Encephalitis and GABAB receptor antibodies: novel findings in a new case series of 20 patients.
OBJECTIVE
To report the clinical features of 20 newly diagnosed patients with GABAB receptor (GABABR) antibodies and determine the frequency of associated tumors and concurrent neuronal autoantibodies.


METHODS
Clinical data were retrospectively obtained and evaluated. Serum and CSF samples were examined for additional antibodies using methods previously reported.


RESULTS
Seventeen patients presented with seizures, memory loss, and confusion, compatible with limbic encephalitis (LE), one patient presented with ataxia, one patient presented with status epilepticus, and one patient presented with opsoclonus-myoclonus syndrome (OMS). Nineteen (95%) patients eventually developed LE during the course of the disease. Small-cell lung cancer (SCLC) was identified in 10 (50%) patients, all with LE. Treatment and outcome was available from 19 patients: 15 showed complete (n = 7) or partial (n = 8) neurologic improvement after steroids, IV immunoglobulins, or plasma exchange and oncologic treatment when indicated; 1 patient died of tumor progression shortly after the first cycle of immunotherapy, and 3 were not treated. Five patients with SCLC had additional onconeuronal antibodies (Ri, amphiphysin, or SOX1), and 2 without tumor had GAD65 and NMDAR antibodies, respectively. GABABR antibodies were not detected in serum of 116 patients with SCLC without neurologic symptoms.


CONCLUSIONS
Our study confirms GABABR as an autoantigen of paraneoplastic and nonparaneoplastic LE and expands the phenotype of GABABR antibodies to ataxia, OMS, and status epilepticus. The long-term prognosis is dictated by the presence of a tumor. Recognition of syndromes associated with GABABR antibodies is important because they usually respond to treatment.
From the Service of Neurology (R.H., M.T., L.S., A.S., F.G.), Hospital Clínic, Universitat de Barcelona and Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Institute of Neurology (R.H.), Medical University of Vienna, Austria; Department of Neurology (M.T.), Erasmus Medical Center, Rotterdam, the Netherlands; Department of Tumor Biology (B.D., A.R., B.H., M.A.H., V.L.), National Koranyi Institute of TB and Pulmonology, Budapest, Hungary; Department of Thoracic Surgery (B.D., A.R., B.H., M.A.H., V.L., H.J.A.), Medical University of Vienna, Austria; 2nd Department of Pathology (B.H.), Semmelweis University, Budapest, Hungary; Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration (H.J.A.), Vienna, Austria; Department of Neurology (L.H.), Charité University Medicine Berlin, Germany; Servicio Neurología (S.B.), Hospital de Cruces, Barakaldo; Servicio Neurología (A.d.F.), Hospital Ramón y Cajal, Madrid; Institució Catalana de Recerca i Estudis Avançats (ICREA) (J.D.), IDIBAPS, Hospital Clínic, Barcelona, Spain; and Department of Neurology (J.D.), University of Pennsylvania, Philadelphia.
Romana
R
Höftberger
Maarten J
MJ
Titulaer
Lidia
L
Sabater
Balazs
B
Dome
Anita
A
Rózsás
Balazs
B
Hegedus
Mir Alireza
MA
Hoda
Viktoria
V
Laszlo
Hendrik Jan
HJ
Ankersmit
Lutz
L
Harms
Sabas
S
Boyero
Alicia
A
de Felipe
Albert
A
Saiz
Josep
J
Dalmau
Francesc
F
Graus
D000293:Adolescent; D000328:Adult; D000368:Aged; D001259:Ataxia / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology; D001323:Autoantibodies / Q000096:biosynthesis* / Q000097:blood / Q000134:cerebrospinal fluid; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D020363:Limbic Encephalitis / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D008175:Lung Neoplasms / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D053578:Opsoclonus-Myoclonus Syndrome / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology; D011379:Prognosis; D018080:Receptors, GABA-B / Q000276:immunology*; D012189:Retrospective Studies; D055752:Small Cell Lung Carcinoma / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D013226:Status Epilepticus / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology; D055815:Young Adult
D001323:Autoantibodies; D018080:Receptors, GABA-B