Pure Autonomic Failure: Diagnosis, Differential Diagnosis, and Natural History

Chapter
Part of the Contemporary Endocrinology book series (COE)

Abstract

Pure autonomic failure is an uncommon, idiopathic neurodegenerative disorder with primarily peripheral autonomic manifestations. The onset and progression of symptoms are gradual, and the presenting feature is characteristically orthostatic hypotension. Other commonly reported features of autonomic failure include constipation, bladder dysfunction, erectile dysfunction, and sweating abnormalities. The disorder is one of the alpha-synucleinopathies, a heterogenous group of disorders characterized by abnormal accumulation of the presynaptic protein, alpha-synuclein, in the central and/or peripheral nervous system. Although the initial presentation may be one of isolated peripheral autonomic impairment, over a period of time, some patients may develop motor and cognitive deficits that indicate central neuronal degeneration, and a phenotype consistent with one of the central alpha-synucleinopathies, Parkinson’s disease (PD), dementia with Lewy bodies, or multiple system atrophy.

Keywords

Pure autonomic failure Alpha-synuclein Parkinson’s disease Dementia with Lewy bodies Multiple system atrophy Orthostatic hypotension Supine hypertension Autonomic nervous system Parasympathetic nervous system Sympathetic nervous system Autonomic failure 

References

  1. 1.
    Bradbury S, Eggleston C. Postural hypotension: report of 3 cases. Am Heart J. 1925;1:73–86.CrossRefGoogle Scholar
  2. 2.
    Goodall MC, Harlan WR Jr, Alton H. Decreased noradrenaline (norepinephrine) synthesis in neurogenic orthostatic hypotension. Circulation. 1968;38:592–603.CrossRefGoogle Scholar
  3. 3.
    Bannister R, Crowe R, Eames R, Burnstock G. Adrenergic innervation in autonomic failure. Neurology. 1981;31:1501–6.CrossRefGoogle Scholar
  4. 4.
    Johnson RH, Lee Gde J, Oppenheimer DR, Spalding JM. Autonomic failure with orthostatic hypotension due to intermediolateral column degeneration. A report of two cases with autopsies. Q J Med. 1966;35(138):276–92.PubMedGoogle Scholar
  5. 5.
    Kaufmann H, Norcliffe-Kaufmann L, Palma JA, Biaggioni I, Low PA, Singer W, et al. Natural history of pure autonomic failure: a United States prospective cohort. Ann Neurol. 2017;81(2):287–97.CrossRefGoogle Scholar
  6. 6.
    Singer W, Berini SE, Sandroni P, Fealey RD, Coon EA, Suarez MD, et al. Pure autonomic failure: predictors of conversion to clinical CNS involvement. Neurology. 2017;88(12):1129–36.CrossRefGoogle Scholar
  7. 7.
    Hague K, Lento P, Morgello S, Caro S, Kaufmann H. The distribution of Lewy bodies in pure autonomic failure: autopsy findings and review of the literature. Acta Neuropathol(Berl). 1997;94(2):192–6.CrossRefGoogle Scholar
  8. 8.
    Arai K, Kato N, Kashiwado K, Hattori T. Pure autonomic failure in association with human alpha-synucleinopathy. Neurosci Lett. 2000;296(2–3):171–3.CrossRefGoogle Scholar
  9. 9.
    Kaufmann H, Hague K, Perl D. Accumulation of alpha-synuclein in autonomic nerves in pure autonomic failure. Neurology. 2001;56(7):980–1.CrossRefGoogle Scholar
  10. 10.
    Hague K, Lento P, Morgello S, Caro S, Kaufmann H. The distribution of Lewy bodies in pure autonomic failure: autopsy findings and review of the literature. [review] [16 refs]. Acta Neuropathol(Berl). 1997;94(2):192–6.CrossRefGoogle Scholar
  11. 11.
    Fanciulli A, Stefanova N, Scherfler C, Moser P, Seppi K, Gizewski ER, et al. Very late-onset pure autonomic failure. Mov Disord Off J Mov Disord Soc. 2017;32(7):1106–8.CrossRefGoogle Scholar
  12. 12.
    Gibbons CH, Freeman R. Orthostatic dyspnea: a neglected symptom of orthostatic hypotension. Clin Auton Res. 2005;15(1):40–4.CrossRefGoogle Scholar
  13. 13.
    Centi J, Freeman R, Gibbons CH, Neargarder S, Canova AO, Cronin-Golomb A. Effects of orthostatic hypotension on cognition in Parkinson disease. Neurology. 2017;88(1):17–24.CrossRefGoogle Scholar
  14. 14.
    Robertson D, Kincaid DW, Haile V, Robertson RM. The head and neck discomfort of autonomic failure: an unrecognized aetiology of headache. Clin Auton Res. 1994;4(3):99–103.CrossRefGoogle Scholar
  15. 15.
    Garland EM, Gamboa A, Okamoto L, Raj SR, Black BK, Davis TL, et al. Renal impairment of pure autonomic failure. Hypertension. 2009;54(5):1057–61.CrossRefGoogle Scholar
  16. 16.
    Arnold AC, Okamoto LE, Gamboa A, Black BK, Raj SR, Elijovich F, et al. Mineralocorticoid receptor activation contributes to the supine hypertension of autonomic failure. Hypertension. 2016;67(2):424–9.PubMedGoogle Scholar
  17. 17.
    Arnold AC, Okamoto LE, Gamboa A, Shibao C, Raj SR, Robertson D, et al. Angiotensin II, independent of plasma renin activity, contributes to the hypertension of autonomic failure. Hypertension. 2013;61(3):701–6.CrossRefGoogle Scholar
  18. 18.
    Shannon JR, Jordan J, Diedrich A, Pohar B, Black BK, Robertson D, et al. Sympathetically mediated hypertension in autonomic failure. Circulation. 2000;101(23):2710–5.CrossRefGoogle Scholar
  19. 19.
    Mann S, Altman DG, Raftery EB, Bannister R. Circadian variation of blood pressure in autonomic failure. Circulation. 1983;68:477–83.CrossRefGoogle Scholar
  20. 20.
    Boeve BF. Idiopathic REM sleep behaviour disorder in the development of Parkinson's disease. Lancet Neurol. 2013;12(5):469–82.CrossRefGoogle Scholar
  21. 21.
    Boeve BF, Silber MH, Saper CB, Ferman TJ, Dickson DW, Parisi JE, et al. Pathophysiology of REM sleep behaviour disorder and relevance to neurodegenerative disease. Brain. 2007;130(Pt 11):2770–88.CrossRefGoogle Scholar
  22. 22.
    Miglis MG, Muppidi S, During E, Jaradeh S. A case series of REM sleep behavior disorder in pure autonomic failure. Clin Auton Res Off J Clin Auton Res Soc. 2017;27(1):41–4.CrossRefGoogle Scholar
  23. 23.
    Plazzi G, Cortelli P, Montagna P, De Monte A, Corsini R, Contin M, et al. REM sleep behaviour disorder differentiates pure autonomic failure from multiple system atrophy with autonomic failure. J Neurol Neurosurg Psychiatry. 1998;64(5):683–5.CrossRefGoogle Scholar
  24. 24.
    Braak H, Ghebremedhin E, Rub U, Bratzke H, Del Tredici K. Stages in the development of Parkinson's disease-related pathology. Cell Tissue Res. 2004;318(1):121–34.CrossRefGoogle Scholar
  25. 25.
    Lee PH, Yeo SH, Kim HJ, Youm HY. Correlation between cardiac 123I-MIBG and odor identification in patients with Parkinson's disease and multiple system atrophy. Mov Disord Off J Mov Disord Soc. 2006;21(11):1975–7.CrossRefGoogle Scholar
  26. 26.
    Silveira-Moriyama L, Mathias C, Mason L. Best C, Quinn NP, Lees AJ. Hyposmia in pure autonomic failure. Neurology. 2009;72(19):1677–81.CrossRefGoogle Scholar
  27. 27.
    Goldstein DS, Sewell L. Olfactory dysfunction in pure autonomic failure: implications for the pathogenesis of Lewy body diseases. Parkinsonism Relat Disord. 2009;15(7):516–20.CrossRefGoogle Scholar
  28. 28.
    Goldstein DS, Polinsky RJ, Garty M, Robertson D, Brown RT, Biaggioni I, et al. Patterns of plasma levels of catechols in neurogenic orthostatic hypotension. Ann Neurol. 1989;26:558–63.CrossRefGoogle Scholar
  29. 29.
    Goldstein DS, Sharabi Y. Neurogenic orthostatic hypotension: a pathophysiological approach. Circulation. 2009;119(1):139–46.CrossRefGoogle Scholar
  30. 30.
    Goldstein DS, Holmes C, Kopin IJ, Sharabi Y. Intra-neuronal vesicular uptake of catecholamines is decreased in patients with Lewy body diseases. J Clin Invest. 2011;121(8):3320–30.CrossRefGoogle Scholar
  31. 31.
    Goldstein DS, Eisenhofer G, Kopin IJ. Sources and significance of plasma levels of catechols and their metabolites in humans. J Pharmacol Exp Ther. 2003;305(3):800–11.CrossRefGoogle Scholar
  32. 32.
    Goldstein DS, Holmes C, Sharabi Y, Brentzel S, Eisenhofer G. Plasma levels of catechols and metanephrines in neurogenic orthostatic hypotension. Neurology. 2003;60(8):1327–32.CrossRefGoogle Scholar
  33. 33.
    Shishido T, Ikemura M, Obi T, Yamazaki K, Terada T, Sugiura A, et al. Alpha-synuclein accumulation in skin nerve fibers revealed by skin biopsy in pure autonomic failure. Neurology. 2010;74(7):608–10.CrossRefGoogle Scholar
  34. 34.
    Donadio V, Incensi A, Piccinini C, Cortelli P, Giannoccaro MP, Baruzzi A, et al. Skin nerve misfolded alpha-synuclein in pure autonomic failure and Parkinson disease. Ann Neurol. 2016;79(2):306–16.CrossRefGoogle Scholar
  35. 35.
    Donadio V, Incensi A, Cortelli P, Giannoccaro MP, Jaber MA, Baruzzi A, et al. Skin sympathetic fiber alpha-synuclein deposits: a potential biomarker for pure autonomic failure. Neurology. 2013;80(8):725–32.CrossRefGoogle Scholar
  36. 36.
    Freeman R. Clinical practice. Neurogenic orthostatic hypotension. N Engl J Med. 2008;358(6):615–24.CrossRefGoogle Scholar
  37. 37.
    Gibbons CH, Schmidt P, Biaggioni I, Frazier-Mills C, Freeman R, Isaacson S, et al. The recommendations of a consensus panel for the screening, diagnosis and treatment of neurogenic orthostatic hypotension and associated supine hypertension. J Neurol. 2017;264:1567.CrossRefGoogle Scholar
  38. 38.
    Omboni S, Smit AA, van Lieshout JJ, Settels JJ, Langewouters GJ, Wieling W. Mechanisms underlying the impairment in orthostatic tolerance after nocturnal recumbency in patients with autonomic failure. Clin Sci(Lond). 2001;101(6):609–18.CrossRefGoogle Scholar
  39. 39.
    Smit AA, Wieling W, Fujimura J, Denz JC, Opfer-Gehrking TL, Akarriou M, et al. Use of lower abdominal compression to combat orthostatic hypotension in patients with autonomic dysfunction. Clin Auton Res. 2004;14(3):167–75.CrossRefGoogle Scholar
  40. 40.
    Wright RA, Kaufmann HC, Perera R, Opfer-Gehrking TL, McElligott MA, Sheng KN, et al. A double-blind, dose response study of midodrine in neurogenic orthostatic hypotension. Neurology. 1998;51(1):120–4.CrossRefGoogle Scholar
  41. 41.
    Low PA, Gilden JL, Freeman R, Sheng KN, McElligott MA. Efficacy of midodrine vs placebo in neurogenic orthostatic hypotension. A randomized, doubleblind multicenter study. Midodrine study group. JAMA. 1997;277(13):1046–51.CrossRefGoogle Scholar
  42. 42.
    Biaggioni I, Freeman R, Mathias CJ, Low P, Hewitt LA, Kaufmann H, et al. Randomized withdrawal study of patients with symptomatic neurogenic orthostatic hypotension responsive to Droxidopa. Hypertension. 2015;65(1):101–7.CrossRefGoogle Scholar
  43. 43.
    Kaufmann H, Freeman R, Biaggioni I, Low P, Pedder S, Hewitt LA, et al. Droxidopa for neurogenic orthostatic hypotension: a randomized, placebo-controlled, phase 3 trial. Neurology. 2014;83(4):328–35.CrossRefGoogle Scholar
  44. 44.
    Singer W, Sandroni P, Opfer-Gehrking TL, Suarez GA, Klein CM, Hines S, et al. Pyridostigmine treatment trial in neurogenic orthostatic hypotension. Arch Neurol. 2006;63(4):513–8.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Lotus Spine and PainSan AntonioUSA
  2. 2.Autonomic and Peripheral Nerve Laboratory, Department of Neurology, Beth Israel Deaconess Medical CenterBostonUSA

Personalised recommendations