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Clinical presentation and autonomic profile in Ross syndrome

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Abstract

Background

Ross syndrome is a rare disorder characterized by tonic pupils, hyporeflexia, and segmental anhidrosis. We sought to characterize the clinical presentation, associated autoimmune disorders, and autonomic profile in patients with Ross syndrome to further elucidate its pathophysiology.

Methods

We performed a retrospective chart review of all patients who underwent a thermoregulatory sweat test (TST) between 1998 and 2020 and had confirmation of the diagnosis of Ross syndrome by an autonomic disorders specialist. Standardized autonomic reflex testing was reviewed when available.

Results

Twenty-six patients with Ross syndrome were identified. The most common initial reported manifestation was an abnormal segmental sweating response in 16 patients (described as hyperhidrosis in 12 patients and anhidrosis in 4 patients) while a tonic pupil was the initial manifestation in 10 patients. Other commonly reported symptoms included fatigue, chronic cough, and increased urinary frequency. An associated autoimmune disorder was identified in one patient. Positive autoantibodies were found in a minority of patients often with unclear clinical significance. Distributions of anhidrosis encountered were segmental (n = 15), widespread (n = 7), and global (n = 4). Well-circumscribed small areas of preserved sweating within areas of anhidrosis were observed in the majority of patients (88.5%). Anhidrosis progressed slowly over time and sudomotor dysfunction was predominantly (post)ganglionic. Cardiovagal and adrenergic functions were preserved in most patients.

Conclusions

The pattern of autonomic dysfunction in Ross syndrome is suggestive of a limited autonomic ganglioneuropathy. Sudomotor impairment is prominent and should be the focus of symptomatic management; however, clinicians should be aware of symptoms beyond the classic triad.

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Funding

Supported by NIH (P01NS44233, U54NS065736, K23NS075141, R01 FD004789, R01 NS092625), Cure MSA Foundation, and CTSA Grant Number UL1 TR002377 Dominium Foundation Career Development Award in Neurodegenerative Disease Research in memory of Jack W. Safar from the National Center for Advancing Translational Science (NCATS).

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Authors and Affiliations

  1. Department of Neurology, Mayo Clinic, 200 1st Street SW, Rochester, MN, 55905, USA

    Guillaume Lamotte, Paola Sandroni, Jeremy K. Cutsforth-Gregory, Sarah E. Berini, Eduardo E. Benarroch, Kamal Shouman, Michelle L. Mauermann, Jennifer Anderson, Phillip A. Low, Wolfgang Singer & Elizabeth A. Coon

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  1. Guillaume Lamotte
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  2. Paola Sandroni
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  3. Jeremy K. Cutsforth-Gregory
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  4. Sarah E. Berini
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  5. Eduardo E. Benarroch
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  6. Kamal Shouman
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  7. Michelle L. Mauermann
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  9. Phillip A. Low
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  10. Wolfgang Singer
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  11. Elizabeth A. Coon
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Correspondence to Guillaume Lamotte.

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Lamotte, G., Sandroni, P., Cutsforth-Gregory, J.K. et al. Clinical presentation and autonomic profile in Ross syndrome. J Neurol 268, 3852–3860 (2021). https://doi.org/10.1007/s00415-021-10531-8

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  • DOI: https://doi.org/10.1007/s00415-021-10531-8

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