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Clinical Relevance of Orthostatic Hypotension in Neurodegenerative Disease

  • Behavior (HS Kirshner, Section Editor)
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Abstract

The autonomic nervous system appears to be uniquely susceptible to degeneration in disorders of α-synuclein pathology. Clinically, autonomic dysfunction in these disorders manifests as neurogenic orthostatic hypotension (nOH), a condition that results in substantial morbidity and mortality. nOH results from pathology affecting either the central autonomic pathways or peripheral autonomic nerve fibers. Determining the localization and pathophysiology of nOH is critical in effectively managing this disorder and selecting appropriate treatment options. In this review, we discuss the pathophysiology of nOH with respect to the various α-synuclein-related neurodegenerative conditions. We highlight the associated clinical features, including gait instability, rapid eye movement behavior disorder, and hyposmia. We also review the current pharmacologic treatment options for nOH. Overall, the goals of therapy are to improve symptoms and prevent syncope and falls. Non-pharmacologic interventions should be introduced first, followed by carefully selected pharmacologic therapies. Treatment decisions should be directed by an understanding of the underlying pathophysiology, as well as the comorbidities and potential contributing factors present in each individual patient.

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Acknowledgments

The authors of this paper would like to thank Miss Margot Samson for her help in compiling this manuscript.

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Authors and Affiliations

  1. Department of Neurology, Vanderbilt University Medical Center, 1161 21st Avenue South A-0118, Nashville, TN, 37232-2551, USA

    Katherine E. McDonell & Daniel O. Claassen

  2. Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA

    Cyndya A. Shibao

Authors
  1. Katherine E. McDonell
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  2. Cyndya A. Shibao
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  3. Daniel O. Claassen
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Correspondence to Katherine E. McDonell.

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Conflict of Interest

Katherine E. McDonell declares that she has no conflict of interest.

Cyndya A. Shibao receives grant support from the National Institutes of Health (K23 HL103976), PhRMA Foundation Career Development Award, and the Doris Duke Clinical Scientist Career Development Award. Dr. Shibao is also a consultant for Lundbeck Pharmaceuticals.

Daniel O. Claassen received grant support from the National Institutes of Health (K23 NS080988) and the Michael J. Fox Foundation and is a consultant for Lundbeck Pharmaceuticals. Dr. Claassen has also received honoraria for speaking and advisory board participation from Lundbeck Pharmaceuticals; this work was related to droxidopa.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

Funding

The authors did not receive any funding or compensation for the submitted manuscript. Assistance with formatting of the manuscript and figures was provided by the CHC Group, which was funded by Lundbeck, Inc. CHC did not provide any input into the content of the manuscript. The manuscript was drafted, written, and revised by the authors and represents their original work.

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McDonell, K.E., Shibao, C.A. & Claassen, D.O. Clinical Relevance of Orthostatic Hypotension in Neurodegenerative Disease. Curr Neurol Neurosci Rep 15, 78 (2015). https://doi.org/10.1007/s11910-015-0599-0

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