PMID- 32246252
OWN - NLM
STAT- MEDLINE
DCOM- 20210412
LR  - 20210710
IS  - 1432-1459 (Electronic)
IS  - 0340-5354 (Print)
IS  - 0340-5354 (Linking)
VI  - 267
IP  - 7
DP  - 2020 Jul
TI  - Routine diagnostics for neural antibodies, clinical correlates, treatment and 
      functional outcome.
PG  - 2101-2114
LID - 10.1007/s00415-020-09814-3 [doi]
AB  - OBJECTIVE: To determine frequencies, interlaboratory reproducibility, clinical 
      ratings, and prognostic implications of neural antibodies in a routine laboratory 
      setting in patients with suspected neuropsychiatric autoimmune conditions. 
      METHODS: Earliest available samples from 10,919 patients were tested for a broad 
      panel of neural antibodies. Sera that reacted with leucine-rich 
      glioma-inactivated protein 1 (LGI1), contactin-associated protein-2 (CASPR2), or 
      the voltage-gated potassium channel (VGKC) complex were retested for LGI1 and 
      CASPR2 antibodies by another laboratory. Physicians in charge of patients with 
      positive antibody results retrospectively reported on clinical, treatment, and 
      outcome parameters. RESULTS: Positive results were obtained for 576 patients 
      (5.3%). Median disease duration was 6 months (interquartile range 0.6-46 months). 
      In most patients, antibodies were detected both in CSF and serum. However, in 16 
      (28%) patients with N-methyl-D-aspartate receptor (NMDAR) antibodies, this 
      diagnosis could be made only in cerebrospinal fluid (CSF). The two laboratories 
      agreed largely on LGI1 and CASPR2 antibody diagnoses (kappa = 0.95). The clinicians 
      (413 responses, 71.7%) rated two-thirds of the antibody-positive patients as 
      autoimmune. Antibodies against the 
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), NMDAR (CSF 
      or high serum titer), gamma-aminobutyric acid-B receptor (GABABR), and LGI1 had >/= 90% 
      positive ratings, whereas antibodies against the glycine receptor, VGKC complex, 
      or otherwise unspecified neuropil had </= 40% positive ratings. Of the patients 
      with surface antibodies, 64% improved after >/= 3 months, mostly with >/= 1 
      immunotherapy intervention. CONCLUSIONS: This novel approach starting from 
      routine diagnostics in a dedicated laboratory provides reliable and useful 
      results with therapeutic implications. Counseling should consider clinical 
      presentation, demographic features, and antibody titers of the individual 
      patient.
FAU - Bien, Christian G
AU  - Bien CG
AUID- ORCID: 0000-0003-2225-8654
AD  - Epilepsy Center Bethel, Krankenhaus Mara, Maraweg 17-21, 33617, Bielefeld, 
      Germany. christian.bien@gmx.de.
FAU - Bien, Corinna I
AU  - Bien CI
AD  - Laboratory Krone, Bad Salzuflen, Germany.
FAU - Dogan Onugoren, Mujgan
AU  - Dogan Onugoren M
AD  - Department of Neurology, Epilepsy Center, Friedrich-Alexander-Universitat, 
      Erlangen-Nurnberg, Germany.
FAU - De Simoni, Desiree
AU  - De Simoni D
AUID- ORCID: 0000-0003-3705-8903
AD  - Division of Neuropathology and Neurochemistry, Department of Neurology, Medical 
      University of Vienna, Vienna, Austria.
AD  - Department of Neurology, University Hospital St. Poelten, St. Poelten, Austria.
FAU - Eigler, Verena
AU  - Eigler V
AD  - Department of Neurology, Stadtisches Klinikum Ludwigshafen Am Rhein, 
      Ludwigshafen, Germany.
FAU - Haensch, Carl-Albrecht
AU  - Haensch CA
AUID- ORCID: 0000-0001-6479-0265
AD  - Department of Neurology, Kliniken Maria Hilf Moenchengladbach, Faculty of Health, 
      University of Witten/Herdecke, Moenchengladbach, Germany.
FAU - Holtkamp, Martin
AU  - Holtkamp M
AD  - Epilepsy-Center Berlin-Brandenburg, Institute for Diagnostics of Epilepsy, 
      Evangelisches Krankenhaus Konigin Elisabeth Herzberge, Berlin, Germany.
FAU - Ismail, Fatme S
AU  - Ismail FS
AUID- ORCID: 0000-0003-3930-8056
AD  - Department of Neurology, University Hospital Bochum, Knappschaftskrankenhaus, 
      Bochum, Germany.
FAU - Kurthen, Martin
AU  - Kurthen M
AD  - Swiss Epilepsy Center, Zurich, Switzerland.
FAU - Melzer, Nico
AU  - Melzer N
AD  - Department of Neurology with Institute of Translational Neurology, University 
      Hospital Munster, Munster, Germany.
FAU - Mayer, Kristina
AU  - Mayer K
AD  - Department of Neurology, University Hospital of Augsburg, Augsburg, Germany.
FAU - von Podewils, Felix
AU  - von Podewils F
AUID- ORCID: 0000-0002-3134-8697
AD  - Department of Neurology, University Medicine Greifswald, Greifswald, Germany.
FAU - Rauschka, Helmut
AU  - Rauschka H
AD  - Department of Neurology and Karl Landsteiner Institute for Neuroimmunological and 
      Neurodegenerative Disorders, Sozialmedizinisches Zentrum Ost, Donauspital, 
      Vienna, Austria.
FAU - Rossetti, Andrea O
AU  - Rossetti AO
AUID- ORCID: 0000-0002-7878-172X
AD  - Department of Clinical Neurosciences, University Hospital (CHUV) and University 
      of Lausanne, Lausanne, Switzerland.
FAU - Schabitz, Wolf-Rudiger
AU  - Schabitz WR
AD  - Department of Neurology, EvKB-Bethel, Bielefeld, Germany.
FAU - Simova, Olga
AU  - Simova O
AD  - Protestant Hospital Alsterdorf, Epilepsy Center Hamburg, Hamburg, Germany.
FAU - Witt, Karsten
AU  - Witt K
AD  - Department of Neurology and Research Centre of Neurosensory Sciences, Carl Von 
      Ossietzky University, Oldenburg, Germany.
FAU - Hoftberger, Romana
AU  - Hoftberger R
AUID- ORCID: 0000-0002-5769-1100
AD  - Division of Neuropathology and Neurochemistry, Department of Neurology, Medical 
      University of Vienna, Vienna, Austria.
FAU - May, Theodor W
AU  - May TW
AUID- ORCID: 0000-0001-6517-9425
AD  - Society of Epilepsy Research, Bielefeld, Germany.
LA  - eng
PT  - Journal Article
DEP - 20200403
PL  - Germany
TA  - J Neurol
JT  - Journal of neurology
JID - 0423161
RN  - 0 (Autoantibodies)
RN  - 0 (CNTNAP2 protein, human)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (LGI1 protein, human)
RN  - 0 (Membrane Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Potassium Channels, Voltage-Gated)
RN  - 0 (Receptors, AMPA)
RN  - 0 (Receptors, GABA-B)
RN  - 0 (Receptors, Glycine)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - EC 4.1.1.15 (Glutamate Decarboxylase)
RN  - EC 4.1.1.15 (glutamate decarboxylase 2)
SB  - IM
EIN - J Neurol. 2020 May 12;:. PMID: 32399693
EIN - J Neurol. 2021 Aug;268(8):3056-3057. PMID: 34170405
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - *Autoantibodies/analysis/blood/cerebrospinal fluid
MH  - Autoimmune Diseases of the Nervous System/blood/cerebrospinal 
      fluid/*diagnosis/immunology
MH  - Child
MH  - Child, Preschool
MH  - Diagnostic Techniques, Neurological/*standards
MH  - Female
MH  - Glutamate Decarboxylase/*immunology
MH  - HEK293 Cells
MH  - Humans
MH  - Immunologic Tests/*standards
MH  - Infant
MH  - Intracellular Signaling Peptides and Proteins/*immunology
MH  - Male
MH  - Membrane Proteins/*immunology
MH  - Mental Disorders/blood/cerebrospinal fluid/*diagnosis/immunology
MH  - Middle Aged
MH  - Nerve Tissue Proteins/*immunology
MH  - Neuropil/*immunology
MH  - Potassium Channels, Voltage-Gated/*immunology
MH  - Receptors, AMPA/*immunology
MH  - Receptors, GABA-B/*immunology
MH  - Receptors, Glycine/*immunology
MH  - Receptors, N-Methyl-D-Aspartate/*immunology
MH  - Reproducibility of Results
MH  - Retrospective Studies
MH  - Young Adult
PMC - PMC8213550
OTO - NOTNLM
OT  - Autoimmune encephalitis
OT  - Immunotherapy
OT  - Laboratory test evaluation
OT  - Neural autoantibodies
OT  - Outcome
COIS- Dr. CG Bien obtained honoraria for speaking engagements from UCB, Desitin 
      (Hamburg, Germany), and Euroimmun. He receives research support from Deutsche 
      Forschungsgemeinschaft (German Research Council, Bonn, Germany) and 
      Gerd-Altenhof-Stiftung (Deutsches Stiftungszentrum, Essen, Germany). Dr. M 
      Holtkamp obtained speaker's honoraria and/or consultancy fees from Arvelle, Bial, 
      Desitin, Eisai, GW Pharmaceuticals, Novartis, and UCB. Dr. N Melzer has received 
      honoraria for lecturing and travel expenses for attending meetings from Biogen 
      Idec, GlaxoSmith Kline, Teva, Novartis Pharma, Bayer Healthcare, Genzyme, Alexion 
      Pharmaceuticals, Fresenius Medical Care, Diamed, and BIAL, and has received 
      financial research support from Euroimmun, Fresenius Medical Care, Diamed, 
      Alexion Pharmaceuticals, and Novartis Pharma. Dr. F von Podewils obtained 
      honoraria for speaking engagements from UCB, Eisai, and BIAL. Dr H Rauschka 
      obtained honoraria for speaking engagements, consulting, serving on advisory 
      boards and funding for conference travels from Biogen, Merck, Novartis, Roche, 
      Sanofi and Teva-Ratiopharm. Dr. R Hoftberger obtained honoraria for speaking 
      engagements from Euroimmun and Novartis. She receives research support from the 
      Jubilaumsfonds der Osterreichischen Nationalbank, Project 16919, and the GBS/CIDP 
      Foundation International. The Medical University of Vienna receives payments for 
      antibody assays. The other authors report no conflicts of interest.
EDAT- 2020/04/05 06:00
MHDA- 2021/04/13 06:00
PMCR- 2020/04/03
CRDT- 2020/04/05 06:00
PHST- 2020/02/13 00:00 [received]
PHST- 2020/03/28 00:00 [accepted]
PHST- 2020/03/28 00:00 [revised]
PHST- 2020/04/05 06:00 [pubmed]
PHST- 2021/04/13 06:00 [medline]
PHST- 2020/04/05 06:00 [entrez]
PHST- 2020/04/03 00:00 [pmc-release]
AID - 10.1007/s00415-020-09814-3 [pii]
AID - 9814 [pii]
AID - 10.1007/s00415-020-09814-3 [doi]
PST - ppublish
SO  - J Neurol. 2020 Jul;267(7):2101-2114. doi: 10.1007/s00415-020-09814-3. Epub 2020 
      Apr 3.