Antibodies to the GABAB receptor in limbic encephalitis with seizures: Case series and characterisation of the antigen

被引：868

作者：

Lancaster, Eric

Lai, Meizan

Peng, Xiaoyu ^{[2
]}

Hughes, Ethan ^{[2
]}

Constantinescu, Radu ^{[4
]}

Raizer, Jeffrey ^{[5
]}

Friedman, Daniel ^{[6
]}

Skeen, Mark B. ^{[7
]}

Grisold, Wolfgang ^{[8
]}

Kimura, Akio ^{[9
]}

Ohta, Kouichi ^{[10
]}

Iizuka, Takahiro ^{[11
]}

Guzman, Miguel ^{[3
]}

Graus, Francesc ^{[12
,13
]}

Moss, Stephen J. ^{[14
]}

Balice-Gordon, Rita ^{[2
]}

Dalmau, Josep ^{[1
]}

机构：

[1] Univ Penn, Div Neurooncol, Dept Neurol, Sch Med, Philadelphia, PA 19104 USA

[2] Univ Penn, Dept Neurosci, Sch Med, Philadelphia, PA 19104 USA

[3] Univ Penn, Div Anat Pathol, Sch Med, Philadelphia, PA 19104 USA

[4] Sahlgrens Univ Hosp, Dept Neurol, Gothenburg, Sweden

[5] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA

[6] Columbia Univ, Comprehens Epilepsy Ctr, Med Ctr, New York, NY USA

[7] Duke Univ, Med Ctr, Div Neurol, Dept Med, Durham, NC 27710 USA

[8] Kaiser Franz Josef Hosp, Dept Neurol, Vienna, Austria

[9] Gifu Univ, Dept Neurol & Geriatr, Grad Sch Med, Gifu, Japan

[10] Tachikawa Hosp, Dept Neurol, Tokyo, Japan

[11] Kitasato Univ, Sch Med, Dept Neurol, Sagamihara, Kanagawa 228, Japan

[12] Hosp Clin Barcelona, Serv Neurol, Barcelona, Spain

[13] IDIBAPS, Barcelona, Spain

[14] Tufts Univ, Sch Med, Dept Neurosci, Boston, MA 02111 USA

来源：

LANCET NEUROLOGY | 2010年 / 9卷 / 01期

基金：

美国国家卫生研究院;

关键词：

SYNAPTIC PLASTICITY; NMDAR ENCEPHALITIS; GLOBUS-PALLIDUS; TRAFFICKING; EPILEPSY; TISSUE; MICE; RESPONSES; BACLOFEN; CHANNELS;

D O I：

10.1016/S1474-4422(09)70324-2

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

100204 [神经病学];

摘要：

Background Some encephalitides or seizure disorders once thought idiopathic now seem to be immune mediated. We aimed to describe the clinical features of one such disorder and to identify the autoantigen involved. Methods 15 patients who were suspected to have paraneoplastic or immune-mediated limbic encephalitis were clinically assessed. Confocal microscopy, immunoprecipitation, and mass spectrometry were used to characterise the autoantigen. An assay of HEK293 cells transfected with rodent GABA(B1) or GABA(B2) receptor subunits was used as a serological test. 91 patients with encephalitis suspected to be paraneoplastic or immune mediated and 13 individuals with syndromes associated with antibodies to glutamic acid decarboxylase 65 were used as controls. Findings All patients presented with early or prominent seizures; other symptoms, MRI, and electroencephalography findings were consistent with predominant limbic: dysfunction. All patients had antibodies (mainly IgG1) against a neuronal cell-surface antigen; in three patients antibodies were detected only in CSF. Immunoprecipitation and mass spectrometry showed that the antibodies recognise the B1 subunit of the GABA(B) receptor, an inhibitory receptor that has been associated with seizures and memory dysfunction when disrupted. Confocal microscopy showed colocalisation of the antibody with GABA(B) receptors. Seven of 15 patients had tumours, five of which were small-cell lung cancer, and seven patients had non-neuronal autoantibodies. Although nine of ten patients who received immunotherapy and cancer treatment (when a tumour was found) showed neurological improvement, none of the four patients who were not similarly treated improved (p=0.005). Low levels of GABA(B1) receptor antibodies were identified in two of 104 controls (p<0.0001). Interpretation GABA(B) receptor autoimmune encephalitis is a potentially treatable disorder characterised by seizures and, in some patients, associated with small-cell lung cancer and with other autoantibodies.

引用

页码：67 / 76

页数：10

共 40 条

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