GABAB receptor antibodies in limbic encephalitis and anti-GAD–associated neurologic disorders
Abstract
Background:
γ-Aminobutyric acid-B receptor antibodies (GABABR-ab) were recently described in 15 patients with limbic encephalitis (LE), associated with small-cell lung cancer (SCLC) or with concurrent glutamic acid decarboxylase (GAD) antibodies. We analyzed the frequency of GABABR-ab in 147 patients with LE or neurologic syndromes associated with GAD-ab.
Methods:
We examined the presence of GABABR-ab in 70 patients with LE (33 paraneoplastic with onconeural antibodies, 18 paraneoplastic without onconeural antibodies [5 with Gad-ab], and 19 idiopathic with either GAD-ab [5 patients] or seronegative) and 77 patients with GAD-ab-associated neurologic syndromes other than LE (29 stiff-person syndrome, 28 cerebellar ataxia, 14 epilepsy, and 6 with diverse paraneoplastic neurologic syndromes). GABABR-ab were analyzed in serum or CSF by indirect immunofluorescence on HEK293 cells transfected with GABAB1 and GABAB2 receptor subunits.
Results:
GABABR-ab were detected in 10 of the 70 patients with LE (14%). Eight had SCLC and 2 were idiopathic. One of the 8 patients with LE with SCLC had an additional onconeural antibody (Hu) and 2 GAD-ab. GABABR-ab were identified in 7 (70%) of the 10 patients with LE and SCLC without onconeural antibodies. GABABR-ab antibodies were not found in patients with GAD-ab and stiff-person syndrome, idiopathic cerebellar ataxia, or epilepsy. However, one patient with GAD-ab, paraneoplastic cerebellar ataxia, and anaplastic carcinoid of the thymus also presented GABABR-ab.
Conclusions:
GABABR-ab are the most common antibodies found in LE associated with SCLC previously considered “seronegative.” In patients with GAD-ab, the frequency of GABABR-ab is low and only observed in the context of cancer.
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REFERENCES
1.
Graus F, Saiz A, Dalmau J. Antibodies and neuronal autoimmune disorders of the CNS. J Neurol 2010;257:509–517.
2.
Dalmau J, Gleichman AJ, Hughes EG, et al. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol 2008;7:1091–1098.
3.
Lai M, Hughes EG, Peng X, et al. AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location. Ann Neurol 2009;65:424–434.
4.
Lancaster E, Lai M, Peng X, et al. Antibodies to the GABA(B) receptor in limbic encephalitis with seizures: case series and characterisation of the antigen. Lancet Neurol 2010;9:67–76.
5.
Lai M, Huijbers MG, Lancaster E, et al. Investigation of LGI1 as the antigen in limbic encephalitis previously attributed to potassium channels: a case series. Lancet Neurol 2010;9:776–785.
6.
Graus F, Saiz A, Lai M, et al. Neuronal surface antigen antibodies in limbic encephalitis: clinical-immunologic associations. Neurology 2008;71:930–936.
7.
Graus F, Delattre JY, Antoine JC, et al. Recommended diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry 2004;75:1135–1140.
8.
Saiz A, Blanco Y, Sabater L, et al. Spectrum of neurological syndromes associated with glutamic acid decarboxylase antibodies: diagnostic clues for this association. Brain 2008;131:2553–2563.
9.
Sabater L, Gómez-Choco M, Saiz A, Graus F. BR serine/threonine kinase 2: a new autoantigen in paraneoplastic limbic encephalitis. J Neuroimmunol 2005;170:186–190.
10.
Zuliani L, Saiz A, Tavolato B, Giometto B, Vincent A, Graus F. Paraneoplastic limbic encephalitis associated with potassium channel antibodies: value of anti-glial nuclear antibodies in identifying the tumour. J Neurol Neurosurg Psychiatry 2007;78:204–205.
11.
Hernández-Echebarría L, Saiz A, et al. Paraneoplastic encephalomyelitis associated with pancreatic tumor and anti-GAD antibodies. Neurology 2006;66:450–451.
12.
Bataller L, Valero C, Díaz R, et al. Cerebellar ataxia associated with neuroendocrine thymic carcinoma and GAD antibodies. J Neurol Neurosurg Psychiatry 2009;80:696–697.
13.
Graus F, Lang B, Pozo-Rosich P, Saiz A, Casamitjana R, Vincent A. P/Q type calcium-channel antibodies in paraneoplastic cerebellar degeneration with lung cancer. Neurology 2002;59:764–766.
14.
Alamowitch S, Graus F, Uchuya M, Reñé R, Bescansa E, Delattre JY. Limbic encephalitis and small cell lung cancer. Clinical and immunological features Brain 1997;120:923–928.
15.
Graus F, Boronat A, Xifró X, et al. The expanding clinical profile of anti-AMPA receptor encephalitis. Neurology 2010;74:857–859.
16.
Bataller L, Galiano R, García-Escrig M, et al. Reversible paraneoplastic limbic encephalitis associated with antibodies to the AMPA receptor. Neurology 2010;74:265–267.
17.
Sabater L, Titulaer M, Saiz A, Verschuuren J, Güre AO, Graus F. SOX1 antibodies are markers of paraneoplastic Lambert-Eaton myasthenic syndrome. Neurology 2008;70:924–928.
18.
Schuler V, Lüscher C, Blanchet C, et al. Epilepsy, hyperalgesia, impaired memory, and loss of pre- and postsynaptic GABA(B) responses in mice lacking GABA(B(1)). Neuron 2001;31:47–58.
19.
Gultekin SH, Rosenfeld MR, Voltz R, Eichen J, Posner JB, Dalmau J. Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients. Brain 2000;123:1481–494.
20.
Malter MP, Helmstaedter C, Urbach H, Vincent A, Bien CG. Antibodies to glutamic acid decarboxylase define a form of limbic encephalitis. Ann Neurol 2010;67:470–478.
21.
Ances BM, Vitaliani R, Taylor RA, et al. Treatment-responsive limbic encephalitis identified by neuropil antibodies: MRI and PET correlates. Brain 2005;128:1764–1777.
22.
Graus F, Keime-Guibert F, Reñe R, et al. Anti-Hu-associated paraneoplastic encephalomyelitis: analysis of 200 patients. Brain 2001;124:1138–1148.
23.
Niehusmann P, Dalmau J, Rudlowski C, et al. Diagnostic value of N-methyl-D-aspartate receptor antibodies in women with new-onset epilepsy. Arch Neurol 2009;66:458–464.
24.
Bettler B, Kaupmann K, Mosbacher J, Gassmann M. Molecular structure and physiological functions of GABA(B) receptors. Physiol Rev 2004;84:835–867.
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Copyright © 2011 by AAN Enterprises, Inc.
Publication History
Received: August 18, 2010
Accepted: November 12, 2010
Published online: February 28, 2011
Published in print: March 1, 2011
Disclosure
Dr. Boronat, Dr. Sabater, and Dr. Saiz report no disclosures. Dr. Dalmau has received royalties from a patent re: Ma2 autoantibody test and has patents pending re: NMDA and GABAB receptor autoantibody tests (license fee payments received from EUROIMMUN AG); and receives research support from funding from EUROIMMUN AG and the NIH/NCI. Dr. Graus serves on the editorial board of Lancet Neurology and has received research support from Fondo Investigaciones Santitarias.
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