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Research paper
Autopsy confirmed multiple system atrophy cases: Mayo experience and role of autonomic function tests
  1. Valeria Iodice1,
  2. Axel Lipp2,
  3. J Eric Ahlskog3,
  4. Paola Sandroni3,
  5. Robert D Fealey3,
  6. Joseph E Parisi4,
  7. Joseph Y Matsumoto3,
  8. Eduardo E Benarroch3,
  9. Kurt Kimpinski5,
  10. Wolfgang Singer3,
  11. Tonette L Gehrking3,
  12. Jade A Gehrking3,
  13. David M Sletten3,
  14. Ann M Schmeichel3,
  15. James H Bower3,
  16. Sid Gilman6,
  17. Juan Figueroa3,
  18. Phillip A Low3
  1. 1Neurovascular and Autonomic Medicine Unit, Imperial College London, UK
  2. 2Department of Neurology, Charité–University Medizin Berlin, Berlin, Germany
  3. 3Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA
  4. 4Department of Pathology, Mayo Clinic, Rochester, Minnesota, USA
  5. 5Department of Neurosciences, London Health Sciences Centre, London, Ontario, Canada
  6. 6Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA
  1. Correspondence to Dr P A Low, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA; low{at}mayo.edu

Abstract

Background Multiple system atrophy (MSA) is a sporadic progressive neurodegenerative disorder characterised by autonomic failure, manifested as orthostatic hypotension or urogenital dysfunction, with combinations of parkinsonism that is poorly responsive to levodopa, cerebellar ataxia and corticospinal dysfunction. Published autopsy confirmed cases have provided reasonable neurological characterisation but have lacked adequate autonomic function testing.

Objectives To retrospectively evaluate if the autonomic characterisation of MSA is accurate in autopsy confirmed MSA and if consensus criteria are validated by autopsy confirmation.

Methods 29 autopsy confirmed cases of MSA evaluated at the Mayo Clinic who had undergone formalised autonomic testing, including adrenergic, sudomotor and cardiovagal functions and Thermoregulatory Sweat Test (TST), from which the Composite Autonomic Severity Score (CASS) was derived, were included in the study.

Results Patient characteristics: 17 men, 12 women; age of onset 57±8.1 years; disease duration to death 6.5±3.3 years; first symptom autonomic in 18, parkinsonism in seven and cerebellar in two. Clinical phenotype at first visit was MSA-P (predominant parkinsonism) in 18, MSA-C (predominant cerebellar involvement) in eight, pure autonomic failure in two and Parkinson's disease in one. Clinical diagnosis at last visit was MSA for 28 cases. Autonomic failure was severe: CASS was 7.2±2.3 (maximum 10). TST% was 65.6±33.9% and exceeded 30% in 82% of patients. The most common pattern was global anhidrosis. Norepinephrine was normal supine (203.6±112.7) but orthostatic increment of 33.5±23.2% was reduced. Four clinical features (rapid progression, early postural instability, poor levodopa responsiveness and symmetric involvement) were common.

Conclusion The pattern of severe and progressive generalised autonomic failure with severe adrenergic and sudomotor failure combined with the clinical phenotype is highly predictive of MSA.

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Footnotes

  • The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Neurological Disorders and Stroke or the National Institutes of Health.

  • Funding This work was supported in part by the National Institutes of Health (NS 32352, NS 44233, U54 NS065736), Mayo CTSA (UL1 RR24150) and Mayo Funds. The Autonomic Diseases Consortium is a part of the NIH Rare Diseases Clinical Research Network (RDCRN). Funding and/or programmatic support for this project has been provided by U54 NS065736 from the National Institute of Neurological Diseases and Stroke (NINDS) and the NIH Office of Rare Diseases Research (ORDR).

  • Competing interests None.

  • Ethics approval The study was approved by the institutional review board.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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