Conjugal multiple system atrophy: Chance, shared risk factors, or evidence of transmissibility?

Highlights

• We report conjugal MSA where both husband and wife developed MSA-parkinsonism.

• Assuming an age-specific point prevalence of MSA and independence of the two events, conjugal MSA may occur by chance.

• Exposure to shared risk factors may contribute to MSA in spousal pairs rather than offer evidence for transmissibility.

Abstract

Objective

To describe conjugal multiple system atrophy (MSA) in a couple married for 44 years, and to report environmental risk factors possibly contributing to the occurrence.

Methods

Case description of conjugal MSA with report of shared environmental risk factors and retrospective review of consecutively diagnosed MSA patients between 1998 and 2012 with autonomic reflex screen at Mayo Clinic, Rochester (clinical series). Probability calculation was based on the age-specific point prevalence of MSA.

Results

A husband and wife both developed MSA symptoms at age 63. The husband's onset was of imbalance, followed by falls and genitourinary failure; parkinsonism and antecollis was evident on examination. Autonomic testing showed widespread autonomic failure. The patient died 2.25 years after onset. The wife initially developed urinary symptoms progressing to incontinence. Parkinsonism, dysphonia, and falls began within 1 year. Autonomic testing revealed severe autonomic failure. Interview with the surviving wife and son revealed substantial chemical exposure, in particular pesticides. In our clinical series, there were no other cases of conjugal MSA. Assuming an age-specific point prevalence of MSA based on population studies and independence of the two events, the probability of both individuals developing MSA by chance is 6.08 e−9.

Conclusion

Based on the population point prevalence of MSA, conjugal MSA is rare but possible. We conclude that this case of conjugal MSA likely occurred by chance; however, exposure to shared risk factors (pesticides) may be contributory. Because this is the first reported case of conjugal MSA, to our best knowledge, evidence for transmissibility between spouses is lacking.

Introduction

Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by autonomic failure with predominantly parkinsonism (MSA-P) or cerebellar ataxia (MSA-C) [1]. Neuropathologically, MSA is a synucleinopathy characterized by α-synuclein aggregates as glial cytoplasmic inclusions [2,3]. Evidence in cell culture of self-templating propagation and animal models of transmissibility has led to the hypothesis that MSA may be a prion disease [4,5]. Transmissibility is an accepted feature of prion disease which has implications for the possibility of transmission through sexual or close personal contact [6,7]. Parkinson's disease in one spouse and MSA in the other has been reported; however, to the best of our knowledge, there are no reported cases of conjugal MSA [8]. Most reports of conjugal parkinsonism conclude, based on prevalence, that the association may be explained by chance or is related to shared environmental risk factors [9,[10], [11], [12], [13]]. In Parkinson's disease, evidence that pesticide exposure increases disease risk is substantial, but the role of individual compounds remains uncertain [14]. In MSA, environmental toxins and occupational exposures have been associated with increased risk of disease [15,16], although the role of pesticides is less certain [17]. We report the first description of conjugal MSA, determine the probability of both individuals developing disease by chance, and report on occupational exposures that may have contributed to the occurrence.