Advertisement

The Cerebellum

, Volume 13, Issue 3, pp 318–322 | Cite as

Intravenous Immunoglobulin and Rituximab for Cerebellar Ataxia with Glutamic Acid Decarboxylase Autoantibodies

  • Vincent Planche
  • Ana Marques
  • Miguel Ulla
  • Marc Ruivard
  • Franck Durif
Original Paper

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.

Keywords

Glutamic acid decarboxylase antibodies Cerebellar ataxia Gait disorders Intravenous immunoglobulin Rituximab Neuro-immunity 

Notes

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.

References

  1. 1.
    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.PubMedCrossRefGoogle Scholar
  2. 2.
    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.PubMedCrossRefGoogle Scholar
  3. 3.
    Abele M, Weller M, Mescheriakov S, Bürk K, Dichgans J, Klockgether T. Cerebellar ataxia with glutamic acid decarboxylase autoantibodies. Neurology. 1999;52:857–9.PubMedCrossRefGoogle Scholar
  4. 4.
    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.PubMedCrossRefGoogle Scholar
  5. 5.
    Lauria G, Pareyson D, Pitzolu MG, Bazzigaluppi E. Excellent response to steroid treatment in anti-GAD cerebellar ataxia. Lancet Neurol. 2003;2:634–5.PubMedCrossRefGoogle Scholar
  6. 6.
    McFarland NR, Login IS, Vernon S, Burns TM. Improvement with corticosteroids and azathioprine in GAD65-associated cerebellar ataxia. Neurology. 2006;67:1308–9.PubMedCrossRefGoogle Scholar
  7. 7.
    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.CrossRefGoogle Scholar
  8. 8.
    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.PubMedCentralPubMedGoogle Scholar
  9. 9.
    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.PubMedCrossRefGoogle Scholar
  10. 10.
    Fekete R, Jankovic J. Childhood stiff-person syndrome improved with rituximab. Case Rep Neurol. 2012;4:92–6.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    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.PubMedCrossRefGoogle Scholar
  12. 12.
    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.PubMedCrossRefGoogle Scholar
  13. 13.
    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.PubMedCrossRefGoogle Scholar
  14. 14.
    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.PubMedCrossRefGoogle Scholar
  15. 15.
    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.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    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.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    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:10.1001Google Scholar
  18. 18.
    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.PubMedCrossRefGoogle Scholar
  19. 19.
    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.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Vincent Planche
    • 1
  • Ana Marques
    • 1
  • Miguel Ulla
    • 1
  • Marc Ruivard
    • 2
  • Franck Durif
    • 1
  1. 1.Service de NeurologieCHU Gabriel MontpiedClermont-FerrandFrance
  2. 2.Service de Médecine InterneCHU EstaingClermont-FerrandFrance

Personalised recommendations