Myotonia-like symptoms in a patient with spinal and bulbar muscular atrophy

Araki, Kunihiko; Nakanishi, Hiroyuki; Nakamura, Tomohiko; Atsuta, Naoki; Yamada, Shinichiro; Hijikata, Yasuki; Hashizume, Akira; Suzuki, Keisuke; Katsuno, Masahisa; Sobue, Gen

doi:10.1016/j.nmd.2015.08.006

Cited by 15 publications

(15 citation statements)

References 22 publications

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“…Alteration of SERCA function has been linked also to myotonic dystrophy and hypothyroid myopathy, and decreased activity/concentration of this protein is associated with selective atrophy of fast myofibers (60). Interestingly, myotonia-like symptoms have been reported also in SBMA patients (61), and SERCA1 was decreased in AR100Q mice. Notably, changes in Atp2a1 expression were detected very early, before motor dysfunction, suggesting that they may play a pathogenic role in SBMA muscle.…”

Section: Discussionmentioning

confidence: 99%

Polyglutamine-expanded androgen receptor disrupts muscle triad, calcium dynamics and the excitation-contraction coupling gene expression program

Chivet

Marchioretti

Pirazzini

et al. 2019

Preprint

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Spinal and bulbar muscular atrophy (SBMA) is caused by polyglutamine (polyQ) expansions in the androgen receptor (AR) gene. Although clinical and experimental evidence highlight a primary role for skeletal muscle in the onset, progression, and outcome of disease, the pathophysiological and molecular processes underlying SBMA muscle atrophy are poorly understood. Here we show that polyQ-expanded AR alters intrinsic muscle force generation before denervation. Reduced muscle force was associated with a switch in fiber-type composition, disrupted muscle striation, altered calcium (Ca ++ ) dynamics in response to muscle contraction, and aberrant expression of excitation-contraction coupling (ECC) machinery genes in transgenic, knock-in and inducible SBMA mice and patients. Importantly, treatment to suppress polyQ-expanded AR toxicity restored ECC gene expression back to normal. Suppression of AR activation by surgical castration elicited similar ECC gene expression changes in normal mice, suggesting that AR regulates the expression of these genes in physiological conditions. Bioinformatic analysis revealed the presence of androgen-responsive elements on several genes involved in muscle function and homeostasis, and experimental evidence showed AR-dependent regulation of expression and promoter occupancy of the most up-regulated gene from transcriptomic analysis in SBMA muscle, i.e. sarcolipin, a key ECC gene. These observations reveal an unpredicted role for AR in the regulation of expression of genes involved in muscle contraction and Ca ++ dynamics, a level of muscle function regulation that is disrupted in SBMA muscle, yet restored by pharmacologic treatment.

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Section: Discussionmentioning

confidence: 99%

Polyglutamine-expanded androgen receptor disrupts muscle triad, calcium dynamics and the excitation-contraction coupling gene expression program

Chivet

Marchioretti

Pirazzini

et al. 2019

Preprint

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“…2, 3). В литературе имеется единственное описание пациента с подобным нарушением при типичной картине генетической доказанной СБМА [14]. У японца 33 лет в течение 4 лет постепенно нарастали скованность, слабость и затруднение расслабления мышц правой руки после привычных произвольных усилий (манипуляция палочками при еде, письме, особенно при низкой температуре окружающей среды).…”

Section: Discussionunclassified

“…Поскольку все дополнительные исследования в обоих случаях не выявили данных за дополнительное генетическое заболевание, встает вопрос о связи задержки расслабления мышц с дисфункцией ионных каналов поперечно-полосатых мышц. Положительный эффект мексилетина, показанный японскими авторами, косвенно подтверждает справедливость гипотезы [14].…”

Section: Discussionunclassified

Spinal and bulbar muscular atrophy with pseudomyotonia phenomena: a clinical case report

Никитин

Григорьева

Машкович

et al. 2020

Neuromuscular Diseases

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A clinical description of a 28-year-old man with spinal and bulbar muscular atrophy diagnosed on the basis of the CAG-trinucleotide expansion in the gene coding androgen receptor is presented. He exhibited skeletal muscles and tongue fasciculations, gynecomastia, increased serum testosterone and creatine kinase levels. The peculiarities of the case were the gynecomastia under the age of 7, development of fasciculations at the age of 11 and appearance of hard muscle stiffness with delayed muscle relaxation after voluntary contraction at the age of 15, which resembled typical myotonia. Electromyography showed few signs of mild without myotonic discharge, contrasting with giant motor unit potentials and reduced recruitment. The cause of myotonia-like symptom without myotonic discharge as a feature of skeletal muscles disorder is discussed with the modern view of spinal and bulbar muscular atrophy as a multisystem genetic pathology.

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“…2 Literature searches for clinical or electrodiagnostic myotonia with JMA did not reveal any results. Araki 5 reported myotonia-like symptoms in a patient with spinal and bulbar muscular atrophy, but without electrodiagnostic evidence of myotonia. The appearance of this striking electrodiagnostic finding does not appear to exclude JMA.…”

Section: Discussionmentioning

confidence: 99%

Clinical Reasoning: A 26-year-old man with right hand and arm weakness

Elliott

Smith

2019

Neurology

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A 26-year-old infantryman developed right hand and arm weakness while deployed to Iraq. Extension of the right second digit worsened over 2 weeks, followed by difficulty extending digits 3-5 over the following weeks. He reported muscle twitching in the right upper extremity over the same period, and that his thumb would lock or cramp in an opposed position during use. He denied pain, motor, or sensory symptoms in other extremities. Nine months prior, he sustained an injury while parachuting during airborne school, resulting in a concussion, headache, and neck and back pain, but no weakness.

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Myotonia-like symptoms in a patient with spinal and bulbar muscular atrophy

Cited by 15 publications

References 22 publications

Polyglutamine-expanded androgen receptor disrupts muscle triad, calcium dynamics and the excitation-contraction coupling gene expression program

Polyglutamine-expanded androgen receptor disrupts muscle triad, calcium dynamics and the excitation-contraction coupling gene expression program

Spinal and bulbar muscular atrophy with pseudomyotonia phenomena: a clinical case report

Clinical Reasoning: A 26-year-old man with right hand and arm weakness

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