ARTICLE
OPEN ACCESS
Autoimmune Global Amnesia as Manifestation of
AMPAR Encephalitis and Neuropathologic
Findings
Gerda Ricken, MSc, Tobias Zrzavy, MD, PhD, Stefan Macher, MD, Patrick Altmann, MD, PhD,
Johannes Troger, MD, Kim Kristin Falk, MD, Andreas Kiefer, MD, Andreas Fichtenbaum, PhD,
Goran Mitulovic, PhD, Helmut Kubista, PhD, Klaus-Peter Wandinger, MD, Paulus Rommer, MD,
Thorsten Bartsch, MD, Thomas Berger, MD, MSc, Jörg Weber, MD, PhD, Frank Leypoldt, MD, PhD,* and
Romana Höftberger, MD*
Correspondence
Dr. Höftberger
romana.hoeftberger@
meduniwien.ac.at
Neurol Neuroimmunol Neuroinflamm 2021;8:e1019. doi:10.1212/NXI.0000000000001019
Abstract
Objective
To report an unusual clinical phenotype of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
acid receptor (AMPAR) encephalitis and describe associated neuropathologic findings.
Methods
We retrospectively investigated 3 AMPAR encephalitis patients with autoimmune global
hippocampal amnesia using comprehensive cognitive and neuropsychologic assessment, antibody testing by in-house tissue-based and cell-based assays, and neuropathologic analysis of
brain autopsy tissue including histology and immunohistochemistry.
Results
Three patients presented with acute-to-subacute global amnesia without affection of cognitive
performance, attention, concentration, or verbal function. None of the patients had epileptic
seizures, change of behavior, personality changes, or psychiatric symptoms. The MRI was
normal in 1 patient and showed increased fluid-attenuated inversion recovery/T2 signal in the
hippocampus in the other 2 patients. Two patients showed complete remission after immunotherapy. The one patient who did not improve had an underlying adenocarcinoma of the
lung and died 3.5 months after disease onset because of tumor progression. Neuropathologic
analysis of the brain autopsy revealed unilateral hippocampal sclerosis accompanied by mild
inflammatory infiltrates, predominantly composed of T lymphocytes, and decrease of AMPAR
immunoreactivity.
Conclusion
AMPAR antibodies usually associate with limbic encephalitis but may also present with immune responsive, acute-to-subacute, isolated hippocampal dysfunction without overt inflammatory CSF or MRI changes.
*These authors contributed equally to this work.
From the Division of Neuropathology and Neurochemistry (G.R., A.F., R.H.), Department of Neurology, Medical University of Vienna, Austria; Department of Neurology (T.Z., S.M.,
P.A., P.R., T. Berger), Medical University of Vienna, Austria; Department of Neurology (J.T., J.W.), Klinikum Klagenfurt, Austria; Institute of Clinical Chemistry (K.K.F., K.-P.W., F.L.),
University Hospital Schleswig-Holstein, Kiel/Lübeck, Germany; Institute of Pathology (A.K.), Klinikum Klagenfurt, Austria; Clinical Department of Laboratory Medicine (A.F., G.M.),
Proteomics Core Facility, Medical University Vienna, Austria; Center of Physiology and Pharmacology (H.K.), Department of Neurophysiology and Neuropharmacology, Medical
University of Vienna, Austria; and Department of Neurology (T. Bartsch, F.L.), University Hospital Schleswig-Holstein, Kiel, Germany.
Funding information and disclosures are provided at the end of the article. Go to Neurology.org/nn for full disclosure forms.
The Article Processing Charge was funded by the Austrian Science Fund.
This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any
medium, provided the original work is properly cited.
Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
1
Glossary
AMPAR = alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; abs = antibodies; CBA = cell-based assays;
FLAIR = fluid-attenuated inversion recovery; HIER = heat-induced epitope retrieval; TGA = transient global amnesia.
Autoantibodies to the GluA1 and/or GluA2 subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) were originally identified in patients with
limbic encephalitis with prominent behavioral and psychiatric
changes and epileptic seizures.1 Up to 64% have an underlying
malignancy, most commonly thymoma, lung, or breast cancer.2-4
Subsequently, published studies expanded the spectrum of
neurologic deficits to focal weakness, involuntary movements,
autonomic dysfunction, upper motor neuron signs, apraxia,
aphasia, sensory symptoms, or ataxia as additional symptoms
apart from the limbic system.2,4 Recently, we identified AMPAR
antibodies (abs) in the CSF of a 31-year-old patient, who presented with a clinical picture reminiscent of transient global
amnesia without associated neurologic signs or overt inflammatory CSF or MRI changes and who readily responded to
immunotherapy. This observation and 2 subsequent patients
with similar phenotypes that came to our attention triggered this
study. Our aim was to describe this unusual and possibly overlooked clinical presentation of AMPAR encephalitis, we tentatively dubbed autoimmune global hippocampal amnesia, and to
present the associated neuropathologic findings in 1 patient who
died because of an underlying malignancy.
Methods
Patient Identification, Serum, and CSF Samples
All 3 patients were identified by screening accompanying clinical
descriptions of cases whose serum/CSF samples were sent for
diagnostic testing of antineuronal antibodies between 2016 and
2019 to participating laboratories in Lübeck, Kiel (Institute of
Clinical Chemistry, University Hospital Schleswig-Holstein,
Kiel/Lübeck) and Vienna (Division of Neuropathology and
Neurochemistry, Department of Neurology, Medical University
of Vienna). AMPAR abs were identified using an in-house tissuebased assay and in-house cell-based assays (CBA) transfected
with the GluA1 and GluA2 subunit of the AMPAR, as described
previously.2 All patients were personally examined by participating neurologists in Kiel, Vienna, or Klagenfurt.
Standard Protocol Approvals, Registrations,
and Patient Consents
This study was approved by the Ethics Committee of the
Medical University of Vienna (1,636/19 and 1,123/15),
Lübeck (13–162), and Kiel (B337-13).
Serum IgG Biotinylation and
Competition Assay
IgG was isolated from patients’ or healthy control sera with
protein A/G magnetic beads (88802, Thermo Fisher Scientific) and subsequently biotinylated with a sulfo-NHS2
biotinylation kit (21425, Thermo Fisher Scientific) according to manufacturer’s recommendations. These biotinylated
human IgG samples were then used for competition assays to
detect possible recognition of the same epitopes, as previously
reported.5 Briefly, rat brain sections were blocked and incubated with serum samples overnight at 4°C (dilution 1/5).
After washing, the sections were then incubated with biotinylated human IgG (serial dilutions from 1/2 to 1/10 in 5%
normal donkey serum) overnight at 4°C, and the reactivity
was developed with streptavidin-horseradish peroxidase solution followed by 3,3’-diaminobenzidin.
Neuropathology
Neuropathologic analysis was performed on formalin-fixed,
paraffin-embedded tissue sections of human brain autopsy
material. In total, 3–6 μm tissue sections were stained with
hematoxylin and eosin, and Luxol fast blue and nuclear fast
red staining. Immunohistochemistry was performed manually
in a humidified chamber for complement C9 neoantigen
(C9neo, polyclonal rabbit 1:2000, from Professor Paul Morgan, Cardiff, UK), GluA1 (AMPAR1, rabbit clone C3T 1:20;
Merck/Millipore), GluA2/3 (AMPAR2/3, polyclonal rabbit
1:200; Merck/Millipore), Granzyme B (GranB, mouse clone
GZB01 1:1,000; LabVision/Thermo Fisher Scientific),
GRIK2 (kainate receptor 2, polyclonal rabbit 1:500; SigmaAldrich), and human Leukocyte antigen (HLA) (mouse clone
HC10, 1:1,000, from Professor Hans Lassmann, Vienna,
Austria), using an avidin-biotin-complex method. Enzymatic
pretreatment with proteinase type 24 was used for C9neo
staining; heat-induced epitope retrieval with ethylenediaminetetraacetic acid buffer pH 9 was used for GluA1,
Granzyme B, and HLA-I stainings; and heat-induced epitope
retrieval with citrate buffer pH 6 was used for GluA2/3 and
GRIK2. Immunohistochemistry for the following primary
antibodies was performed on an automated platform Autostainer Link 48 and Envision FLEX + detection kit (Dako/
Agilent) and used according to manufacturer’s recommendations: alpha-synuclein (mouse clone 5G4 1:4,000; Analytik
Jena), beta-amyloid (mouse clone 6F/3D 1:100; Dako/
Agilent), CD3 (rabbit clone SP7 1:100; NeoMarkers/
Thermo Fisher Scientific), CD4 (mouse clone 4B12 1:100;
Dako/Agilent), CD8 (mouse clone C8/144B 1:100; Dako/
Agilent), CD20 (mouse clone L26 1:400; Dako/Agilent),
CD68 (mouse clone KP1 1:5,000; Dako/Agilent), CD79a
(mouse clone JCB117 1:100; Dako/Agilent), HLA-DR
(mouse clone CR3/43 1:400; Dako/Agilent), IgG (polyclonal rabbit 1:16,000; Dako/Agilent), CD45/leucocyte
common antigen (LCA; mouse clone 2B11+PD7/26 1:
2000; Dako/Agilent), Map2 (microtubule-associated protein2, mouse clone AP20 1:4,000; Merck/Millipore), pTDP-43
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(transactive response DNA-binding protein 43, phosphoSer409/410, mouse clone 11-9 1:20,000; Cosmo Bio), Tau
(phospho-Ser202/Thr205, mouse clone AT8 1:200; Thermo
Fisher Scientific), and TPPP/p25 (mouse clone 6C10 1:
2,000, from Professor Gabor Kovacs, Toronto, Canada).
Heat-induced epitope retrieval (HIER) with target-retrieval
solution low pH (Dako/Agilent) was used for pretreatment of
alpha-synuclein, CD8, CD20, CD68, CD79a, HLA-DR, IgG,
LCA, TDP-43, and TPPP/p25 staining, and target-retrieval
solution high pH (Dako/Agilent) was used for pretreatment
of CD3, CD4, and Map2 staining. Concentrated formic acid
pretreatment for 1 minute was used for alpha-synuclein and
pTDP-43 staining in addition to HIER. Approximately, 80%
formic acid (aqueous solution) for 1 hour was used for betaamyloid pretreatment. Tau staining needed no pretreatment.
Image acquisition was performed on a NanoZoomer 2.0-HT
digital slide scanner C9600 (Hamamatsu Photonics).
Data Availability
Anonymized data not published within this article will be
made available by request from any qualified investigator.
Results
We identified 3 patients (1 woman and 2 men; mean age at
symptom onset: 44 years; range 31–69 years) with a purely
amnestic syndrome and high titers of AMPAR abs demonstrated with brain immunohistochemistry and in-house cellbased assays (table). Two patients had antibodies in serum and
CSF (1 and 3), and 1 patient had antibodies only in CSF (2).
The clinical presentation in all 3 patients was characterized by
an acute-to-subacute onset of short episodes of poor recollection, evolving into complete global amnesia reminiscent of the
clinical syndrome known as transient global amnesia (median
time between first symptoms and full-fledged global amnesia
7.3 days, range 1–16 days). Comprehensive cognitive and
neuropsychological assessment revealed severe and isolated
deficits in visual short-term memory and auditory-verbal as well
as figural long-term memory and thus hippocampal dysfunction. Cognitive performance, attention, and concentration;
executive and verbal function; and visuoconstructive skills were
unaffected. None of the patients had epileptic seizures, change
of behavior, or psychiatric symptoms. While patient 1 had no
visible changes on MRI imaging, patient 2 showed uni- and
patient 3 bilateral increased fluid-attenuated inversion recovery
(FLAIR)/T2 signal in the hippocampus. EEG and CSF analyses were unremarkable. Two patients showed substantial
neurologic improvement after immunotherapy, 1 patient had a
relapse 4 months after the initial event that fully responded to
immunotherapy. One patient (3) had an adenocarcinoma of
the lung and only partially responded to immunotherapy. She
died 3.5 months after disease onset because of tumor
progression.
The antibodies of 3 patients recognized different epitopes of
the AMPAR, 2 labeled cells transfected with the GluA1
Neurology.org/NN
subunit, and 1 recognized cells transfected with the GluA2
subunit. Immune competition experiments demonstrated that
preincubation of tissue with serum of patient 3 (recognizing
GluA1 subunit) did not prevent the binding of a biotinylated
AMPAR serum (also recognizing the GluA1 subunit) derived
from a patient with classic symptoms of AMPAR encephalitis.
Neuropathologic analysis of the brain autopsy tissue of patient
3 revealed unilateral hippocampal sclerosis with subtotal loss
of neurons in the CA1 and CA4 sectors of the left hippocampus (figure 1, A and B) accompanied by microglial activation (figure 1, C and D); astrogliosis; and moderate
meningeal, perivascular, and parenchymal inflammatory infiltrates. The parenchymal inflammation was mainly composed of CD3/CD8+ T cells (figure 1, E–F). HLA Class I
antigen was upregulated in single neurons (figure 1G), some
of them with apposed CD8+/GranB + cytotoxic T cells
(figure 1, H and I). B cells and plasma cells were mainly
restricted to the meninges (figure 1, J and K). IgG deposits
were detectable in preserved CA1 neurons, the subiculum,
and occasionally in the isocortex. No deposits of complement
C9neo were visible (data not shown). In addition, we found
some perivascular inflammatory infiltrates in the basal ganglia,
dentate nucleus, and brainstem. Few parenchymal infiltrates
were visible in the formatio reticularis in the medulla oblongata. In addition, we found mild inflammatory infiltrates in the
parietal and occipital meninges. The neurons in the prefrontal
cortex and amygdala appeared well-preserved. No significant
neurodegeneration-associated protein aggregates were
detected; particularly, no pTDP-43, beta-amyloid, or alphasynuclein deposits were visible. We only identified single agerelated tau-positive neurofibrillary tangles, neuropil threads,
and isolated perivascular and subpial astrocytes. To determine
whether there was a decrease of expression of AMPAR, we
stained the hippocampus sections of our patient and 7 agematched controls (3 men and 4 women) without hippocampal pathology and 3 patients (1 man and 2 women) with
hippocampal sclerosis, with commercial anti-GluA1
(AMPAR1) and anti-GluA2/3 (AMPAR2/3) antibodies.
Compared with controls (figure 2, A and B), the expression of
AMPAR was substantially decreased in the patient’s hippocampal formation (bilateral) (figure 2, C and D), whereas the
number of synapses was not altered, as demonstrated with a
commercial kainate receptor antibody (figure 2, E and F).
Discussion
We report 3 patients with AMPAR encephalitis whose clinical
syndrome can be described as autoimmune global amnesia
characterized by an acute-to-subacute, global amnestic syndrome without seizures, behavioral, or psychiatric abnormalities that lasted for up to 3 weeks and completely resolved
after immunotherapy in the 2 cases without tumor. Acute
isolated amnesia as clinical presentation of AMPAR encephalitis has previously been described in a 92-year-old woman,
who remained stable after 6 cycles of IVIg.6 Although
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3
Table Summary of Patients’ Characteristics
Patients
1
2
3
Age, sex
31, male
32, male
69, female
Clinical syndrome
Subacute global amnesia
Subacute global amnesia
Acute global amnesia
First neurologic symptoms
Episodic short-lasting memory
dysfunction
Episodic memory dysfunction and
insomnia
Acute global amnesia
Time from onset to
global amnesia (d)
16
5
1
MRI changes
Absent
Unilateral mesiotemporal/
hippocampal FLAIR alteration
Bilateral hippocampal FLAIR/T2
alteration
CSF
Initially 6 WBC/μL, no oligoclonal bands
2 WBC/μL, no oligoclonal bands
4 WBC/μL, no oligoclonal bands
AMPAR abs titer
Serum: 1/800; CSF: 1/128
Serum: negative; CSF: 1/64
Serum: 1/1,600; CSF: 1/32
Tumor
Not detected
Not detected
Adenocarcinoma lung
Treatments
Iv steroids, rituximab
Initially Iv steroids, PLEX; after
3 wk rituximab
Iv steroids, PLEX, chemotherapy
Outcome and relapses
Complete resolution after steroids,
1 relapse leading to rituximab, and
no further symptoms
Response after steroids and
PLEX, complete resolution after
rituximab,
and no relapse
Partial response after PLEX and died
3.5 mo after onset because of tumor
progression
Follow-up
56 mo
46 mo
3.5 mo
Abbreviations: abs = antibodies; FLAIR/T2 = fluid-attenuated inversion recovery/T2-weighted imaging; PLEX = plasma exchange; WBC = white blood cells.
AMPARs are widely expressed in the brain, most patients with
AMPAR encephalitis present with neurologic deficits that are
restricted to the limbic system, including limbic encephalitis,
seizures, behavioral, and memory deficits. Whether this is
related to the density or composition of subunits of AMPARs
or brain-region-dependent variations of compensatory
mechanisms is unclear.7 AMPARs are heterotetrameric receptors composed of variable combinations of 4 subunits,
GluA1-4. Our data from in-house CBAs and immunocompetition studies do not suggest that the isolated amnestic
syndrome of our 3 patients is because of a specific receptor
subunit and confirm the epitope diversity within the receptor
that was described for AMPAR encephalitis.8
Amnestic syndrome refers to an impairment of memory and
can be classified as anterograde or retrograde. It can be observed after trauma, bleeding, ischemia, or inflammation (viral
or autoimmune, e.g., in limbic encephalitis associated with
adenylate kinase 5 antibodies9) and may be a symptom of a
psychiatric disorder (dissociative amnesia) or acute toxic
Figure 1 Neuropathologic Features of AMPAR Encephalitis
The left hippocampus shows hippocampal sclerosis with subtotal neuronal loss in the CA1 and CA4 sectors (A, rectangle enlarged in B; neuronal
marker Map2) accompanied by microglia activation (C and D, HLA-DR).
Parenchymal inflammatory infiltrates in the hippocampus are composed
of CD3+ (E) and CD8+ (F) T cells. Single neurons show an upregulation of
HLA Class I antigen (G). Some CD8+ (H) and Granzyme B+ (I) cytotoxic
T cells are shown in close apposition to neurons. B cells (J, CD20) and
plasma cells (K, CD79a) are mainly restricted to the meninges. Scale bars
in A and C: 200 μm. Scale bars in B, D–F, and J–K: 50 μm. Scale bars in G–I:
20 μm. AMPAR = alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
acid receptor.
4
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metabolic disorders.10,11 One of the most frequent forms is
transient global amnesia (TGA) that is characterized by
sudden onset of short-lasting (<24 hours) anterograde amnesia in the absence of other neurologic deficits.12-14 An impaired venous blood flow affecting hippocampal function
through congestive ischemia has been proposed as a possible
pathophysiologic mechanism.15 Shorter lasting episodes of
global amnesia over minutes to few hours can occur as epileptic syndrome (transient epileptic amnesia).16 In contrast to
TGA, the amnestic syndrome of our patients developed over a
period of 1 to 16 days and lasted for several weeks to months
although at the peak of disease patients were virtually indistinguishable from patients with TGA. In 1 patient (1) in
light of normal MRI and CSF without clear inflammatory
changes, a diagnosis of dissociative fugue was entertained.
However, the MRI showing an increased FLAIR/T2 signal in
the medial temporal lobes in the other 2 patients made the
final diagnosis more straightforward.
The encoding, consolidation, and retrieval of mnemonic information is critically dependent on a large bidirectional
network of brain areas that includes neocortical association
regions, subcortical nuclei, and the medial temporal lobe,
including the hippocampus. The hippocampus is a central
node in the memory network and the site of pathology in
many amnestic syndromes. Many intrahippocampal subnetworks are characterized by high densities of GluA1/2 and
GluA2/3 receptors.17 A particularly vulnerable area is the
CA1 sector, which is highly sensitive to hypoxia of diverse
toxic or metabolic conditions, such as hypoglycemia or abuse
of psychostimulant drugs.18 Neuropathologic investigation of
the brain in our patient revealed unilateral hippocampal
sclerosis affecting the CA1 and CA4 regions of the hippocampus. The contralateral hippocampus and other areas involved in memory, such as prefrontal cortex, cingulum, or
thalamus, did not show significant neuronal loss or inflammation. However, we found IgG deposition and a decrease of AMPAR immunoreactivity that was most
pronounced in the hippocampal formation on both sides
and not associated with a decrease of synaptic density or
complement deposition. These findings are in line with
previous studies that demonstrated a decrease of synaptic
clusters of AMPAR subunits through antibody-mediated
internalization.1,19,20 Whether hippocampal sclerosis in our
patient is a result of the pathogenic effects of the AMPAR
antibodies on synaptic function in highly vulnerable regions
or secondary to a T-cell-mediated mechanism possibly
triggered by a tumor-associated breach of tolerance is unclear. A hypoxic damage of the hippocampal neurons was
ruled out because the patient was not affected by hypoxicischemic events before death.
The cases reported here have important clinical implications:
AMPAR encephalitis may present with an acute/subacute
global amnestic syndrome, sometimes with normal MRI that
is potentially reversible with immunotherapy. The pathologic
substrate of this syndrome seems to be a predominant inflammatory involvement of the CA1 and CA4 regions of the
hippocampus accompanied by a decrease of expression of
AMPARs.
Figure 2 Decrease of AMPAR Density in Human Hippocampus In Vivo
Compared with a control hippocampus (A, rectangle enlarged in B; GluA1),
the hippocampus of the AMPAR encephalitis patient shows a significantly
reduced AMPAR immunoreactivity (C, rectangle enlarged in D; GluA1),
whereas the synaptic density is not altered (E, rectangle enlarged in F;
GRIK2). Scale bars in A, C, and E: 1 mm. Scale bars in B, D, and F: 50 μm.
AMPAR = alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
receptor.
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Neurology: Neuroimmunology & Neuroinflammation | Volume 8, Number 4 | July 2021
5
Acknowledgment
The authors thank Prof. J. Dalmau (University of Barcelona,
Spain) and Prof. E. Gelpi (Medical University of Vienna,
Austria) for helpful comments, Prof. J. Dalmau for support in
antibody testing, and Ulrike Köck (Medical University of
Vienna, Austria) for her excellent technical support.
Name
(continued)
Location
Contribution
Tobias Zrzavy, Medical University of
MD, PhD
Vienna, Austria
Acquisition of data, execution,
and critical review for
important intellectual content
Stefan
Macher, MD
Medical University of
Vienna, Austria
Acquisition of data,
interpretation of data, and
critical review for important
intellectual content
Patrick
Altmann, MD,
PhD
Medical University of
Vienna, Austria
Acquisition of data, execution,
and critical review for
important intellectual content
Johannes
Troger, MD
Klinikum Klagenfurt,
Austria
Acquisition of data, execution,
and critical review for
important intellectual
content
Kim Kristin
Falk, MD
University Hospital
Schleswig-Holstein, Kiel/
Lübeck, Germany
Acquisition of data, execution,
and critical review for
important intellectual
content
Andreas
Kiefer, MD
Klinikum Klagenfurt,
Austria
Acquisition of data and critical
review for important
intellectual content
Andreas
Fichtenbaum,
PhD
Medical University of
Vienna, Austria
Acquisition of data, execution,
interpretation of data, and
critical review for important
intellectual content
Goran
Mitulovic,
PhD
Medical University of
Vienna, Austria
Acquisition of data and critical
review for important
intellectual content
Helmut
Kubista, PhD
Medical University of
Vienna, Austria
Acquisition of data and
critical review for
important intellectual
content
Klaus-Peter
Wandinger,
MD
University Hospital
Schleswig-Holstein, Kiel/
Lübeck, Germany
Interpretation of data and
critical review for
important intellectual
content
Paulus
Rommer, MD
Medical University of
Vienna, Austria
Interpretation of data and
critical review for important
intellectual content
Thorsten
Bartsch, MD
University Hospital
Schleswig-Holstein, Kiel,
Germany
Interpretation of data and
critical review for
important intellectual
content
Thomas
Berger, MD,
MSc
Medical University of
Vienna, Austria
Interpretation of data and
critical review for important
intellectual content
Received by Neurology: Neuroimmunology & Neuroinflammation
February 8, 2021. Accepted in final form March 23, 2021.
Jörg Weber,
MD, PhD
Klinikum Klagenfurt,
Austria
Acquisition of data,
interpretation of data,
and critical review for
important intellectual
content
Appendix Authors
Frank
Leypoldt, MD,
PhD
University Hospital
Schleswig-Holstein, Kiel/
Lübeck, Germany
Conception and design,
acquisition of data, execution,
interpretation of data, and
critical review for important
intellectual content
Romana
Höftberger,
MD
Medical University of
Vienna, Austria
Conception and design,
acquisition of data, execution,
interpretation of data, and
critical review for important
intellectual content
Study funding
This work was partly supported by grants from the
“Jubiläumsfonds der Österreichischen Nationalbank,” project
16919 (RH), Austrian Science Fund FWF, SYNABS (RH)
and DOC 33-B27 (RH), and the German Ministry of Education and Research (BMBF, 01 GM1908A) (FL).
Disclosure
G. Ricken, T. Zrzavy, S. Macher, P. Altmann, J. Troger, K.K. Falk,
A. Kiefer, A. Fichtenbaum, G. Mitulovic, H. Kubista, K.-P.
Wandinger, P. Rommer, T. Bartsch, and J. Weber report no
disclosures. T. Berger has participated in meetings sponsored by
and received honoraria (lectures, advisory boards, and consultations) from pharmaceutical companies marketing treatments
for MS: Allergan, Biogen, Biologix, Bionorica, Celgene, Eisei,
MedDay, Merck, Novartis, Roche, Sanofi-Genzyme, Teva, and
UCB. His institution has received financial support in the past 12
months by unrestricted research grants (Bayer, Biogen, Merck,
Novartis, Roche, Sanofi-Genzyme, and Teva) and for participation in clinical trials in multiple sclerosis sponsored by Alexion,
Bayer, Biogen, Merck, Novartis, Roche, Sanofi-Aventis, and
Teva; Frank Leypoldt reports speakers honoraria from Grifols,
Teva, Biogen, Roche, Alexion, Merck, Bayer, and Fresenius and
advisory board memberships for Roche, Alexion, and Biogen
outside of this work. He receives grants from the German
Ministry of Education and Research (BMBF, 01 GM1908A) and
the German Research Council (E-Rare Joint Transnational
(ERA-Net) Transnational research call LE3064/2-1). He works
for an academic institution that offers commercial antibody
testing. R. Höftberger reports speaker’s honoraria from Novartis
and Biogen. The Medical University of Vienna (Austria; employer of Dr. Höftberger) receives payment for antibody assays
and for antibody validation experiments organized by Euroimmun (Lübeck, Germany). Go to Neurology.org/nn for full
disclosure forms.
Publication History
6
Appendix
Name
Location
Contribution
Gerda Ricken,
MSc
Medical University of
Vienna, Austria
Conception and design,
acquisition of data, statistical
analysis, execution,
interpretation of data, and
critical review for
important intellectual
content
Neurology: Neuroimmunology & Neuroinflammation | Volume 8, Number 4 | July 2021
Neurology.org/NN
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Neurology: Neuroimmunology & Neuroinflammation | Volume 8, Number 4 | July 2021
7
Autoimmune Global Amnesia as Manifestation of AMPAR Encephalitis and
Neuropathologic Findings
Gerda Ricken, Tobias Zrzavy, Stefan Macher, et al.
Neurol Neuroimmunol Neuroinflamm 2021;8;
DOI 10.1212/NXI.0000000000001019
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