---
_id: '2598'
abstract:
- lang: eng
  text: "There are many types of cerebellar ataxia, including ataxia due to congenital
    or metabolic disorders and a paraneoplastic form in patients with gynecologic
    cancer, breast cancer, lung cancer, or Hodgkin's disease.1 This paraneoplastic
    syndrome is the only type of cerebellar ataxia associated with autoantibodies
    against neuronal antigens. Often, the neuronal antigens are aberrantly expressed
    by the tumor cells.2-4 The antineuronal autoantibodies are believed to cause cerebellar
    ataxia, but this is unproved.5,6 In Hodgkin's disease, the lymphoma precedes the
    ataxia by months to years in 80 percent of patients, and ataxia often occurs during
    a prolonged complete remission.4 Among patients with this type of ataxia, 30 percent
    have anti–Purkinje-cell antibodies, some of which have the features of the neuronal
    antibody anti-Tr.4,7\r\n\r\nWe identified a new autoantibody in two patients with
    severe cerebellar ataxia that developed while they were in remission from Hodgkin's
    disease. The antibody reacts specifically with the metabotropic glutamate receptor
    mGluR1 in mouse brain. Metabotropic glutamate receptors belong to a large family
    of cell-surface receptors that transmit signals into the cell by coupling to guanine
    nucleotide-binding proteins (G proteins) in the cytoplasm. Purified IgG from the
    serum of both patients blocked the glutamate-stimulated formation of inositol
    phosphates in Chinese-hamster-ovary (CHO) cells that expressed mGluR1α, and the
    injection of IgG from serum or cerebrospinal fluid into the cerebellar subarachnoid
    space of mice caused severe, reversible ataxia. These results indicate that antineuronal
    autoantibodies can cause disease of the central nervous system by blocking neuronal
    receptors."
acknowledgement: "Supported in part by the Ministry of Education, Science, and Culture
  of Japan (Dr. Nakanishi and Dr. Shigemoto); CREST of Japan Science and Technology
  Corporation (Dr. Shigemoto); the Life Sciences Foundation (Dr. De Zeeuw); NWO (Dr.
  De Zeeuw and Dr. De Leeuw); and the Human Frontier Science Program (Dr. De Zeeuw
  and Dr. Shigemoto).\r\nDrs. Sillevis Smitt and Kinoshita contributed equally to
  the article. We are indebted to A. Aiba for providing mGluR1-deficient mice; to
  T. Maruyama for providing human mGluR1-expressing CHO cells; to H. Jingami for helpful
  discussion; to A. Uesugi for photographic assistance; to M. van den Bent and C.
  Gaillard for clinical information on the patients; and to J. van der Burg, S.K.E.
  Koekkoek, K.J. Reus, and C. Vermeer for technical assistance."
article_processing_charge: No
article_type: original
author:
- first_name: Peter
  full_name: Sillevis Smitt, Peter
  last_name: Sillevis Smitt
- first_name: Ayae
  full_name: Kinoshita, Ayae
  last_name: Kinoshita
- first_name: Bertie
  full_name: De Leeuw, Bertie
  last_name: De Leeuw
- first_name: Wiebe
  full_name: Moll, Wiebe
  last_name: Moll
- first_name: Michiel
  full_name: Coesmans, Michiel
  last_name: Coesmans
- first_name: Dick
  full_name: Jaarsma, Dick
  last_name: Jaarsma
- first_name: Sonja
  full_name: Henzen Logmans, Sonja
  last_name: Henzen Logmans
- first_name: Charles
  full_name: Vecht, Charles
  last_name: Vecht
- first_name: Chris
  full_name: De Zeeuw, Chris
  last_name: De Zeeuw
- first_name: Naotaka
  full_name: Sekiyama, Naotaka
  last_name: Sekiyama
- first_name: Shigetada
  full_name: Nakanishi, Shigetada
  last_name: Nakanishi
- first_name: Ryuichi
  full_name: Shigemoto, Ryuichi
  id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
  last_name: Shigemoto
  orcid: 0000-0001-8761-9444
citation:
  ama: Sillevis Smitt P, Kinoshita A, De Leeuw B, et al. Paraneoplastic cerebellar
    ataxia due to autoantibodies against a glutamate receptor. <i>New England Journal
    of Medicine</i>. 2000;342(1):21-27. doi:<a href="https://doi.org/10.1056/NEJM200001063420104">10.1056/NEJM200001063420104</a>
  apa: Sillevis Smitt, P., Kinoshita, A., De Leeuw, B., Moll, W., Coesmans, M., Jaarsma,
    D., … Shigemoto, R. (2000). Paraneoplastic cerebellar ataxia due to autoantibodies
    against a glutamate receptor. <i>New England Journal of Medicine</i>. Massachussetts
    Medical Society. <a href="https://doi.org/10.1056/NEJM200001063420104">https://doi.org/10.1056/NEJM200001063420104</a>
  chicago: Sillevis Smitt, Peter, Ayae Kinoshita, Bertie De Leeuw, Wiebe Moll, Michiel
    Coesmans, Dick Jaarsma, Sonja Henzen Logmans, et al. “Paraneoplastic Cerebellar
    Ataxia Due to Autoantibodies against a Glutamate Receptor.” <i>New England Journal
    of Medicine</i>. Massachussetts Medical Society, 2000. <a href="https://doi.org/10.1056/NEJM200001063420104">https://doi.org/10.1056/NEJM200001063420104</a>.
  ieee: P. Sillevis Smitt <i>et al.</i>, “Paraneoplastic cerebellar ataxia due to
    autoantibodies against a glutamate receptor,” <i>New England Journal of Medicine</i>,
    vol. 342, no. 1. Massachussetts Medical Society, pp. 21–27, 2000.
  ista: Sillevis Smitt P, Kinoshita A, De Leeuw B, Moll W, Coesmans M, Jaarsma D,
    Henzen Logmans S, Vecht C, De Zeeuw C, Sekiyama N, Nakanishi S, Shigemoto R. 2000.
    Paraneoplastic cerebellar ataxia due to autoantibodies against a glutamate receptor.
    New England Journal of Medicine. 342(1), 21–27.
  mla: Sillevis Smitt, Peter, et al. “Paraneoplastic Cerebellar Ataxia Due to Autoantibodies
    against a Glutamate Receptor.” <i>New England Journal of Medicine</i>, vol. 342,
    no. 1, Massachussetts Medical Society, 2000, pp. 21–27, doi:<a href="https://doi.org/10.1056/NEJM200001063420104">10.1056/NEJM200001063420104</a>.
  short: P. Sillevis Smitt, A. Kinoshita, B. De Leeuw, W. Moll, M. Coesmans, D. Jaarsma,
    S. Henzen Logmans, C. Vecht, C. De Zeeuw, N. Sekiyama, S. Nakanishi, R. Shigemoto,
    New England Journal of Medicine 342 (2000) 21–27.
date_created: 2018-12-11T11:58:35Z
date_published: 2000-01-06T00:00:00Z
date_updated: 2023-05-03T11:14:19Z
day: '06'
doi: 10.1056/NEJM200001063420104
extern: '1'
external_id:
  pmid:
  - '10620645'
intvolume: '       342'
issue: '1'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://www.nejm.org/doi/full/10.1056/nejm200001063420104
month: '01'
oa: 1
oa_version: None
page: 21 - 27
pmid: 1
publication: New England Journal of Medicine
publication_identifier:
  issn:
  - 0028-4793
publication_status: published
publisher: Massachussetts Medical Society
publist_id: '4300'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Paraneoplastic cerebellar ataxia due to autoantibodies against a glutamate
  receptor
type: journal_article
user_id: ea97e931-d5af-11eb-85d4-e6957dddbf17
volume: 342
year: '2000'
...