Brugada syndrome in spinal and bulbar muscular atrophy

Araki, Atsuko; Katsuno, Masahisa; Suzuki, Keisuke; Banno, Haruhiko; Suga, Noriaki; Hashizume, Akira; Mano, Tomoo; Hijikata, Yasuki; Nakatsuji, Hideaki; Watanabe, Haruo; Yamamoto, Masahiko; Makiyama, Takeru; Ohno, Seiko; Fukuyama, Megumi; Morimoto, S; Horie, Minoru; Sobue, Gen

doi:10.1212/wnl.0000000000000434

Cited by 45 publications

(50 citation statements)

References 43 publications

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“…Chloride channel dysfunction, a main cause of myotonia, is also reported in mouse models of SBMA [20,21]. Given the nuclear accumulation of the mutant AR proteins and decreased expression levels of the alpha subunit of the type V sodium channel subunit in the myocardium of patients with SBMA [22], the myotonia-like symptoms may reflect a similar muscular pathology in our patient.…”

Section: Discussionsupporting

confidence: 69%

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

Araki

Nakanishi

Nakamura

et al. 2015

Neuromuscular Disorders

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Section: Discussionsupporting

confidence: 69%

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

Araki

Nakanishi

Nakamura

et al. 2015

Neuromuscular Disorders

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“…A recent study reported a high prevalence (11.8%) of Brugada-like ECG in a Japanese population with SBMA, ascribed to a downregulation of the SCN5A gene leading to sodium current reduction in the myocardium 16. Of note, two patients had symptomatic Brugada syndrome and died suddenly during follow-up.…”

Section: Discussionmentioning

confidence: 95%

“…Elevated serum creatine kinase (CK), higher than expected for a purely neurogenic disease, and myogenic changes on muscle biopsy indicate an underlying myopathy 1314 Even if overt cardiomyopathy has not been recognised in SBMA,15 an increased incidence of Brugada-type ECG changes has been recently reported in a large Japanese population with SBMA 16…”

Section: Introductionmentioning

confidence: 99%

Non-neural phenotype of spinal and bulbar muscular atrophy: results from a large cohort of Italian patients

Querin

Bertolin

et al. 2015

J Neurol Neurosurg Psychiatry

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ObjectiveTo carry out a deep characterisation of the main androgen-responsive tissues involved in spinal and bulbar muscular atrophy (SBMA).Methods73 consecutive Italian patients underwent a full clinical protocol including biochemical and hormonal analyses, genitourinary examination, bone metabolism and densitometry, cardiological evaluation and muscle pathology.ResultsCreatine kinase levels were slightly to markedly elevated in almost all cases (68 of the 73; 94%). 30 (41%) patients had fasting glucose above the reference limit, and many patients had total cholesterol (40; 54.7%), low-density lipoproteins cholesterol (29; 39.7%) and triglyceride (35; 48%) levels above the recommended values. Although testosterone, luteinising hormone and follicle-stimulating hormone values were generally normal, in one-third of cases we calculated an increased Androgen Sensitivity Index reflecting the presence of androgen resistance in these patients. According to the International Prostate Symptom Score (IPSS), 7/70 (10%) patients reported severe lower urinal tract symptoms (IPSS score >19), and 21/73 (30%) patients were moderately symptomatic (IPSS score from 8 to 19). In addition, 3 patients were carriers of an indwelling bladder catheter. Videourodynamic evaluation indicated that 4 of the 7 patients reporting severe urinary symptoms had an overt prostate-unrelated bladder outlet obstruction. Dual-energy X-ray absorptiometry scan data were consistent with low bone mass in 25/61 (41%) patients. Low bone mass was more frequent at the femoral than at the lumbar level. Skeletal muscle biopsy was carried out in 20 patients and myogenic changes in addition to the neurogenic atrophy were mostly observed.ConclusionsOur study provides evidence of a wide non-neural clinical phenotype in SBMA, suggesting the need for comprehensive multidisciplinary protocols for these patients.

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“…The pathophysiology of Brugada syndrome in the context of SBMA has not been completely explained but intranuclear inclusions of mutated AR have been demonstrated in myocardial cells [31].…”

Section: Clinical Featuresmentioning

confidence: 99%

Kennedy disease (X-linked recessive bulbospinal neuronopathy): A comprehensive review from pathophysiology to therapy

2017

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Acknowledgments: the authors thank AFM-Téléthon, Téléthon Biobank, Institut pour la Recherche sur la Moelle épinière et l'Encéphale (IRME), Association pour la Recherche sur la SLA (ARSla) and the University of Padova for their research support.Kennedy disease (X-Linked recessive Bulbospinal Neuronopathy): a comprehensive review from pathophysiology to therapy. AbstractKennedy's disease, also known as spinal and bulbar muscular atrophy (SBMA), is a rare, adult-onset, Xlinked recessive neuromuscular disease. It is caused by expansion of a CAG repeat sequence in exon 1 of the androgen-receptor (AR) gene, encoding a poly-glutamine (polyQ) tract. Poly-Q-expanded AR accumulates in nuclei and initiates degeneration and loss of motor neurons and dorsal root ganglia. The disease has been retained to be a pure lower motor neuron disease for a long time, but recently the presence of important hyper-Creatine-Kinase-emia and of myopathic alterations on muscle biopsy has suggested the presence of a primary myopathy underlying a wide proportion of clinical manifestations. The disease, that affects male adults, is characterized by muscle weakness and atrophy localized proximally in the limbs and by bulbar involvement. Sensory disturbances are associated to the motor phenotype but may be subclinical. The most frequent systemic symptom is gynecomastia related to androgen insensitivity, but other abnormalities, such as heart rhythm and urinary disturbances, have also been reported. The course of the disease is slowly progressive with normal life expectancy. The diagnosis of SBMA is based on genetic testing, with 38 CAG repeats retained to be pathogenic. Even though several therapeutic attempts have been made in mouse models, no effective disease modifying therapy is available but symptomatic therapy is beneficial for the management of weakness, fatigability and bulbar symptoms.

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Brugada syndrome in spinal and bulbar muscular atrophy

Abstract: Subjects with SBMA often show Brugada-type ECG. The accumulation of the pathogenic androgen receptor may have a role in the myocardial involvement in SBMA.

Cited by 45 publications

References 43 publications

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

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

Non-neural phenotype of spinal and bulbar muscular atrophy: results from a large cohort of Italian patients

Kennedy disease (X-linked recessive bulbospinal neuronopathy): A comprehensive review from pathophysiology to therapy

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