Abstract
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.
Similar content being viewed by others
References
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.
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.
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.
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.
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.
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.
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.
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.
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.
Dalakas MC, Li M, Fujii M, Jacobowitz DM. Stiff person syndrome: quantification, specificity, and intrathecal synthesis of GAD65 antibodies. Neurology. 2001;57:780–4.
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.
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.
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.
Vianello M, Tavolato B, Armani M, Giometto B. Cerebellar ataxia associated with anti-glutamic acid decarboxylase autoantibodies. Cerebellum. 2003;2:77–9.
Manto M, Jissendi P. Brain imaging in cerebellar ataxia associated with autoimmune polyglandular syndrome type 2. J Neuroimaging. 2012;22:308–11.
Acknowledgments
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
None
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Nanri, K., Niwa, H., Mitoma, H. et al. Low-Titer Anti-GAD-Antibody-Positive Cerebellar Ataxia. Cerebellum 12, 171–175 (2013). https://doi.org/10.1007/s12311-012-0411-5
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12311-012-0411-5