Treating a GAD65 Antibody-Associated Limbic Encephalitis with Basiliximab: A Case Study.
BACKGROUND
Antibodies (ABs) against the 65-kDa isoform of the intracellular enzyme glutamate decarboxylase (GAD65) have been found in limbic encephalitis (LE) and other neurological conditions. The direct significance of anti-GAD65-ABs for epilepsy is unclear. However, in histological preparations from biopsies of resective epilepsy surgeries, predominantly cytotoxic T-lymphocytes were detected making close contacts to neurons. Activated T-lymphocytes can, in turn, be selectively controlled by therapeutic interleukin-2 receptor Abs, such as basiliximab.


METHODS
We report of a 25-year-old male patient with epilepsy since the age of 18 and displaying clinical signs of LE and a high titer of GAD65 ABs in cerebrospinal fluid (CSF) and serum. Monthly, repetitive, intravenous cortisone pulse therapies that were initially administered for 6 months failed to improve his condition. Subsequent flow-cytometry analysis of CSF showed especially an increased fraction of activated HLA-DR(+) CD8(+) T-lymphocytes (fCD8(+)TL) when compared to controls. Thus, a second, intravenous cortisone pulse therapy with an additional basiliximab dose of 20 mg/month was started. After 3 months, the fCD8(+)TL in the CSF normalized; after 6 months, the psychological impulse-control deficits normalized; and after 11 months the patient was seizure free. However, 7 weeks later, seizures and, later on, psychological deficits recurred and fCD8(+)TL was once again present in the CSF. Flumazenil PET, magnetic resonance imaging-volumetry, and neuropsychological changes during therapy are described.


CONCLUSIONS
The correlation of the fCD8(+)TL in the CSF with clinical and paraclinical measures of disease activity combined with the unambiguous response to basiliximab strongly argues in favor of the putative pathogenic role fCD8(+)TL in anti-GAD65 LE. The clinical relapse at the end of the observation period might be due to the formation of human anti-drug ABs, a well-known complication of therapy with chimeric ABs.
Department of Epileptology, University of Bonn , Bonn , Germany.
Guido
G
Widman
Department of Neurology, University of Münster , Münster , Germany.
Kristin
K
Golombeck
Department of Nuclear Medicine (KME), Medical Faculty, Research Center Jülich, Heinrich-Heine-University Düsseldorf , Jülich , Germany.
Hubertus
H
Hautzel
Department of Neurology, University of Münster , Münster , Germany.
Catharina C
CC
Gross
Department of Epileptology, University of Bonn , Bonn , Germany.
Carlos M
CM
Quesada
Department of Epileptology, University of Bonn , Bonn , Germany.
Juri-Alexander
JA
Witt
Department of "Neurowissenschaften und Medizin" 4 (INM-4), Research Center Jülich , Jülich , Germany.
Elena
E
Rota-Kops
Department of "Neurowissenschaften und Medizin" 4 (INM-4), Research Center Jülich , Jülich , Germany.
Johannes
J
Ermert
Department of Radiology, University of Bonn , Bonn , Germany.
Susanne
S
Greschus
Department of Epileptology, University of Bonn , Bonn , Germany.
Rainer
R
Surges
Department of Epileptology, University of Bonn , Bonn , Germany.
Christoph
C
Helmstaedter
Department of Neurology, University of Münster , Münster , Germany.
Heinz
H
Wiendl
Department of Neurology, University of Münster , Münster , Germany.
Nico
N
Melzer
Department of Epileptology, University of Bonn , Bonn , Germany.
Christian E
CE
Elger
GAD65; basiliximab; cytotoxic T lymphocytes; epilepsy; limbic encephalitis