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@ARTICLE{Widman:824547,
author = {Widman, Guido and Golombeck, Kristin and Hautzel, Hubertus
and Gross, Catharina C. and Quesada, Carlos M. and Witt,
Juri-Alexander and Rota Kops, Elena and Ermert, Johannes and
Greschus, Susanne and Surges, Rainer and Helmstaedter,
Christoph and Wiendl, Heinz and Melzer, Nico and Elger,
Christian E.},
title = {{T}reating a {GAD}65 {A}ntibody-{A}ssociated {L}imbic
{E}ncephalitis with {B}asiliximab: {A} {C}ase {S}tudy},
journal = {Frontiers in neurology},
volume = {6},
issn = {1664-2295},
address = {Lausanne},
publisher = {Frontiers Research Foundation},
reportid = {FZJ-2016-07119},
pages = {167},
year = {2015},
abstract = {Background: Antibodies (ABs) against the 65-kDa isoform of
the intracellular enzymeglutamate decarboxylase (GAD65) have
been found in limbic encephalitis (LE) andother neurological
conditions. The direct significance of anti-GAD65-ABs for
epilepsyis unclear. However, in histological preparations
from biopsies of resective epilepsysurgeries, predominantly
cytotoxic T-lymphocytes were detected making close
contactsto neurons. Activated T-lymphocytes can, in turn, be
selectively controlled by therapeuticinterleukin-2 receptor
Abs, such as basiliximab.Case presentation: We report of a
25-year-old male patient with epilepsy since theage of 18
and displaying clinical signs of LE and a high titer of
GAD65 ABs in cerebro-spinal fluid (CSF) and serum. Monthly,
repetitive, intravenous cortisone pulse therapiesthat were
initially administered for 6 months failed to improve his
condition. Subsequentflow-cytometry analysis of CSF showed
especially an increased fraction of
activatedHLA-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/monthwas
started. After 3 months, the fCD8+TL in the CSF normalized;
after 6 months, thepsychological impulse-control deficits
normalized; and after 11 months the patientwas seizure free.
However, 7 weeks later, seizures and, later on,
psychological deficitsrecurred and fCD8+TL was once again
present in the CSF. Flumazenil PET, magneticresonance
imaging-volumetry, and neuropsychological changes during
therapy aredescribed.Conclusion: The correlation of the
fCD8+TL in the CSF with clinical and paraclinical measures
of disease activity combined with the unambiguous response
to basiliximabstrongly 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 ofhuman anti-drug ABs, a well-known
complication of therapy with chimeric ABs.},
cin = {KME / INM-4 / INM-5},
ddc = {610},
cid = {I:(DE-Juel1)VDB145 / I:(DE-Juel1)INM-4-20090406 /
I:(DE-Juel1)INM-5-20090406},
pnm = {572 - (Dys-)function and Plasticity (POF3-572)},
pid = {G:(DE-HGF)POF3-572},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000363857200001},
pubmed = {pmid:26284025},
doi = {10.3389/fneur.2015.00167},
url = {https://juser.fz-juelich.de/record/824547},
}