The Cerebellum

, Volume 12, Issue 2, pp 171–175 | Cite as

Low-Titer Anti-GAD-Antibody-Positive Cerebellar Ataxia

  • Kazunori Nanri
  • Hisayoshi Niwa
  • Hiroshi Mitoma
  • Asako Takei
  • Junko Ikeda
  • Toshihide Harada
  • Mitsunori Okita
  • Masafumi Takeguchi
  • Takeshi Taguchi
  • Hidehiro Mizusawa
Original Paper


The majority of cases of anti-glutamic acid decarboxylase (GAD)-antibody-positive cerebellar ataxia are reported to have high levels of anti-GAD antibody, and the diagnostic value of low titers of anti-GAD antibody in a patient with cerebellar ataxia is still unknown. The purpose of this study was to verify the characteristics of low-titer-anti-GAD-antibody-positive cerebellar ataxia patients and the diagnostic value of low titers of anti-GAD antibody in patients with cerebellar ataxia. The subjects were six patients positive for low-titer GAD antibody (<100 U/mL). We examined them with MRI, including voxel-based morphometry, and with single-photon emission computed tomography and monitored the GAD antibody index in the cerebrospinal fluid. The levels of antineuronal, antigliadin, anti-SS-A, antithyroid antibodies, and of vitamins E, B1, and B12 were determined. Thoracic and abdominal CT scans were performed to exclude a paraneoplastic origin. We treated three patients with immunotherapy. All cases showed cortical cerebellar atrophy. The GAD antibody index in three of the five patients reviewed was >1.0. Two of the six patients were thyroid antibody-positive, and one was both antinuclear- and anti-SS-A antibody-positive. After the administration of immunotherapy to three patients, two showed clear effectiveness, and one, transient effectiveness. Effectiveness was greatest in the two patients with familial occurrence of the disease. In cerebellar ataxia, regardless of family history or isolated illness, it is critical to measure the GAD antibody level, and, even with a low titer level, if the result is positive, immunotherapy should be considered.


Anti-GAD antibody Cerebellar ataxia Low titer Steroid therapy IVIg 



The authors express their gratitude to Mr. C. W. P. Reynolds, associated with the Department of International Medical Communications of Tokyo Medical University, for his careful revision of the English language of this paper.

Conflict of interests



  1. 1.
    Honnorat J, Saiz A, Giometto B, Vincent A, Brieva L, de Andres C, et al. Cerebellar ataxia with anti-glutamic acid decarboxylase antibodies: study of 14 patients. Arch Neurol. 2001;58:225–30.PubMedCrossRefGoogle Scholar
  2. 2.
    Birand B, Cabre P, Bonnan M, Olindo S, Smadja D. A new case of cerebellar ataxia with anti-GAD antibodies treated with corticosteroids and initially seronegative. Rev Med Interne. 2006;27:616–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Saiz A, Blanco Y, Sabater L, González F, Bataller L, Casamitjana R, et al. Spectrum of neurological syndromes associated with glutamic acid decarboxylase antibodies: diagnostic clues for this association. Brain. 2008;131(Pt 10):2553–63.PubMedCrossRefGoogle Scholar
  4. 4.
    Lee YS, Ng WY, Thai AC, Lui KF, Loke KY. Prevalence of ICA and GAD antibodies at initial presentation of type 1 diabetes mellitus in Singapore children. J Pediatr Endocrinol Metab. 2001;14:767–72.PubMedGoogle Scholar
  5. 5.
    Dalakas MC. The role of IVIg in the treatment of patients with stiff person syndrome and other neurological diseases associated with anti-GAD antibodies. J Neurol. 2005;252 Suppl 1:I19–25.PubMedCrossRefGoogle Scholar
  6. 6.
    Nanri K, Okita M, Takeguchi M, Taguchi T, Ishiko T, Saito H, et al. Intravenous immunoglobulin therapy for autoantibody-positive cerebellar ataxia. Intern Med. 2009;48:783–90.PubMedCrossRefGoogle Scholar
  7. 7.
    Ikeda J, Harada T, Kamei H, Nakamura S. Autoantibody to glutamate decarboxylase in a patient with spinocerebellar degeneration and Sjögren syndrome. No To Shinkei. 1998;50:177–80.PubMedGoogle Scholar
  8. 8.
    Nociti V, Frisullo G, Tartaglione T, Patanella AK, Iorio R, Tonali PA, et al. Refractory generalized seizures and cerebellar ataxia associated with anti-GAD antibodies responsive to immunosuppressive treatment. Eur J Neurol. 2010;17:e5.PubMedCrossRefGoogle Scholar
  9. 9.
    Virgilio R, Corti S, Agazzi P, Santoro D, Lanfranconi S, Candelise L, et al. Effect of steroid treatment in cerebellar ataxia associated with anti-glutamic acid decarboxylase antibodies. J Neurol Neurosurg Psychiatry. 2009;80:95–6.PubMedCrossRefGoogle Scholar
  10. 10.
    Dalakas MC, Li M, Fujii M, Jacobowitz DM. Stiff person syndrome: quantification, specificity, and intrathecal synthesis of GAD65 antibodies. Neurology. 2001;57:780–4.PubMedCrossRefGoogle Scholar
  11. 11.
    Mitoma H, Ishida K, Shizuka-Ikeda M, Mizusawa H. Dual impairment of GABAA- and GABAB-receptor-mediated synaptic responses by autoantibodies to glutamic acid decarboxylase. J Neurol Sci. 2003;208:51–6.PubMedCrossRefGoogle Scholar
  12. 12.
    Manto MU, Laute MA, Aguera M, Rogemond V, Pandolfo M, Honnorat J. Effects of anti-glutamic acid decarboxylase antibodies associated with neurological diseases. Ann Neurol. 2007;61:544–51.PubMedCrossRefGoogle Scholar
  13. 13.
    Manto MU, Hampe CS, Rogemond V, Honnorat J. Respective implications of glutamate decarboxylase antibodies in stiff person syndrome and cerebellar ataxia. Orphanet J Rare Dis. 2011;6:3.PubMedCrossRefGoogle Scholar
  14. 14.
    Vianello M, Tavolato B, Armani M, Giometto B. Cerebellar ataxia associated with anti-glutamic acid decarboxylase autoantibodies. Cerebellum. 2003;2:77–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Manto M, Jissendi P. Brain imaging in cerebellar ataxia associated with autoimmune polyglandular syndrome type 2. J Neuroimaging. 2012;22:308–11.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Kazunori Nanri
    • 1
  • Hisayoshi Niwa
    • 2
  • Hiroshi Mitoma
    • 3
  • Asako Takei
    • 4
  • Junko Ikeda
    • 5
  • Toshihide Harada
    • 6
  • Mitsunori Okita
    • 1
  • Masafumi Takeguchi
    • 1
  • Takeshi Taguchi
    • 1
  • Hidehiro Mizusawa
    • 7
  1. 1.Department of NeurologyTokyo Medical University Hachioji Medical CenterHachiojiJapan
  2. 2.Department of NeurologyKARIYA TOYOTA General HospitalKariyaJapan
  3. 3.Post-graduate Clinical Residents’ CenterTokyo Medical UniversityTokyoJapan
  4. 4.Hokuyukai Neurology HospitalSapporoJapan
  5. 5.Department of NeurologyHiroshima City General Rehabilitation CenterHiroshimaJapan
  6. 6.Department of Health Services Management, Faculty of Health and Welfare Graduate Course in Integrated Human SciencesHiroshima International UniversityHiroshimaJapan
  7. 7.Department of Neurology and Neurological ScienceGraduate SchoolTokyoJapan

Personalised recommendations