Abstract
Cerebellar ataxia associated with glutamic acid decarboxylase autoantibodies (GAD-ab) is a rare and usually slow progressive disease with moderate to severe gait and limb ataxia, dysarthria, and nystagmus. The treatment for this condition is still being discussed. We report the cases of three patients with GAD-ab cerebellar ataxia treated successively with intravenous immunoglobulin (IVIg) and rituximab. Symptoms improved in one case after rituximab therapy and were stabilized in another after a combined therapy of IVIg and rituximab. The third patient continued to worsen despite these treatments. We conclude that IVIg and rituximab therapy could improve or stabilize GAD-ab cerebellar ataxia. Early treatment, the lack of cerebellar atrophy on magnetic resonance imaging, and a subacute onset of the symptoms could be decisive prognostic factors.
Similar content being viewed by others
References
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;131:2553–63.
Nanri K, Niwa H, Mitoma H, Takei A, Ikeda J, Harada T, et al. Low-titer anti-GAD-antibody-positive cerebellar ataxia. Cerebellum. 2013;12(2):171–5.
Abele M, Weller M, Mescheriakov S, Bürk K, Dichgans J, Klockgether T. Cerebellar ataxia with glutamic acid decarboxylase autoantibodies. Neurology. 1999;52:857–9.
Pedroso JL, Braga-Neto P, Dutra LA, Barsottini OG. Cerebellar ataxia associated to anti-glutamic acid decarboxylase autoantibody (anti-GAD): partial improvement with intravenous immunoglobulin therapy. Arq Neuropsiquiatr. 2011;69:993.
Lauria G, Pareyson D, Pitzolu MG, Bazzigaluppi E. Excellent response to steroid treatment in anti-GAD cerebellar ataxia. Lancet Neurol. 2003;2:634–5.
McFarland NR, Login IS, Vernon S, Burns TM. Improvement with corticosteroids and azathioprine in GAD65-associated cerebellar ataxia. Neurology. 2006;67:1308–9.
Bonnan M, Cabre P, Olindo S, Signate A, Saint-Vil M, Smadja D. [Steroid treatment in four cases of anti-GAD cerebellar ataxia]. Rev Neurol (Paris). 2008;164:427–33.
Awad A, Stüve O, Mayo M, Alkawadri R, Estephan B. Anti-glutamic acid decarboxylase antibody-associated ataxia as an extrahepatic autoimmune manifestation of hepatitis C infection: a case report. Case Rep Neurol Med. 2011;2011:975152.
Dalakas MC, Fujii M, Li M, Lutfi B, Kyhos J, McElroy B. High-dose intravenous immune globulin for stiff-person syndrome. N Engl J Med. 2001;345:1870–6.
Fekete R, Jankovic J. Childhood stiff-person syndrome improved with rituximab. Case Rep Neurol. 2012;4:92–6.
Bacorro EA, Tehrani R. Stiff-person syndrome: persistent elevation of glutamic acid decarboxylase antibodies despite successful treatment with rituximab. J Clin Rheumatol. 2010;16:237–9.
Venhoff N, Rizzi M, Salzer U, Bossaller L, Thoden J, Eibel H, et al. Monozygotic twins with stiff person syndrome and autoimmune thyroiditis: rituximab inefficacy in a double-blind, randomised, placebo controlled crossover study. Ann Rheum Dis. 2009;68:1506–8.
Mitoma H, Song SY, Ishida K, Yamakuni T, Kobayashi T, Mizusawa H. Presynaptic impairment of cerebellar inhibitory synapses by an autoantibody to glutamate decarboxylase. J Neurol Sci. 2000;175(1):40–4.
Manto M-U, Laute M-A, 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.
Ishida K, Mitoma H, Wada Y, Oka T, Shibahara J, Saito Y, et al. Selective loss of Purkinje cells in a patient with anti-glutamic acid decarboxylase antibody-associated cerebellar ataxia. J Neurol Neurosurg Psychiatr. 2007;78:190–2.
Hampe CS, Petrosini L, De Bartolo P, Caporali P, Cutuli D, Laricchiuta D, et al. Monoclonal antibodies to 65 kDa glutamate decarboxylase induce epitope specific effects on motor and cognitive functions in rats. Orphanet J Rare Dis. 2013;8:82.
Chang T, Alexopoulos H, McMenamin M, Carvajal-González A, Alexander SK, Deacon R, et al. Neuronal surface and glutamic acid decarboxylase autoantibodies in nonparaneoplastic stiff person syndrome. JAMA Neurol 2013;doi:10.1001
Cao BB, Huang Y, Lu JH, Xu FF, Qiu YH, Peng YP. Cerebellar fastigial nuclear GABAergic projections to the hypothalamus modulate immune function. Brain Behav Immun. 2013;27(1):80–90.
Rakocevic G, Raju R, Semino-Mora C, Dalakas MC. Stiff person syndrome with cerebellar disease and high-titer anti-GAD antibodies. Neurology. 2006;67:1068–70.
Conflict of Interest
On behalf of all authors, the corresponding author states that there is no conflict of interest.
Patient Consent
The patients' explicit consent was obtained before publication.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Planche, V., Marques, A., Ulla, M. et al. Intravenous Immunoglobulin and Rituximab for Cerebellar Ataxia with Glutamic Acid Decarboxylase Autoantibodies. Cerebellum 13, 318–322 (2014). https://doi.org/10.1007/s12311-013-0534-3
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12311-013-0534-3