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Abstract

Objectives:

To determine the characteristics of adult-onset autoimmune chorea, and compare paraneoplastic and idiopathic subgroups.

Methods:

Thirty-six adults with autoimmune chorea were identified at Mayo Clinic (Rochester, MN) from 1997 to 2012. Medical record and laboratory data were recorded. Nonparaneoplastic (n = 22) and paraneoplastic cases (n = 14) were compared.

Results:

Women accounted for 21 patients (58%). Median age at symptom onset was 67 years (range 18–87 years). We estimated the incidence for Olmsted County was 1.5 per million person-years. Symptom onset was subacute in all. Chorea was focal (20 patients) or generalized (16 patients). Although chorea predominated, other neurologic disorders frequently coexisted (29 patients); abnormal eye movements were uncommon (4 patients). No patient had NMDA receptor antibody or any immunoglobulin (Ig)G yielding a detectable immunofluorescence binding pattern restricted to basal ganglia. Two had synaptic IgG antibodies novel to the context of chorea (GAD65, 1; CASPR2, 1). In the paraneoplastic group, 14 patients had evidence of cancer. Of 13 with a histopathologically confirmed neoplasm, small-cell carcinoma and adenocarcinoma were most common; 6 patients had a cancer-predictive paraneoplastic autoantibody, with CRMP-5–IgG and ANNA-1 being most common. In the idiopathic group, 19 of the 22 patients had a coexisting autoimmune disorder (most frequently systemic lupus erythematosus and antiphospholipid syndrome); autoantibodies were detected in 21 patients, most frequently lupus and phospholipid specificities (19 patients). The paraneoplastic group was older (p = 0.001), more frequently male (p = 0.006), had more frequent weight loss (p = 0.02), and frequently had peripheral neuropathy (p = 0.008).

Conclusions:

Autoimmune chorea is a rare disorder with rapid onset. Male sex, older age, severe chorea, coexisting peripheral neuropathy, and weight loss increase the likelihood of cancer.

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Supplementary Material

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Information & Authors

Information

Published In

Neurology®
Volume 80Number 12March 19, 2013
Pages: 1133-1144
PubMed: 23427325

Publication History

Received: September 1, 2012
Accepted: December 11, 2012
Published online: February 20, 2013
Published in print: March 19, 2013

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Disclosure

O. O'Toole reports no disclosures. V. Lennon is a named inventor on a patent relating to AQP4 antibodies for diagnosis of NMO and receives royalties for this technology; is a named inventor on filed patents that relate to functional AQP4/NMO-IgG assays and AQP4-IgG as a cancer marker; and receives research support from the NIH. J.E. Ahlskog and J. Matsumoto report no disclosures. S. Pittock is a named inventor on filed patents that relate to functional AQP4/NMO-IgG assays and AQP4-IgG as a cancer marker and receives research support from Alexion Pharmaceuticals, Inc., the Guthy-Jackson Charitable Foundation, and the NIH. J. Bower, R. Fealey, and D. Lachance report no disclosures. A. McKeon receives research support from the Guthy-Jackson Charitable Foundation. Go to Neurology.org for full disclosures.

Study Funding

No targeted funding reported.

Authors

Affiliations & Disclosures

Orna O'Toole, MD
From the Departments of Neurology (O.O., V.A.L., J.E.A., J.Y.M., S.J.P., J.B., R.F., D.H.L., A.M.), Laboratory Medicine and Pathology (V.A.L., S.J.P., D.H.L., A.M.), and Immunology (V.A.L.), Mayo Clinic, College of Medicine, Rochester, MN.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Vanda A. Lennon, MD, PhD
From the Departments of Neurology (O.O., V.A.L., J.E.A., J.Y.M., S.J.P., J.B., R.F., D.H.L., A.M.), Laboratory Medicine and Pathology (V.A.L., S.J.P., D.H.L., A.M.), and Immunology (V.A.L.), Mayo Clinic, College of Medicine, Rochester, MN.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
Dr. Lennon and Mayo Clinic have a financial interest in the following intellectual property:
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Guthy-Jackson Charitable Foundation
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
Dr. Lennon has a potential financial interest in the technologies listed below:
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
J. Eric Ahlskog, PhD, MD
From the Departments of Neurology (O.O., V.A.L., J.E.A., J.Y.M., S.J.P., J.B., R.F., D.H.L., A.M.), Laboratory Medicine and Pathology (V.A.L., S.J.P., D.H.L., A.M.), and Immunology (V.A.L.), Mayo Clinic, College of Medicine, Rochester, MN.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
American Parkinson's Disease Association Fred Springer Award, 2007
Funding for Travel or Speaker Honoraria:
1.
Visiting Professor, Grand Rounds or invited lectures at the following non-profit medical centers or institutions: Visiting Professor Royal University Hospital University of Saskatchewan (2007) Neuroscience Grand Rounds, Primary Care Rounds lectures Bayfront Medical Center, St. Petersburg, Florida (2008, 2009 & 2010) Visiting Professor, Dept. of Neurology Michigan State University East Lansing, Michigan (2008) Internal Medicine Grand Rounds speaker; Psychiatry Grand Rounds speaker Sanford School of Medicine The University of South Dakota Sioux Falls, SD (2008) Course Faculty, Regional course: Parkinson's disease: Sharing Wisdom Nevada Geriatric Education Center, Las Vegas NV (2008) Grand Rounds lecture, Community Education lecture St. Charles Medical Center, Bend, Oregon (2009 Course Faculty, Regional course: Parkinson's disease: Sharing Wisdom Nevada Geriatric Education Center, Reno, NV (2009) Keynote Speaker, Annual Conference of the Special Parkinson Research Interest Group of the United Kingdom, London, United Kingdom (2009) Keynote Speaker, APDA Young Onset Parkinson Conference, Dallas, Texas (2009) Keynote speaker, APDA Annual Parkinson's Disease Symposium, South Florida Chapter, Boca Raton, FL (2010) Keynote Speaker, Parkinson's Resources of Oregon, Eugene, Oregon (2010) Visiting Professor, University of Tennessee Neuroscienes Institute, Memphis, Tennessee (2010) Keynote speaker, Neuro Challenge Foundation Parkinson's Disease Symposium, Sarasota, Florida, (2010) Course Faculty, Medical College of Wisconsin Parkinson's Symposium, Milwaukee, Wisconsin (2010) Course Faculty, Lee Memorial Health System Neurology Conference, Fort Myers, Florida (2011, 2012) Course Faculty, Parkinson's and Partnerships Conference Victoria, BC, Canada; April 2012 Faculty, National Parkinson Foundation, South Dakota Conference; Sioux Falls, SD March 2012 Parkinson Society of Central and Northern Ontario Faculty Peterborough, Ontarior, Canada; October 2012 Faculty, International Symposium on early diagnosis and new therapies in Parkinson's disease. Copenhagen, Denmark; November 2012
Editorial Boards:
1.
Editorial Boards (no compensation): 1. Parkinsonism and Related Disorders, 2009 to present 2. Clinical Neuropharmacology, 1996 to present
Patents:
1.
NONE
Publishing Royalties:
1.
Royalties from 2 books which I solely authored: Authored books: 1. The Parkinson's Disease Treatment Book; Oxford University Press, 2005. 2.Parkinson's Disease Treatment Guide for Physicians; Oxford University Press, 2009. Royalties from co-edited book (with Dr. Charles Adler): Parkinson' Disease and Movement Disorders, Humana Press, 2000. Royalty from book that I co-edited: Parkinson's Disease and Movement Disorders; Adler and Ahlskog. Humana Press, 2000. Royalty from book chapter in Surgical Treatment of Parkinson's Disease and other Movement Disorders, edited by Tarsy, Vitek & Lozano; Humana Press, 2003.
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
Genetics and Molecular Biology of Parkinsonism - UDALL Center - subcontract. Funded by National Institute of Neurological Disorders and Stroke. (P50 NS 40256-R) 4-8% FTE through 2010; Molecular Epidemiology of Parkinson's Disease - subcontract. Funded by the National Institute of Health (2R01 ES-10751) 5%-15% FTE through October 2012.
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Joseph Y. Matsumoto, MD
From the Departments of Neurology (O.O., V.A.L., J.E.A., J.Y.M., S.J.P., J.B., R.F., D.H.L., A.M.), Laboratory Medicine and Pathology (V.A.L., S.J.P., D.H.L., A.M.), and Immunology (V.A.L.), Mayo Clinic, College of Medicine, Rochester, MN.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Sean J. Pittock, MD
From the Departments of Neurology (O.O., V.A.L., J.E.A., J.Y.M., S.J.P., J.B., R.F., D.H.L., A.M.), Laboratory Medicine and Pathology (V.A.L., S.J.P., D.H.L., A.M.), and Immunology (V.A.L.), Mayo Clinic, College of Medicine, Rochester, MN.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
Dr. Pittock and Mayo Clinic have a financial interest in the technology entitled
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
Dr. Pittock has received a research grant from Alexion pharmaceuticals for his investigator-initiated study entitled
Research Support, Government Entities:
1.
RO1 NS065829-01 entitled "CNS Demyelinating Autoimmunity Targeting Water Channel Complexes"
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Guthy Jackson Charitable Foundation grant for NMO research
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
James Bower, MD
From the Departments of Neurology (O.O., V.A.L., J.E.A., J.Y.M., S.J.P., J.B., R.F., D.H.L., A.M.), Laboratory Medicine and Pathology (V.A.L., S.J.P., D.H.L., A.M.), and Immunology (V.A.L.), Mayo Clinic, College of Medicine, Rochester, MN.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
1)Teva Pharmaceuticals 2)Merz Pharmaceuticals
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NIH 1R21TW008412-01 PI Measurement of the Prevalence of Neurologic Morbidity in Two African Communities 2009-2011
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Robert Fealey, MD
From the Departments of Neurology (O.O., V.A.L., J.E.A., J.Y.M., S.J.P., J.B., R.F., D.H.L., A.M.), Laboratory Medicine and Pathology (V.A.L., S.J.P., D.H.L., A.M.), and Immunology (V.A.L.), Mayo Clinic, College of Medicine, Rochester, MN.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
We perform the thermoregulatory sweat test in the laboratory I direct. We have done this since 1981 until the present time. I do not directly get reimbursement from this test.
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Daniel H. Lachance, MD
From the Departments of Neurology (O.O., V.A.L., J.E.A., J.Y.M., S.J.P., J.B., R.F., D.H.L., A.M.), Laboratory Medicine and Pathology (V.A.L., S.J.P., D.H.L., A.M.), and Immunology (V.A.L.), Mayo Clinic, College of Medicine, Rochester, MN.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
1) Not for profit; 2)CERN (collaborative Ependymoma Research Network) meeting travel expenses only
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
(1) NIH/NCI P50CA108961-06, 09/01/2011 - 08/31/2016; Co-director – Clinical Core E; (2) NIH/NCI CA139020-02, 03/01/2010-12/31/2014, Co-investigator
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Andrew McKeon, MD
From the Departments of Neurology (O.O., V.A.L., J.E.A., J.Y.M., S.J.P., J.B., R.F., D.H.L., A.M.), Laboratory Medicine and Pathology (V.A.L., S.J.P., D.H.L., A.M.), and Immunology (V.A.L.), Mayo Clinic, College of Medicine, Rochester, MN.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Guthy Jackson Charitable Foundation
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE

Notes

Correspondence to Dr. McKeon: [email protected]
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

Author Contributions

Dr. O'Toole: acquisition of data, analysis and interpretation of data, drafting the manuscript. Dr. Lennon: analysis and interpretation of data, revising the manuscript for content, contribution of vital reagents/tools. Dr. Ahlskog, Dr. Matsumoto, Dr. Pittock, Dr. Bower, Dr. Fealey, Dr. Lachance: acquisition of data, revising the manuscript for content. Dr. McKeon: study concept and design, acquisition of data, analysis and interpretation of data, statistical analysis, drafting/revising the manuscript for content, study supervision.

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  6. Paraneoplastic Neurologic Disorders, Current Neurology and Neuroscience Reports, 23, 3, (67-82), (2023).https://doi.org/10.1007/s11910-023-01250-w
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