdx mice and have sometimes identified serious treatment side effects. While the GRMD model may be more clinically relevant than the mdx mouse, usage has been limited by practical considerations related to expense and the number of dogs available. This further complicates ongoing broader concerns about the poor rate of translation of animal model preclinical studies to humans with analogous diseases. Accordingly, in performing GRMD trials, special attention must be paid to experimental design to align with the approach used in DMD clinical trials. This review provides context for the GRMD model, beginning with its original description and extending to its use in preclinical trials.

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Section: Disease Pathogenesis: the Membrane Theorymentioning

confidence: 96%

“…The occurrence of CRDs is of particular interest, given their predominance on EMG studies in canine dystrophinopathies (see below). Previously called pseudomyotonia or bizarre high-frequency discharges, CRDs are high frequency spontaneous potentials that begin and end abruptly [16, 17] (Fig. 2).…”

Section: Disease Pathogenesis: the Membrane Theorymentioning

confidence: 99%

The golden retriever model of Duchenne muscular dystrophy

2017

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“…The electromyographic changes of neuromyotonia, possibly, arise from spontaneous depolarization or ephaptic transmission along segments of a demyelinated nerve secondary to altered membrane excitability. [71112] Our patient had typical findings of neuromyotonia limited to the muscles innervated by the L5, S1 radicles along with spontaneous activity in lumbar paraspinal muscles.…”

Section: Discussionmentioning

confidence: 83%

Focal neuromyotonia as a presenting feature of lumbosacral radiculopathy

Raut

Garg

Chaudhari

et al. 2013

Ann Indian Acad Neurol

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Neuromyotonia is characterized by motor, sensory, and autonomic features along with characteristic electrophysiologic findings, resulting from hyperexcitability of the peripheral nerves. We describe the case of a 36-year-old man, who presented with the disabling symptoms suggestive of focal neuromyotonia involving both the lower limbs. His neurological examination revealed continuous rippling of both the calf muscles with normal power, reflexes, and sensory examination. Electrophysiology revealed spontaneous activity in the form of doublets, triplets, and neuromyotonic discharges along with the neurogenic motor unit potentials in bilateral L5, S1 innervated muscles. Magnetic resonance imaging lumbosacral spine revealed lumbar intervertebral disc protrusion with severe foraminal and spinal canal stenosis. Patient had good response to steroids and carbamazepine. The disabling focal neuromyotonia, occurring as a result of chronic active radiculopathy, brought the patient to medical attention. Patient responded to medical management.

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“…For example, in an inflammatory myopathy, there is increased spontaneous activity with presence of fibrillations, complex repetitive discharges and positive sharp waves . EMG can also be helpful in identifying myotonic disorders insertion of the electrode and may trigger an extended series of repetitive discharges lasting up to 30 s …”

Section: Initial Investigationsmentioning

confidence: 99%

Muscle disorders: the latest investigations

Ghaoui

Clarke

Hollingworth

et al. 2013

Internal Medicine Journal

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Patients with muscle disorders can present a diagnostic challenge to physicians because of the different ways they can present and the large number of different underlying causes. Recognition of the 'myopathic phenotype' coupled with investigations usually including electrodiagnostic and histological investigations have been essential for diagnosing the underlying cause of a myopathy. Despite these standard investigations, some patients can remain undiagnosed. New tests including more specific antibody tests for immune-mediated myopathies and the introduction of next-generation sequencing promise to revolutionise diagnostic approaches for immune and inherited myopathies, but clinical expertise remains essential to choose the most appropriate tests and interpret the results. The aim of this review is to provide an overview of the different presentations to the neuromuscular clinic and the latest investigations that can be helpful in the diagnosis of muscle disorders.

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Electrodiagnosis of Myotonic Disorders

Cited by 24 publications

References 28 publications

The golden retriever model of Duchenne muscular dystrophy

The golden retriever model of Duchenne muscular dystrophy

Focal neuromyotonia as a presenting feature of lumbosacral radiculopathy

Muscle disorders: the latest investigations

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