Causes of death in multiple system atrophy

Papapetropoulos, Spiridon; Tuchman, Alexander; Laufer, Daniel; Papatsoris, Athanasios; Papapetropoulos, Nektarios; Mash, Deborah C.

doi:10.1136/jnnp.2006.103929

Cited by 67 publications

(50 citation statements)

References 9 publications

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“…The α-synucleinopathy induced by chronic activation of α 1B ARs is similar to multiple system atrophy (Papp et al 1989;Zuscik et al 2000). Multiple system atrophy can lead to early death in humans by sudden cardiopulmonary arrest or pneumonia (Papapetropoulos et al 2007). In our study, there was no increased incidence of either event in CAM-α 1B AR mice.…”

Section: Discussionmentioning

confidence: 99%

Long-term α1B-adrenergic receptor activation shortens lifespan, while α1A-adrenergic receptor stimulation prolongs lifespan in association with decreased cancer incidence

Collette

Amoth

et al. 2014

AGE

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The α 1 -adrenergic receptor (α 1 AR) subtypes, α 1A AR and α 1B AR, have differential effects in the heart and central nervous system. Long-term stimulation of the α 1A AR subtype prolongs lifespan and provides cardio-and neuro-protective effects. We examined the lifespan of constitutively active mutant (CAM)-α 1B AR mice and the incidence of cancer in mice expressing the CAM form of either the α 1A AR (CAM-α 1A AR mice) or α 1B AR. CAM-α 1B AR mice have a significantly shortened lifespan when compared with wild-type (WT) animals; however, the effect was sex dependent. Female CAM-α 1B AR mice lived significantly shorter lives, while the median lifespan of male CAM-α 1B AR mice was not different when compared with that of WT animals. There was no difference in the incidence of cancer in either sex of CAM-α 1B AR mice. The incidence of cancer was significantly decreased in CAM-α 1A AR mice when compared with that in WT, and no sex-dependent effects were observed. Further study is warranted on cancer incidence after activation of each α 1 AR subtype and the effect of sex on lifespan following activation of the α 1B AR. The implications of a decrease in cancer incidence following long-term α 1A AR stimulation could lead to improved treatments for cancer.

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Section: Discussionmentioning

confidence: 99%

Long-term α1B-adrenergic receptor activation shortens lifespan, while α1A-adrenergic receptor stimulation prolongs lifespan in association with decreased cancer incidence

Collette

Amoth

et al. 2014

AGE

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“…The disease affects older individuals with an incidence in the 50-99 year age group of 3 per 100,000 [1,2]. The mean survival after diagnosis is 9 years [3,4]. MSA is defined histopathologically by the accumulation of α-synuclein protein mainly in the cytoplasm of oligodendrocytes, the myelin producing support cells of the central nervous system [5].…”

Section: Introductionmentioning

confidence: 99%

Altered lipid levels provide evidence for myelin dysfunction in multiple system atrophy

Don

Hsiao

Bleasel

et al. 2014

Acta Neuropathologica Communications

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Multiple system atrophy (MSA) is a rapidly-progressive neurodegenerative disease characterized by parkinsonism, cerebellar ataxia and autonomic failure. A pathological hallmark of MSA is the presence of α-synuclein deposits in oligodendrocytes, the myelin-producing support cells of the brain. Brain pathology and in vitro studies indicate that myelin instability may be an early event in the pathogenesis of MSA. Lipid is a major constituent (78% w/w) of myelin and has been implicated in myelin dysfunction in MSA. However, changes, if any, in lipid level/distribution in MSA brain are unknown. Here, we undertook a comprehensive analysis of MSA myelin. We quantitatively measured three groups of lipids, sphingomyelin, sulfatide and galactosylceramide, which are all important in myelin integrity and function, in affected (under the motor cortex) and unaffected (under the visual cortex) white matter regions. For all three groups of lipids, most of the species were severely decreased (40-69%) in affected but not unaffected MSA white matter. An analysis of the distribution of lipid species showed no significant shift in fatty acid chain length/content with MSA. The decrease in lipid levels was concomitant with increased α-synuclein expression. These data indicate that the absolute levels, and not distribution, of myelin lipids are altered in MSA, and provide evidence for myelin lipid dysfunction in MSA pathology. We propose that dysregulation of myelin lipids in the course of MSA pathogenesis may trigger myelin instability.

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“…Sudden death has been reported in patients with multiple system atrophy (MSA) [7][8][9]13], although the frequency of this event has not been well delineated. The mechanism underlying sudden death remains unclear; it may be explained by laryngeal obstruction due to vocal cord abductor paralysis (VCAP) [3].…”

Section: Introductionmentioning

confidence: 99%

Frequency of nocturnal sudden death in patients with multiple system atrophy

et al. 2008

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Sudden death has been reported in patients with multiple system atrophy (MSA), although the frequency of this event has not been well delineated. We investigated the frequency and potential causes of sudden death in patients with MSA. During the 5-year observation period, 10 of 45 patients with probable MSA died. The causes of death included sudden death of unknown etiology (seven patients), aspiration pneumonia (one patient), asphyxia after vomiting (one patient), and lung cancer (one patient). The mean survival time of patients with sudden death was 63.0 +/- 24.7 months (range, 39-116 months). Among seven patients who experienced sudden death, six were found to have died during sleep. Among these patients, two had been treated with tracheostomy and three with continuous positive airway pressure (CPAP) or noninvasive positive pressure ventilation (NPPV) during sleep, suggesting that these treatments do not always prevent sudden death in patients with MSA. Nocturnal sudden death should be recognized as the most common mechanism of death in patients with MSA.

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Causes of death in multiple system atrophy

Cited by 67 publications

References 9 publications

Long-term α1B-adrenergic receptor activation shortens lifespan, while α1A-adrenergic receptor stimulation prolongs lifespan in association with decreased cancer incidence

Long-term α1B-adrenergic receptor activation shortens lifespan, while α1A-adrenergic receptor stimulation prolongs lifespan in association with decreased cancer incidence

Altered lipid levels provide evidence for myelin dysfunction in multiple system atrophy

Frequency of nocturnal sudden death in patients with multiple system atrophy

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