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Dear Sirs,
We read with great interest the paper “Early presentation of urinary retention in multiple system atrophy: can the disease begin in the sacral spinal cord?” [1]
The paper highlights the presentation of six patients with predominant urinary retention followed by development of multiple system atrophy (MSA) 1–7 years later.
A prion-like spread of misfolded endogenous alpha-synuclein through the central nervous system has been suggested for MSA as well as other alpha-synucleinopathies [2, 3]. However, none of the studies endeavoring to demonstrate alpha-synuclein spread have provided a clear conclusion [4]. The study by Panicker et al. points towards the pathology initiating in the sacral spinal cord. That this subset went on to develop the classical motor symptoms that met the diagnostic criteria for MSA may serve as indirect clinical evidence in favor of the spread of alpha-synuclein pathology.
Another possibility is that this series represent a subset of patients with pure autonomic failure with urinary dysfunction instead of cardiovascular dysautonomia who later phenoconverted into MSA? Did these patients demonstrate any other features of autonomic dysfunction other than genito-urinary autonomic dysfunction involvement? Three of the six patients had orthostatic hypotension. However, detailed cardiovascular autonomic function tests would have helped to assess the extent of autonomic dysfunction, further characterizing this phenotype.
We congratulate the authors on these preliminary significant observations. However, larger prospective studies of this patient subset will enable an answer to the above questions.
References
Panicker JN, Simeoni S, Miki Y, Batla A, Iodice V, Holton JL et al (2019) Early presentation of urinary retention in multiple system atrophy: can the disease begin in the sacral spinal cord? J Neurol. https://doi.org/10.1007/s00415-019-09597-2
Watts JC, Giles K, Oehler A, Middleton L, Dexter DT, Gentleman SM et al (2013) Transmission of multiple system atrophy prions to transgenic mice. Proc Natl Acad Sci USA 110(48):19555–19560. https://doi.org/10.1073/pnas.1318268110
Dhillon J-KS, Trejo-Lopez JA, Riffe C, Levites Y, Sacino AN, Borchelt DR et al (2019) Comparative analyses of the in vivo induction and transmission of α-synuclein pathology in transgenic mice by MSA brain lysate and recombinant α-synuclein fibrils. Acta Neuropathol Commun 7(1):80. https://doi.org/10.1186/s40478-019-0733-3
Wenning G, Trojanowski JQ, Kaufmann H, Wisniewski T, Rocca WA, Low PA (2018) Is multiple system atrophy an infectious disease? Ann Neurol 83(1):10–12. https://doi.org/10.1002/ana.25132
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Garg, D., Agarwal, A. Comment on “Early presentation of urinary retention in multiple system atrophy: can the disease begin in the sacral spinal cord?”. J Neurol 267, 665 (2020). https://doi.org/10.1007/s00415-019-09659-5
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DOI: https://doi.org/10.1007/s00415-019-09659-5