Skip to main content
Advertisement
  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Education
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Online Sections
    • Neurology Video Journal Club
    • Diversity, Equity, & Inclusion (DEI)
    • Neurology: Clinical Practice Accelerator
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Neurology: Neuroimmunology & Neuroinflammation COVID-19 Article Hub
    • Null Hypothesis
    • Patient Pages
    • Topics A-Z
    • Translations
    • UDDA Revision Series
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit Manuscript
    • Author Center

Advanced Search

Main menu

  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Education
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Online Sections
    • Neurology Video Journal Club
    • Diversity, Equity, & Inclusion (DEI)
    • Neurology: Clinical Practice Accelerator
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Neurology: Neuroimmunology & Neuroinflammation COVID-19 Article Hub
    • Null Hypothesis
    • Patient Pages
    • Topics A-Z
    • Translations
    • UDDA Revision Series
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit Manuscript
    • Author Center
  • Home
  • Articles
  • Issues
  • COVID-19 Article Hub
  • Infographics & Video Summaries

User menu

  • My Alerts
  • Log in

Search

  • Advanced search
Neurology Neuroimmunology & Neuroinflammation
Home
A peer-reviewed clinical and translational neurology open access journal
  • My Alerts
  • Log in
Site Logo
  • Home
  • Articles
  • Issues
  • COVID-19 Article Hub
  • Infographics & Video Summaries

Share

March 2017; 4 (2) Clinical/Scientific NotesOpen Access

Negative commercial screening test for paraneoplastic antibodies in a case of opsoclonus

Nicolas Vandenbussche, Catherine Cassiman, Maarten Schrooten, Benjamin Gille, Xavier Bossuyt, Thierry Vincent, Philip Van Damme, Koen Poesen
First published February 3, 2017, DOI: https://doi.org/10.1212/NXI.0000000000000329
Nicolas Vandenbussche
From the Department of Neurology (N.V., M.S., P.V.D.), Department of Ophthalmology (C.C.), and Laboratory Medicine (X.B., K.P.), University Hospital Leuven; Department of Microbiology and Immunology (X.B.), Experimental Laboratory Immunology, Leuven, Belgium; Department of Immunology (T.V.), St Eloi Hospital, Montpellier University, France; Department of Neurosciences (P.V.D.), Laboratory for Neurobiology; Vesalius Research Center (P.V.D.), Flemish Institute for Biotechnology (VIB); and Department of Neurosciences (B.G., K.P.), Laboratory for Molecular Neurobiomarker Research, Leuven, Belgium.
MD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Catherine Cassiman
From the Department of Neurology (N.V., M.S., P.V.D.), Department of Ophthalmology (C.C.), and Laboratory Medicine (X.B., K.P.), University Hospital Leuven; Department of Microbiology and Immunology (X.B.), Experimental Laboratory Immunology, Leuven, Belgium; Department of Immunology (T.V.), St Eloi Hospital, Montpellier University, France; Department of Neurosciences (P.V.D.), Laboratory for Neurobiology; Vesalius Research Center (P.V.D.), Flemish Institute for Biotechnology (VIB); and Department of Neurosciences (B.G., K.P.), Laboratory for Molecular Neurobiomarker Research, Leuven, Belgium.
MD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Maarten Schrooten
From the Department of Neurology (N.V., M.S., P.V.D.), Department of Ophthalmology (C.C.), and Laboratory Medicine (X.B., K.P.), University Hospital Leuven; Department of Microbiology and Immunology (X.B.), Experimental Laboratory Immunology, Leuven, Belgium; Department of Immunology (T.V.), St Eloi Hospital, Montpellier University, France; Department of Neurosciences (P.V.D.), Laboratory for Neurobiology; Vesalius Research Center (P.V.D.), Flemish Institute for Biotechnology (VIB); and Department of Neurosciences (B.G., K.P.), Laboratory for Molecular Neurobiomarker Research, Leuven, Belgium.
MD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Benjamin Gille
From the Department of Neurology (N.V., M.S., P.V.D.), Department of Ophthalmology (C.C.), and Laboratory Medicine (X.B., K.P.), University Hospital Leuven; Department of Microbiology and Immunology (X.B.), Experimental Laboratory Immunology, Leuven, Belgium; Department of Immunology (T.V.), St Eloi Hospital, Montpellier University, France; Department of Neurosciences (P.V.D.), Laboratory for Neurobiology; Vesalius Research Center (P.V.D.), Flemish Institute for Biotechnology (VIB); and Department of Neurosciences (B.G., K.P.), Laboratory for Molecular Neurobiomarker Research, Leuven, Belgium.
Msc
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xavier Bossuyt
From the Department of Neurology (N.V., M.S., P.V.D.), Department of Ophthalmology (C.C.), and Laboratory Medicine (X.B., K.P.), University Hospital Leuven; Department of Microbiology and Immunology (X.B.), Experimental Laboratory Immunology, Leuven, Belgium; Department of Immunology (T.V.), St Eloi Hospital, Montpellier University, France; Department of Neurosciences (P.V.D.), Laboratory for Neurobiology; Vesalius Research Center (P.V.D.), Flemish Institute for Biotechnology (VIB); and Department of Neurosciences (B.G., K.P.), Laboratory for Molecular Neurobiomarker Research, Leuven, Belgium.
MD, PhD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thierry Vincent
From the Department of Neurology (N.V., M.S., P.V.D.), Department of Ophthalmology (C.C.), and Laboratory Medicine (X.B., K.P.), University Hospital Leuven; Department of Microbiology and Immunology (X.B.), Experimental Laboratory Immunology, Leuven, Belgium; Department of Immunology (T.V.), St Eloi Hospital, Montpellier University, France; Department of Neurosciences (P.V.D.), Laboratory for Neurobiology; Vesalius Research Center (P.V.D.), Flemish Institute for Biotechnology (VIB); and Department of Neurosciences (B.G., K.P.), Laboratory for Molecular Neurobiomarker Research, Leuven, Belgium.
MD, PhD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Philip Van Damme
From the Department of Neurology (N.V., M.S., P.V.D.), Department of Ophthalmology (C.C.), and Laboratory Medicine (X.B., K.P.), University Hospital Leuven; Department of Microbiology and Immunology (X.B.), Experimental Laboratory Immunology, Leuven, Belgium; Department of Immunology (T.V.), St Eloi Hospital, Montpellier University, France; Department of Neurosciences (P.V.D.), Laboratory for Neurobiology; Vesalius Research Center (P.V.D.), Flemish Institute for Biotechnology (VIB); and Department of Neurosciences (B.G., K.P.), Laboratory for Molecular Neurobiomarker Research, Leuven, Belgium.
MD, PhD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Koen Poesen
From the Department of Neurology (N.V., M.S., P.V.D.), Department of Ophthalmology (C.C.), and Laboratory Medicine (X.B., K.P.), University Hospital Leuven; Department of Microbiology and Immunology (X.B.), Experimental Laboratory Immunology, Leuven, Belgium; Department of Immunology (T.V.), St Eloi Hospital, Montpellier University, France; Department of Neurosciences (P.V.D.), Laboratory for Neurobiology; Vesalius Research Center (P.V.D.), Flemish Institute for Biotechnology (VIB); and Department of Neurosciences (B.G., K.P.), Laboratory for Molecular Neurobiomarker Research, Leuven, Belgium.
PharmD, PhD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Full PDF
Citation
Negative commercial screening test for paraneoplastic antibodies in a case of opsoclonus
Nicolas Vandenbussche, Catherine Cassiman, Maarten Schrooten, Benjamin Gille, Xavier Bossuyt, Thierry Vincent, Philip Van Damme, Koen Poesen
Neurol Neuroimmunol Neuroinflamm Mar 2017, 4 (2) e329; DOI: 10.1212/NXI.0000000000000329

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Permissions

Make Comment

See Comments

Downloads
887

Share

  • Article
  • Figures & Data
  • Info & Disclosures
Loading

The diagnosis of a paraneoplastic syndrome (PNS) is challenging as it comprises a group of clinically heterogeneous entities, all related to a coexistent, but sometimes occult, malignancy.1 The detection of paraneoplastic antibodies aids the clinician to establish the diagnosis of a PNS.2 Paraneoplastic antibodies are screened for by means of immunohistochemistry or indirect immunofluorescence on cerebellar slices.2 Cerebellar substrates that can be used for screening for paraneoplastic antibodies are commercially available.3

Such commercial screening was applied to screen the serum and CSF of a 48-year-old woman presenting with a subacute onset of oscillopsia and diplopia. No family history of neurologic diseases was present. Two months before, she experienced the initial symptoms of anorexia, nausea, and balancing problems. Two weeks before admission, she experienced the first signs of multidirectional binocular diplopia and oscillopsia. Neurologic examination revealed a normal mental and cognitive status. Ocular motility showed full-range eye movements. The patient mentioned binocular diplopia on lateral gaze and downgaze. Initially, bursts of ocular flutter were noticed, confirmed by video-oculography, which evolved over time into a constant opsoclonus. This opsoclonus caused significant visual impairment with a drop of visual acuity to logMAR 0.7. She had a normal motor and sensory examination. The osteotendinous reflexes were brisk without pathologic reflexes. Gait was broad-based ataxic, without overt appendicular ataxia. In a later phase, she mentioned infrequent shock-like movements of arms and head, reminiscent of myoclonus. Logopedic examination revealed prolonged oral processing with delayed initiation of swallowing and incomplete elevation of the larynx, without further objective abnormalities during deglutition. CT and MRI of the brain and brainstem and peripheral otovestibular tests revealed no abnormalities.

An autoimmune screening was negative in the serum (table). The positive findings of an extensive biochemical, microbiological, and cytologic examination of the CSF are presented in the table. Initial screening for paraneoplastic antibodies on admission and the next day was negative in the serum and in the CSF (table). Negativity was independently confirmed using the same commercial assay (table). Serum tests for anti–NMDA receptor antibody, anti–voltage-gated calcium channels antibody, anti-ganglioside/sulfatide antibodies, and anti–glutamic acid decarboxylase I/II antibody were negative as well.

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table

Serum and CSF results of interest for the case

A 2-[18F] fluoro-2-deoxy-d-glucose PET confirmed a suspicious mammography, revealing a strong hypermetabolic region in the right breast, without further evidence of hypermetabolic lymph nodes or distant metastasis. Histologic examination of a broadly excised breast tumor section showed a grade 2 moderately differentiated invasive ductal adenocarcinoma and 3 negative sentinel nodes. A seronegative PNS with ocular opsoclonus and gait ataxia was diagnosed. Oral methylprednisolone and IV plasmapheresis had no significant effect.1 Clonazepam and gabapentin relieved some of the oscillopsia. Tamoxifen was started 2 weeks after surgery. Adjuvant radiotherapy (daily fractions of 2.66 Gy to a total dose of 42.56 Gy) and chemotherapy, consisting of 4 cycles of epirubicin and cyclophosphamide followed by 12 cycles of Taxotere, was started 7 and 13 weeks after surgery, respectively. Opsoclonus completely disappeared, and hence visual acuity improved accordingly (logMAR 0.1). Gait ataxia improved significantly, allowing her to walk without walking aids again.

Given the negative test results for antibodies contrasting with a clear PNS, the serum and the CSF samples taken at admission were reassessed for paraneoplastic antibodies by a noncommercial immunohistochemical screening using rat brain tissue.2 This screening suggested the presence of anti-Ri antibodies (table). The latter was confirmed using an immunoblot of recombinant protein similar to the one published before2 and a commercial immunodot assay as well (table).

Here, we report that a commercial screening for paraneoplastic antibodies, which is applied worldwide,3 failed to detect anti-Ri antibody in the serum and in the CSF of a patient with a PNS. Only one relatively small study addressed the sensitivity of a commercial screening test before, and that results were positive in 2/2 Ri, 6/6 Hu, 3/5 Yo, and 0/2 Ma2 patients' serum, without, unlike our case, any CSF antibodies status available.3 A screening for the sake of cost-efficiency requires a high sensitivity to avoid false-negative results as the presence of a paraneoplastic antibody directs the clinician toward the diagnosis of a PNS, especially in clinically doubtful cases.4 Providing clinical information along with the laboratory request enables the clinical pathologist to direct testing as proposed by international guidelines, which might avoid false-negative results when clinical suspicion is high.4 Our case illustrates that screening for paraneoplastic antibodies by commercially available tissue-based assay might miss individual cases that are detected by other methods.5

Acknowledgments

Acknowledgment: The authors thank Prof. Dr. Dalmau (Service of Neurology, Hospital Clínic, University of Barcelona; Adjunct Professor Neurology, University of Pennsylvania) and his team for supplying the data of the screening using rat brain tissue and the data of the immunoblot, and for critically revising the manuscript.

Footnotes

  • Author contributions: Nicolas Vandenbussche: sample collection, design and conceptualization of the study, data generation, data interpretation, and drafting of the manuscript. Catherine Cassiman: design and conceptualization of the study, data generation, data interpretation, and revising the manuscript for intellectual content. Maarten Schrooten: sample collection, data generation, data interpretation, and revising the manuscript for intellectual content. Benjamin Gille: sample collection and revising the manuscript for intellectual content. Xavier Bossuyt and Thierry Vincent: data generation, data interpretation, and revising the manuscript for intellectual content. Philip Van Damme: sample collection, design and conceptualization of the study, data generation, data interpretation, and revising the manuscript for intellectual content. Koen Poesen: design and conceptualization of the study, data generation, data interpretation, and drafting of the manuscript.

  • Study funding: No targeted funding.

  • Disclosure: N. Vandenbussche, C. Cassiman, M. Schrooten, B. Gille, X. Bossuyt, and T. Vincent report no disclosures. P. Van Damme received research support from FWO-Vlaanderen. K. Poesen reports no disclosures. Go to Neurology.org/nn for full disclosure forms. The Article Processing Charge was paid by the authors.

  • Received October 11, 2016.
  • Accepted in final form December 13, 2016.
  • Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

References

  1. 1.↵
    1. Rosenfeld MR,
    2. Dalmau J
    . Diagnosis and management of paraneoplastic neurologic disorders. Curr Treat Options Oncol 2013;14:528–538.
    OpenUrlCrossRefPubMed
  2. 2.↵
    1. Dalmau J,
    2. Gultekin SH,
    3. Voltz R, et al
    . Ma1, a novel neuron- and testis-specific protein, is recognized by the serum of patients with paraneoplastic neurological disorders. Brain 1999;122:27–39.
    OpenUrlAbstract/FREE Full Text
  3. 3.↵
    1. Tampoia M,
    2. Zucano A,
    3. Antico A, et al
    . Diagnostic accuracy of different immunological methods for the detection of antineuronal antibodies in paraneoplastic neurological syndromes. Immunol Invest 2010;39:186–195.
    OpenUrlPubMed
  4. 4.↵
    1. Hoftberger R,
    2. Dalmau J,
    3. Graus F
    . Clinical neuropathology practice guide 5-2012: updated guideline for the diagnosis of antineuronal antibodies. Clin Neuropathol 2012;31:337–341.
    OpenUrlPubMed
  5. 5.↵
    1. Knudsen A,
    2. Monstad SE,
    3. Dorum A, et al
    . Ri antibodies in patients with breast, ovarian or small cell lung cancer determined by a sensitive immunoprecipitation technique. Cancer Immunol Immunother 2006;55:1280–1284.
    OpenUrlCrossRefPubMed

Letters: Rapid online correspondence

No comments have been published for this article.
Comment

REQUIREMENTS

You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.

Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.

If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.

Submission specifications:

  • Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
  • Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
  • Submit only on articles published within 6 months of issue date.
  • Do not be redundant. Read any comments already posted on the article prior to submission.
  • Submitted comments are subject to editing and editor review prior to posting.

More guidelines and information on Disputes & Debates

Compose Comment

More information about text formats

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.
Author Information
NOTE: The first author must also be the corresponding author of the comment.
First or given name, e.g. 'Peter'.
Your last, or family, name, e.g. 'MacMoody'.
Your email address, e.g. [email protected]
Your role and/or occupation, e.g. 'Orthopedic Surgeon'.
Your organization or institution (if applicable), e.g. 'Royal Free Hospital'.
Publishing Agreement
NOTE: All authors, besides the first/corresponding author, must complete a separate Publishing Agreement Form and provide via email to the editorial office before comments can be posted.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.

Vertical Tabs

You May Also be Interested in

Back to top
  • Article
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Disclosures
Advertisement

Hastening the Diagnosis of Amyotrophic Lateral Sclerosis

Dr. Brian Callaghan and Dr. Kellen Quigg

► Watch

Related Articles

  • No related articles found.

Topics Discussed

  • Oscillopsia
  • All Immunology
  • Paraneoplastic syndrome

Alert Me

  • Alert me when eletters are published

Recommended articles

  • Brief Communications
    Response to cancer therapy in a patient with a paraneoplastic choreiform disorder
    David Croteau, Alaa Owainati, Josep Dalmau et al.
    Neurology, August 28, 2001
  • Articles
    GABAB receptor antibodies in limbic encephalitis and anti-GAD–associated neurologic disorders
    A. Boronat, L. Sabater, A. Saiz et al.
    Neurology, February 28, 2011
  • Article
    Clinical spectrum and diagnostic pitfalls of neurologic syndromes with Ri antibodies
    Claire Simard, Alberto Vogrig, Bastien Joubert et al.
    Neurology: Neuroimmunology & Neuroinflammation, March 13, 2020
  • Resident & Fellow Section
    Clinical Reasoning: A 16-year-old girl with ataxia, oscillopsia, and behavioral changes
    Andrew Silverman, Chindhuri Selvadurai, John Picard et al.
    Neurology, March 31, 2020
Neurology - Neuroimmunology Neuroinflammation: 11 (1)

Articles

  • Articles
  • Issues
  • Popular Articles

About

  • About the Journals
  • Ethics Policies
  • Editors & Editorial Board
  • Contact Us
  • Advertise

Submit

  • Author Center
  • Submit a Manuscript
  • Information for Reviewers
  • AAN Guidelines
  • Permissions

Subscribers

  • Subscribe
  • Sign up for eAlerts
  • RSS Feed
Site Logo
  • Visit neurology Template on Facebook
  • Follow neurology Template on Twitter
  • Visit Neurology on YouTube
  • Neurology
  • Neurology: Clinical Practice
  • Neurology: Education
  • Neurology: Genetics
  • Neurology: Neuroimmunology & Neuroinflammation
  • AAN.com
  • Continuum
  • Brain & Life
  • Neurology Today

Wolters Kluwer Logo

Neurology: Neuroimmunology & Neuroinflammation
Online ISSN: 2332-7812

© 2023 American Academy of Neurology

  • Privacy Policy
  • Feedback
  • Advertise