Publications by authors named "Klaus-Peter Wandinger"

73 Publications

The temporal course of T- and B-cell-responses to vaccination with BNT162b2 and mRNA-1273.

Clin Microbiol Infect 2021 Sep 18. Epub 2021 Sep 18.

Institute of Clinical Chemistry, University Hospital of Schleswig-Holstein, Kiel, Germany.

Objectives: To investigate the immune systems' response (and its influencing factors) to vaccination with BNT162b2 or mRNA-1273.

Methods: 531 vaccinees, recruited from health care professionals, donated samples before, in between, and after the administration of the two doses of the vaccine. T- and B-cell responses were examined via Interferon-γ-release assay as well as detection of antibodies against different epitopes of SARS-CoV-2 (S1 and NCP) via ELISA and binding surrogate neutralization assay. Results were correlated with influence factors such as age, sex, prior infection, vaccine received (BNT162b2 or mRNA-1273), and immunosuppression. Furthermore, antinuclear antibodies (ANA) were measured to screen for autoimmune responses following the vaccination with an mRNA vaccine.

Results: No markers of immunity against SARS-CoV-2 were found before the first vaccination. Two weeks after it, specific responses against SARS-CoV-2 were already measurable (median±median absolute deviation (MAD): anti-S1 IgG: 195.5±172.7 BAU/ml; IgA: 6.7±4.9 OD; surrogate neutralization: 39±23.7 %), which were significantly increased two weeks after the second dose (anti-S1 IgG: 3744±2571.4 BAU/ml; IgA: 12±0 OD; surrogate neutralization: 100±0 %, IFN-γ: 1897.2±886.7 mIU/ml). Responses were stronger for younger participants (this difference decreasing after the second dose). Further influences were previous infection with SARS-CoV-2 (causing significantly stronger responses after the first dose compared to unexposed individuals (p ≤ 0.0001)) and the vaccine received (significantly stronger reactions for recipients of mRNA-1273 after both doses (p < 0.05 - 0.0001)). Some forms of immunosuppression significantly impeded the immune response to the vaccination (with no observable immune response in three immunosuppressed participants). There was no significant induction of ANA by the vaccination (no change in qualitative ANA results (p = 0.2592), nor ANA titers (p = 0.08) from pre to post vaccination.

Conclusions: Both vaccines elicit strong and specific immune responses against SARS-CoV-2, which become detectable one week (T-cell-response) or two weeks (B-cell-response) after the first dose.
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http://dx.doi.org/10.1016/j.cmi.2021.09.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450229PMC
September 2021

A Case of Immunotherapy-responsive Non-paraneoplastic Encephalitis with Antibodies Against GAD, LGI1, and GABA Receptor.

Intern Med 2021 Jul 30. Epub 2021 Jul 30.

Division of Neurology, Kobe University Graduate School of Medicine, Japan.

A 62-year-old man showed abnormal behavior. Brain magnetic resonance imaging revealed multifocal lesions on T2-weighted images. Initial screening revealed that he was seropositive for antibodies against glutamate decarboxylase, which usually indicates treatment resistance to autoimmune encephalitis. Intensive immunosuppressive therapies, however, improved the neurological symptoms. In line with this, we also detected seropositivity for antibodies against leucine-rich glioma-inactivated 1 and gamma-aminobutyric acid A receptor (GABAR). Brain imaging and treatment responsiveness suggested that antibodies against GABAR were the main cause of symptoms. Furthermore, the patient showed the presence of triple anti-neural antibodies in the absence of malignancy and had a favorable clinical course.
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http://dx.doi.org/10.2169/internalmedicine.7846-21DOI Listing
July 2021

Analysis of SARS-CoV-2 reverse transcription-quantitative polymerase chain reaction cycle threshold values vis-à-vis anti-SARS-CoV-2 antibodies from a high incidence region.

Int J Infect Dis 2021 Jul 14;110:114-122. Epub 2021 Jul 14.

Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel, Lübeck, Germany.

Objectives: To examine the relationship between antibody status and cycle threshold (Ct) values, the prognostic value of the latter for COVID-19 patients, and the inter-assay comparability of SARS-CoV-2 Ct values.

Methods: In 347 COVID-19 inpatients, SARS-CoV-2 Ct values (via reverse transcription-quantitative polymerase chain reaction) on admission were compared between 2 assays and correlated with the antibody response (in the course of the disease), the clinical course and the time since onset of symptoms.

Results: Ct values for 2 of 3 target genes showed significant differences between the 2 assays used (P=0.012 and P<0.0001). Ct values were significantly higher for antibody positive patients (P<0.0001) and positively correlated with the amount of time since onset of symptoms (R: 0.332-0.363; P<0.001). Patients with fatal outcomes showed higher viral loads than survivors (P<0.0001).

Conclusions: Ct values depend strongly on assay used and target gene examined and should not be used as quantitative values to guide therapeutic or diagnostic decisions. The inverse association between antibody status and viral load suggests that antibodies contribute to the elimination of the virus, independent of the outcome, which is influenced by the viral load on admission and might depend more strongly on other parts of the immune response.
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http://dx.doi.org/10.1016/j.ijid.2021.07.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278831PMC
July 2021

Autoimmune Global Amnesia as Manifestation of AMPAR Encephalitis and Neuropathologic Findings.

Neurol Neuroimmunol Neuroinflamm 2021 07 20;8(4). Epub 2021 May 20.

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.

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.
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http://dx.doi.org/10.1212/NXI.0000000000001019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142837PMC
July 2021

Clinical correlates of anti-SARS-CoV-2 antibody profiles in Spanish COVID-19 patients from a high incidence region.

Sci Rep 2021 02 23;11(1):4363. Epub 2021 Feb 23.

Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lübeck, Germany.

Laboratory testing for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) consists of two pillars: the detection of viral RNA via rt-PCR as the diagnostic gold standard in acute cases, and the detection of antibodies against SARS-CoV-2. However, concerning the latter, questions remain about their diagnostic and prognostic value and it is not clear whether all patients develop detectable antibodies. We examined sera from 347 Spanish COVID-19 patients, collected during the peak of the epidemic outbreak in Spain, for the presence of IgA and IgG antibodies against SARS-CoV-2 and evaluated possible associations with age, sex and disease severity (as measured by duration of hospitalization, kind of respiratory support, treatment in ICU and death). The presence and to some degree the levels of anti-SARS-CoV-2 antibodies depended mainly on the amount of time between onset of symptoms and the collection of serum. A subgroup of patients did not develop antibodies at the time of sample collection. Compared to the patients that did, no differences were found. The presence and level of antibodies was not associated with age, sex, duration of hospitalization, treatment in the ICU or death. The case-fatality rate increased exponentially with older age. Neither the presence, nor the levels of anti-SARS-CoV-2 antibodies served as prognostic markers in our cohort. This is discussed as a possible consequence of the timing of the sample collection. Age is the most important risk factor for an adverse outcome in our cohort. Some patients appear not to develop antibodies within a reasonable time frame. It is unclear, however, why that is, as these patients differ in no respect examined by us from those who developed antibodies.
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http://dx.doi.org/10.1038/s41598-021-83969-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902674PMC
February 2021

Saliva for Detection of SARS-CoV-2.

N Engl J Med 2021 03 3;384(9):e31. Epub 2021 Feb 3.

University Hospital Schleswig-Holstein, Kiel, Germany

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http://dx.doi.org/10.1056/NEJMc2032165DOI Listing
March 2021

Bilateral vestibulopathy in anti-IgLON5 disease.

J Neurol 2021 Mar 23;268(3):1114-1116. Epub 2021 Jan 23.

Department of Neurology, University Hospital Schleswig Holstein, University of Lübeck, Campus Lübeck, Ratzeburger Allee 160, 23538, Lubeck, Germany.

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http://dx.doi.org/10.1007/s00415-020-10386-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914230PMC
March 2021

Antibody-related movement disorders - a comprehensive review of phenotype-autoantibody correlations and a guide to testing.

Neurol Res Pract 2020 20;2. Epub 2020 Feb 20.

Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK.

Background: Over the past decade increasing scientific progress in the field of autoantibody-mediated neurological diseases was achieved. Movement disorders are a frequent and often prominent feature in such diseases which are potentially treatable.

Main Body: Antibody-mediated movement disorders encompass a large clinical spectrum of diverse neurologic disorders occurring either in isolation or accompanying more complex autoimmune encephalopathic diseases. Since autoimmune movement disorders can easily be misdiagnosed as neurodegenerative or metabolic conditions, appropriate immunotherapy can be delayed or even missed. Recognition of typical clinical patterns is important to reach the correct diagnosis.

Conclusion: There is a growing number of newly discovered antibodies which can cause movement disorders. Several antibodies can cause distinctive phenotypes of movement disorders which are important to be aware of. Early diagnosis is important because immunotherapy can result in major improvement.In this review article we summarize the current knowledge of autoimmune movement disorders from a point of view focused on clinical syndromes. We discuss associated clinical phenomenology and antineuronal antibodies together with alternative etiologies with the aim of providing a diagnostic framework for clinicians considering underlying autoimmunity in patients with movement disorders.
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http://dx.doi.org/10.1186/s42466-020-0053-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7650144PMC
February 2020

Longitudinal Multi-omics Analyses Identify Responses of Megakaryocytes, Erythroid Cells, and Plasmablasts as Hallmarks of Severe COVID-19.

Immunity 2020 12 26;53(6):1296-1314.e9. Epub 2020 Nov 26.

Institute of Clinical Molecular Biology, Kiel University and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.

Temporal resolution of cellular features associated with a severe COVID-19 disease trajectory is needed for understanding skewed immune responses and defining predictors of outcome. Here, we performed a longitudinal multi-omics study using a two-center cohort of 14 patients. We analyzed the bulk transcriptome, bulk DNA methylome, and single-cell transcriptome (>358,000 cells, including BCR profiles) of peripheral blood samples harvested from up to 5 time points. Validation was performed in two independent cohorts of COVID-19 patients. Severe COVID-19 was characterized by an increase of proliferating, metabolically hyperactive plasmablasts. Coinciding with critical illness, we also identified an expansion of interferon-activated circulating megakaryocytes and increased erythropoiesis with features of hypoxic signaling. Megakaryocyte- and erythroid-cell-derived co-expression modules were predictive of fatal disease outcome. The study demonstrates broad cellular effects of SARS-CoV-2 infection beyond adaptive immune cells and provides an entry point toward developing biomarkers and targeted treatments of patients with COVID-19.
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http://dx.doi.org/10.1016/j.immuni.2020.11.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689306PMC
December 2020

Low-Avidity CD4 T Cell Responses to SARS-CoV-2 in Unexposed Individuals and Humans with Severe COVID-19.

Immunity 2020 12 26;53(6):1258-1271.e5. Epub 2020 Nov 26.

Institute of Immunology, Christian-Albrechts-University of Kiel & UKSH Schleswig-Holstein, Kiel, Germany.

CD4 T cells reactive against SARS-CoV-2 can be found in unexposed individuals, and these are suggested to arise in response to common cold coronavirus (CCCoV) infection. Here, we utilized SARS-CoV-2-reactive CD4 T cell enrichment to examine the antigen avidity and clonality of these cells, as well as the relative contribution of CCCoV cross-reactivity. SARS-CoV-2-reactive CD4 memory T cells were present in virtually all unexposed individuals examined, displaying low functional avidity and multiple, highly variable cross-reactivities that were not restricted to CCCoVs. SARS-CoV-2-reactive CD4 T cells from COVID-19 patients lacked cross-reactivity to CCCoVs, irrespective of strong memory T cell responses against CCCoV in all donors analyzed. In severe but not mild COVID-19, SARS-CoV-2-specific T cells displayed low functional avidity and clonality, despite increased frequencies. Our findings identify low-avidity CD4 T cell responses as a hallmark of severe COVID-19 and argue against a protective role for CCCoV-reactive T cells in SARS-CoV-2 infection.
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http://dx.doi.org/10.1016/j.immuni.2020.11.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689350PMC
December 2020

Clinical features, prognostic factors, and antibody effects in anti-mGluR1 encephalitis.

Neurology 2020 12 14;95(22):e3012-e3025. Epub 2020 Sep 14.

From the Institut d'Investigacions Biomèdiques August Pi i Sunyer (M. Spatola, M.P.P., E.M., M.R.R., F.G., J.D.), Barcelona, Spain; Ragon Institute of MGH, MIT and Harvard Medical School (M. Spatola), Cambridge, MA; Interdisciplinary Institute for Neuroscience (M.P.P.), University of Bordeaux, France; Neurology Division (M. Simabukuro), University of São Paulo, School of Medicine, Brazil; Centre de Référence des Syndromes Neurologiques Paranéoplasiques et des Encéphalites Autoimmunes (S.M.-C., A.L.P., J.H.), Hospices Civils de Lyon, Université de Lyon, Université Claude Bernard Lyon1, INMG, Inserm U1217/CNRS UMR 5310, France; Institute of Clinical Chemistry and Department of Neurology (K.-P.W.), Department of Neuropediatrics (J.S.), and Department of Neuroradiology (P.S.), University Hospital Schleswig Holstein, Lübeck, Germany; Faculdade Israelita de Ciências da Saúde Albert Einstein and General Neurology Division (L.A.D.), Federal University of São Paulo, Brazil; Institute of Neurology, Fondazione Policlinico Universitario "A. Gemelli" IRCCS (R.I.), Rome, Italy; Department of Neurology (C.K.), University Hospital Bonn; Epilepsy Center Bethel (C.G.B.), Krankenhaus Mara, Bielefeld, Germany; Division of Neuropathology and Neurochemistry (R.H.), Department of Neurology, Medical University of Vienna, Austria; Neuroimmunology (F.L.), Institute of Clinical Chemistry and Department of Neurology, University Hospital Schleswig Holstein, Kiel, Germany; Department of Neurology (M.J.T., P.S.S.), Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Neurology (M.R.R., J.D.), University of Pennsylvania, Philadelphia; University Hospital Clínic (F.G.), University of Barcelona; and Catalan Institution for Research and Advanced Studies (J.D.), Barcelona, Spain.

Objective: To clinically characterize patients with anti-metabotropic glutamate receptor (mGluR) 1 encephalitis, to identify prognostic factors, and to study the immunoglobulin G (IgG) subclasses and effects of antibodies on neuronal mGluR1 clusters.

Methods: Clinical information on new and previously reported patients was reviewed. Antibodies to mGluR1 and IgG subclasses were determined with brain immunohistochemistry and cell-based assays, and their effects on mGluR1 clusters were studied on rat hippocampal neurons.

Results: Eleven new patients were identified (10 adults, 1 child);4 were female. In these and 19 previously reported cases (n = 30, median age 55 years), the main clinical manifestation was a subacute cerebellar syndrome that in 25 (86%) patients was associated with behavioral/cognitive changes or other neurologic symptoms. A tumor was found in 3 of 26 (11%). Brain MRI was abnormal in 7 of 19 (37%) at onset and showed cerebellar atrophy in 10 of 12 (83%) at follow-up. Twenty-five of 30 (83%) patients received immunotherapy. Follow-up was available for 25: 13 (52%) had clinical stabilization; 10 (40%) showed significant improvement; and 2 died. At the peak of the disease, patients with bad outcome at 2 years (modified Rankin Scale score > 2, n = 7) were more likely to have higher degree of initial disability, as reflected by a worse Scale for Assessment and Rating of Ataxia score, and more frequent need of assistance to walk. Antibodies to mGluR1 were mainly IgG1 and caused a significant decrease of mGluR1 clusters in cultured neurons.

Conclusions: Anti-mGluR1 encephalitis manifests as a severe cerebellar syndrome, often resulting in long-term disability and cerebellar atrophy. The antibodies are pathogenic and cause significant decrease of mGluR1 clusters in cultured neurons.
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http://dx.doi.org/10.1212/WNL.0000000000010854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734921PMC
December 2020

Gender issues of antibody-mediated diseases in neurology: (NMOSD/autoimmune encephalitis/MG).

Ther Adv Neurol Disord 2020 25;13:1756286420949808. Epub 2020 Aug 25.

Department of Neurology, St. Josef Hospital Bochum, Ruhr University of Bochum, Gudrunstrasse 56, Bochum, 44791, Germany.

Neuromyelitis optica spectrum disorder (NMOSD), autoimmune encephalitis (AE), myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) are antibody-mediated neurological diseases. They have mostly female predominance, affecting many women during childbearing age. Interactions between the underlying disease (or necessary treatment) and pregnancy can occur in every of these illnesses. Herein, we present the characteristics of NMOSD, AE, MG and LEMS in general, and review published data regarding the influence of the different diseases on fertility, pregnancy, puerperium, treatment strategy during pregnancy and post-partum period, and menopause but also male factors. We summarise key elements that should be borne in mind when confronted with such cases.
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http://dx.doi.org/10.1177/1756286420949808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450460PMC
August 2020

Autoantibody-associated psychiatric syndromes: a systematic literature review resulting in 145 cases.

Psychol Med 2020 Sep 7:1-12. Epub 2020 Sep 7.

Section for Experimental Neuropsychiatry, Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Background: Autoimmune encephalitis (AE) is an important consideration during the diagnostic work-up of secondary mental disorders. Indeed, isolated psychiatric syndromes have been described in case reports of patients with underlying AE. Therefore, the authors performed a systematic literature review of published cases with AE that have predominant psychiatric/neurocognitive manifestations. The aim of this paper is to present the clinical characteristics of these patients.

Methods: The authors conducted a systematic Medline search via Ovid, looking for case reports/series of AEs with antineuronal autoantibodies (Abs) against cell surface/intracellular antigens combined with predominant psychiatric/neurocognitive syndromes. The same was done for patients with Hashimoto encephalopathy/SREAT. Only patients with signs of immunological brain involvement or tumors in their diagnostic investigations or improvement under immunomodulatory drugs were included.

Results: We identified 145 patients with AE mimicking predominant psychiatric/neurocognitive syndromes. Of these cases, 64% were female, and the mean age among all patients was 43.9 (±22.1) years. Most of the patients had Abs against neuronal cell surface antigens (55%), most frequently against the NMDA-receptor (N = 46). Amnestic/dementia-like (39%) and schizophreniform (34%) syndromes were the most frequently reported. Cerebrospinal fluid changes were found in 78%, electroencephalography abnormalities in 61%, and magnetic resonance imaging pathologies in 51% of the patients. Immunomodulatory treatment was performed in 87% of the cases, and 94% of the patients responded to treatment.

Conclusions: Our findings indicate that AEs can mimic predominant psychiatric and neurocognitive disorders, such as schizophreniform psychoses or neurodegenerative dementia, and that affected patients can be treated successfully with immunomodulatory drugs.
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http://dx.doi.org/10.1017/S0033291720002895DOI Listing
September 2020

Antiparanodal antibodies and IgG subclasses in acute autoimmune neuropathy.

Neurol Neuroimmunol Neuroinflamm 2020 09 24;7(5). Epub 2020 Jul 24.

From the Department of Neurology (L.A., A.-M.B., C.S., K.D.), University Hospital of Würzburg; Neuroimmunology Section (A.H., K.-P.W., R.J., F.L.), Institute of Clinical Chemistry, University Hospital of Schleswig-Holstein Campus Kiel; Department of Neurology (P.K.), University Hospital of Magdeburg; and Institute for Clinical Neurobiology (C.V.), University Hospital of Würzburg, Germany.

Objective: To determine whether IgG subclasses of antiparanodal autoantibodies are related to disease course and treatment response in acute- to subacute-onset neuropathies, we retrospectively screened 161 baseline serum/CSF samples and 66 follow-up serum/CSF samples.

Methods: We used ELISA and immunofluorescence assays to detect antiparanodal IgG and their subclasses and titers in serum/CSF of patients with Guillain-Barré syndrome (GBS), recurrent GBS (R-GBS), Miller-Fisher syndrome, and acute- to subacute-onset chronic inflammatory demyelinating polyradiculoneuropathy (A-CIDP). We evaluated clinical data retrospectively.

Results: We detected antiparanodal autoantibodies with a prevalence of 4.3% (7/161), more often in A-CIDP (4/23, 17.4%) compared with GBS (3/114, 2.6%). Longitudinal subclass analysis in the patients with GBS revealed IgG2/3 autoantibodies against Caspr-1 and against anti-contactin-1/Caspr-1, which disappeared at remission. At disease onset, patients with A-CIDP had IgG2/3 anti-Caspr-1 and anti-contactin-1/Caspr-1 or IgG4 anti-contactin-1 antibodies, IgG3 being associated with good response to IV immunoglobulins (IVIg). In the chronic phase of disease, IgG subclass of one patient with A-CIDP switched from IgG3 to IgG4.

Conclusion: Our data (1) confirm and extend previous observations that antiparanodal IgG2/3 but not IgG4 antibodies can occur in acute-onset neuropathies manifesting as monophasic GBS, (2) suggest association of IgG3 to a favorable response to IVIg, and (3) lend support to the hypothesis that in some patients, an IgG subclass switch from IgG3 to IgG4 may be the correlate of a secondary progressive or relapsing course following a GBS-like onset.
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http://dx.doi.org/10.1212/NXI.0000000000000817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413710PMC
September 2020

The Modern Epidemic of Syphilis.

N Engl J Med 2020 06;382(24):2379-2380

University Hospital Schleswig-Holstein Campus Lübeck, Lübeck, Germany

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http://dx.doi.org/10.1056/NEJMc2006129DOI Listing
June 2020

Antibodies to nodal/paranodal proteins in paediatric immune-mediated neuropathy.

Neurol Neuroimmunol Neuroinflamm 2020 07 2;7(4). Epub 2020 Jun 2.

From the Division of Neuropathology and Neurochemistry (D.D.S., G.R., M.W., I.K., R.H.), Department of Neurology, Medical University of Vienna, Austria; Department of Neurology (D.D.S.), University Hospital St. Poelten, Austria; Department of General Pediatrics, Neonatology and Pediatric Cardiology (M.K.), University Children's Hospital, Heinrich Heine University Duesseldorf, Germany; Department of Neuropediatric Rehabilitation (U.H.), Vamed Clinic Hattingen, Germany; Department of Neuropediatrics (U.S.), Charité University, Berlin, Germany; Paediatric Neurology (O.A.-M.), Great Ormond Street Hospital for Children, London, United Kingdom; Dubowitz Neuromuscular Centre (P.M.), Great Ormond Street Hospital for Children, London, United Kingdom; Nuffield Department of Clinical Neurosciences (S.R.), University of Oxford and Oxford University Hospitals NHS Foundation Trust; Department of Paediatric and Adolescent Medicine (C.S.), St Joseph Hospital, Berlin, Germany; Department of Pediatrics and Adolescent Medicine (M.F., M.B., R.S.), Medical University of Vienna, Austria; Department of Neurology (M.R., J.W.), Medical University of Innsbruck, Austria; Neuromuscular Diseases Unit (C.L., L.Q.), Hospital de la Santa Creu i Sant Pau, Universitat Autónoma de Barcelona, Spain; SMZ Süd (G.B.), Kaiser-Franz Josef Hospital with Gottfried von Preyer Children Hospital, Vienna, Austria; Institute of Clinical Chemistry (K.-P.W., R.J., F.L.), University Hospital Schleswig-Holstein, Kiel/Lübeck, Germany; Department of Neurology (F.L.), University Hospital Schleswig-Holstein, Kiel, Germany; and Department of Pediatric Neurology (K.R.), Witten/Herdecke University, Children's Hospital Datteln, Germany.

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http://dx.doi.org/10.1212/NXI.0000000000000763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286658PMC
July 2020

CASPR2 autoimmunity in children expanding to mild encephalopathy with hypertension.

Neurology 2020 06 18;94(22):e2290-e2301. Epub 2020 May 18.

From the Division of Pediatric Epileptology (S. Syrbe), Centre for Paediatrics and Adolescent Medicine, University Hospital Heidelberg, Germany; Division of Pediatric Neurology (G.M.S., R.S.), University Children's Hospital Zurich; Department of Neurology (J.B., R.I.F.), University & University Hospitals of Geneva, Switzerland; Division of Pediatric Neurology (I.B.), Developmental Neurology and Social Pediatrics, Department of Pediatrics and Epilepsy Center for Children, Adolescents and Adults, University Hospital LMU Munich; Laboratory Krone (C.I.B., C.G.B.), Bad Salzuflen; Department of Pediatrics and Pediatric Neurology (P.H.), Faculty of Medicine, Georg August University, Goettingen; Department of Child Neurology (J.K., A.W.), University Children's Hospital, Tuebingen; Epilepsy Center Bethel (T.P., C.G.B.), Krankenhaus Mara, Bielefeld, Germany; Clinic of Immunology (E.P.-M.), University Hospital Zurich; Kantonsspital Graubünden (S. Schmid, S. Strozzi), Chur; Pediatric Nephrology Unit (M.W.), University Children's Hospital Zurich, Switzerland; Division of Child Neurology and Metabolic Medicine (A.Z.), Centre for Paediatrics and Adolescent Medicine, University Hospital Heidelberg; Institute of Clinical Chemistry (K.-P.W., F.L.), Neuroimmunology Section, University Hospital Schleswig-Holstein Kiel/Lübeck; Department of Neurology (K.-P.W.), University of Lübeck; and Department of Neurology (F.L.), Christian-Albrechts-University Kiel, Germany.

Objective: To delineate autoimmune disease in association with contactin-associated protein 2 (CASPR2) antibodies in childhood, we reviewed the clinical phenotype of children with CASPR2 antibodies.

Methods: Retrospective assessment of patients recruited through laboratories specialized in autoimmune CNS disease.

Results: Ten children with serum CASPR2 antibodies were identified (age at manifestation 18 months to 17 years). Eight children with CASPR2 antibody titers from ≥1:160 to 1:5,120 had complex autoimmune diseases with an age-dependent clinical phenotype. Two children with structural epilepsy due to CNS malformations harbored nonspecific low-titer CASPR2 antibodies (serum titers 1:80). The clinical symptoms of the 8 children with high-titer CASPR2 antibodies were general weakness (8/8), sleep dysregulation (8/8), dysautonomia (8/8) encephalopathy (7/8), neuropathic pain (7/8), neuromyotonia (3/8), and flaccid paresis (3/8). Adolescents (3/8) showed pain, neuromyotonia, and encephalopathy, whereas younger children (5/8) displayed severe hypertension, encephalopathy, and hormonal dysfunction mimicking a systemic disease. No tumors were identified. Motor symptoms remitted with immunotherapy. Mild behavioral changes persisted in 1 child, and autism spectrum disorder was diagnosed during follow-up in a young boy.

Conclusion: High-titer CASPR2 antibodies are associated with Morvan syndrome in children as young as 2 years. However, CASPR2 autoimmunity mimics systemic disease and hypertensive encephalopathy in children younger than 7 years. The outcome following immunotherapy was mostly favorable; long-term behavioral impairment may occur in younger children.
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http://dx.doi.org/10.1212/WNL.0000000000009523DOI Listing
June 2020

Terminology and definition of 'antinuclear antibodies': history and current debate.

Ann Rheum Dis 2020 Mar 30. Epub 2020 Mar 30.

Institute of Clinical Chemistry, University Hospital Schleswig Holstein, Lübeck, Germany.

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http://dx.doi.org/10.1136/annrheumdis-2020-217166DOI Listing
March 2020

Transient MOG antibody seroconversion associated with immunomodulating therapy.

Mult Scler Relat Disord 2020 Jan 28;37:101420. Epub 2019 Sep 28.

Department of Neurology, Otto-von-Guericke University, Leipziger Straße 44, 39120 Magdeburg, Germany; Charité-Universitätsmedizin Berlin, Department of Neurology, Germany; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.

Immunoglobulin G (IgG) autoantibodies targeting myelin oligodendrocyte glycoprotein (MOG) have recently been associated with autoimmune CNS demyelination. We present the case of a 35-year-old patient who was seronegative for MOG-IgG (as confirmed by means of three independent immunoassays) during two corticosteroid-responsive attacks of brainstem encephalitis and optic neuritis, respectively, but turned positive for MOG-IgG under treatment with interferon-beta (IFN-beta), which was commenced 6 months after onset of the first attack. MOG-IgG serum levels declined after therapy was switched to glatiramer acetate. The fact that seroconversion was first observed under treatment with IFN-beta is in accordance with previous evidence suggesting a role of IFN-beta in disease exacerbation in antibody-mediated disorders.
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http://dx.doi.org/10.1016/j.msard.2019.101420DOI Listing
January 2020

Autoimmune encephalitis as a differential diagnosis of schizophreniform psychosis: clinical symptomatology, pathophysiology, diagnostic approach, and therapeutic considerations.

Eur Arch Psychiatry Clin Neurosci 2020 Oct 12;270(7):803-818. Epub 2020 Mar 12.

Section for Experimental Neuropsychiatry, Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Primary schizophreniform psychoses are thought to be caused by complex gene-environment interactions. Secondary forms are based on a clearly identifiable organic cause, in terms of either an etiological or a relevant pathogenetic factor. The secondary or "symptomatic" forms of psychosis have reentered the focus stimulated by the discovery of autoantibody (Ab)-associated autoimmune encephalitides (AEs), such as anti-NMDA-R encephalitis, which can at least initially mimic variants of primary psychosis. These newly described secondary, immune-mediated schizophreniform psychoses typically present with the acute onset of polymorphic psychotic symptoms. Over the course of the disease, other neurological phenomena, such as epileptic seizures, movement disorders, or reduced levels of consciousness, usually arise. Typical clinical signs for AEs are the acute onset of paranoid hallucinatory symptoms, atypical polymorphic presentation, psychotic episodes in the context of previous AE, and additional neurological and medical symptoms such as catatonia, seizure, dyskinesia, and autonomic instability. Predominant psychotic courses of AEs have also been described casuistically. The term autoimmune psychosis (AP) was recently suggested for these patients. Paraclinical alterations that can be observed in patients with AE/AP are inflammatory cerebrospinal fluid (CSF) pathologies, focal or generalized electroencephalographic slowing or epileptic activity, and/or suspicious "encephalitic" imaging findings. The antibody analyses in these patients include the testing of the most frequently found Abs against cell surface antigens (NMDA-R, CASPR2, LGI1, AMPA-R, GABA-R), intracellular antigens (Hu, Ri, Yo, CV2/CRMP5, Ma2 [Ta], amphiphysin, GAD65), thyroid antigens (TG, TPO), and antinuclear Abs (ANA). Less frequent antineuronal Abs (e.g., against DPPX, GABA-R, glycine-R, IgLON5) can be investigated in the second step when first step screening is negative and/or some specific clinical factors prevail. Beyond, tissue-based assays on brain slices of rodents may detect previously unknown antineuronal Abs in some cases. The detection of clinical and/or paraclinical pathologies (e.g., pleocytosis in CSF) in combination with antineuronal Abs and the exclusion of alternative causes may lead to the diagnosis of AE/AP and enable more causal therapeutic immunomodulatory opportunities.
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http://dx.doi.org/10.1007/s00406-020-01113-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7474714PMC
October 2020

PTH Immunoassay Interference Due to Human Anti-Mouse Antibodies in a Subject With Obesity With Normal Parathyroid Function.

J Clin Endocrinol Metab 2019 12;104(12):5840-5842

Institute of Clinical Chemistry, University Hospital of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.

Context: Immunoassay interference has been most often found with prolactin measurement. However, only few data exist on immunoassay interference for other hormones.

Case Description: A 36-year-old woman with obesity (body mass index, 31 kg/m2) had regularly attended our endocrine unit for type 2 diabetes therapy. When she was included as a control subject in a study for obesity management, detailed laboratory testing was performed, including PTH. In the absence of clinical symptoms, she presented with normal calcium, phosphate, and vitamin D levels. However, the PTH levels were >5000 ng/L. These results were obtained using the Roche Elecsys electrochemiluminescence assay. Repeated measurements with this assay (mouse antibody) led to the same findings. However, using an Euroimmun assay (goat antibody), the exact PTH values were measured at 18.0 ng/L. After pretreatment with a heterophilic antibody blocking reagent, the results of the Roche assay had decreased to a normal level. This phenomenon was explained by the detection of human anti-mouse antibodies in the proband's serum.

Conclusions: In cases of prolactin immunoassay interference, endogenous antibodies will bind to the hormone in vivo, resulting in complexes of a high molecular weight that are less efficiently cleared by the kidneys and, thus, accumulate in the blood. In contrast, the PTH values >5000 ng/L detected in our subject most likely had resulted from the specific interference of the human anti-mouse antibodies present in the proband's serum with the assay antibody, resulting in artificial stimulation of the Roche assay detection system ex vivo.
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http://dx.doi.org/10.1210/jc.2019-01321DOI Listing
December 2019

Antibodies against neural antigens in patients with acute stroke: joint results of three independent cohort studies.

J Neurol 2019 Nov 29;266(11):2772-2779. Epub 2019 Jul 29.

Department of Neuroscience, Comprehensive Stroke Center, Hospital Clinic, Barcelona, Spain.

Background And Purpose: Ischemic stroke (IS) and hemorrhagic stroke (HemS) typically lead to a breakdown of the blood-brain barrier with neural antigen presentation. This presentation could potentially generate destructive auto-immune responses. Pre-existing antineuronal and antiglial antibodies (AA), predominantly NMDA receptor antibodies, have been reported in patients with stroke. This article summarizes three independent prospective studies, the Lübeck cohort (LC), Barcelona cohort (BC), and Heidelberg cohort (HC), exploring the frequency and clinical relevance of AA in patients with acute stroke (AS).

Methods: In all cohorts together, 344 consecutive patients admitted with AS (322 × IS, 22 × HemS) were screened for AA in serum at admission. Clinical outcome parameters as well as a second AA screening were available at 30 days in the LC or at 90 days in the BC. A control group was included in the BC (20 subjects free from neurological disease) and the HC (78 neurological and ophthalmological patients without evidence for stroke).

Results: The rate of positivity for AA was similar in control subjects and AS patients (13%, 95% CI [7%, 22%] vs. 13%, 95% CI [10%, 17%]; p = 0.46) with no significant difference between cohorts (LC 25/171, BC 12/75, HC 9/98). No patient had developed new AA after 30 days, whereas 2 out of 60 patients had developed new AA after 90 days. AA positive patients did not exhibit significant differences to AA negative patients in stroke subtype (LC, BC), initial stroke severity (BC, LC, HC), infarct volume (BC), and functional status at admission (BC, LC, HC) and follow-up (BC, LC).

Conclusions: AS does not induce AA to a relevant degree. Pre-existing AA can be found in the serum of stroke patients, but they do not have a significant association with clinical features and outcomes.
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http://dx.doi.org/10.1007/s00415-019-09470-2DOI Listing
November 2019

No association between Parkinson disease and autoantibodies against NMDA-type glutamate receptors.

Transl Neurodegener 2019 3;8:11. Epub 2019 Apr 3.

1Department of Neurology, University Hospital Schleswig Holstein, Arnold-Heller Str. 3, 24105 Kiel, Germany.

Background: IgG-class autoantibodies to N-Methyl-D-Aspartate (NMDA)-type glutamate receptors define a novel entity of autoimmune encephalitis. Studies examining the prevalence of NMDA IgA/IgM antibodies in patients with Parkinson disease with/without dementia produced conflicting results. We measured NMDA antibodies in a large, well phenotyped sample of Parkinson patients without and with cognitive impairment ( = 296) and controls ( = 295) free of neuropsychiatric disease. Detailed phenotyping and large numbers allowed statistically meaningful correlation of antibody status with diagnostic subgroups as well as quantitative indicators of disease severity and cognitive impairment.

Methods: NMDA antibodies were analysed in the serum of patients and controls using well established validated assays. We used anti-NMDA antibody positivity as the main independent variable and correlated it with disease status and phenotypic characteristics.

Results: The frequency of NMDA IgA/IgM antibodies was lower in Parkinson patients (13%) than in controls (22%) and higher than in previous studies in both groups. NMDA IgA/IgM antibodies were neither significantly associated with diagnostic subclasses of Parkinson disease according to cognitive impairment, nor with quantitative indicators of disease severity and cognitive impairment. A positive NMDA antibody status was positively correlated with age in controls but not in Parkinson patients.

Conclusion: It is unlikely albeit not impossible that NMDA antibodies play a significant role in the pathogenesis or progression of Parkinson disease e.g. to Parkinson disease with dementia, while NMDA IgG antibodies define a separate disease of its own.
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http://dx.doi.org/10.1186/s40035-019-0153-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446289PMC
April 2019

In vitro neuronal network activity as a new functional diagnostic system to detect effects of Cerebrospinal fluid from autoimmune encephalitis patients.

Sci Rep 2019 04 3;9(1):5591. Epub 2019 Apr 3.

Department of Neurology and Epileptology, Hertie Institute of Clinical Brain Research, University of Tübingen, Tübingen, Germany.

The intent of this study was to investigate if cerebrospinal fluid (CSF) from autoimmune encephalitis (AE) patients regulates in vitro neuronal network activity differentially to healthy human control CSF (hCSF). To this end, electrophysiological effects of CSF from AE patients or hCSF were measured by in vitro neuronal network activity (ivNNA) recorded with microelectrode arrays (MEA). CSF from patients with either N-methyl-D-aspartate-receptor-antibody (pCSF, n = 7) or Leucine-rich-glioma-inactivated-1-Ab (pCSF, n = 6) associated AE suppressed global spiking activity of neuronal networks by a factor of 2.17 (p < 0.05) or 2.42 (p < 0.05) compared to hCSF. The former also suppressed synchronous network bursting by a factor of 1.93 (p < 0.05) in comparison to hCSF (n = 13). As a functional diagnostic test, this parameter reached a sensitivity of 86% for NMDAR-Ab- and 100% for LGI1-Ab-associated AE vs. hCSF at a specificity of 85%. To explore if modulation at the NMDAR influences effects of hCSF or pathological CSF, we applied the NMDAR-antagonist 2-Amino-5-phosphono-pentanoic acid (AP5). In CSF from NMDAR-Ab-associated AE patients, spike rate reduction by AP5 was more than 2-fold larger than in hCSF (p < 0.05), and network burst rate reduction more than 18-fold (p < 0.01). Recording ivNNA might help discriminating between functional effects of CSF from AE patients and hCSF, and thus could be used as a functional diagnostic test in AE. The pronounced suppression of ivNNA by CSF from NMDAR-Ab-associated AE patients and simultaneous antagonism at the NMDAR by AP5, particularly in burst activity, compared to hCSF plus AP5, confirms that the former contains additional ivNNA-suppressing factors.
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http://dx.doi.org/10.1038/s41598-019-41849-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447720PMC
April 2019

Anti-Amphiphysin-associated limbic encephalitis in a 72-year-old patient with aortic angiosarcoma.

BMJ Case Rep 2019 Mar 14;12(3). Epub 2019 Mar 14.

Department of Neurology, University Hospital Schleswig-Holstein, Lübeck, Germany.

Paraneoplastic autoimmune encephalopathic syndromes have been described most often in association with small cell lung cancer or breast cancer, tumours of the ovaries, testes, lymphoma and thymoma. Antibodies associated with paraneoplastic encephalopathies are, among others, anti-Hu, anti-Ma2 and, in part, anti-N-methyl-D-aspartate(NMDA)-receptor antibodies. Here, we present the case of a 72-year-old patient hospitalised due to progressive cognitive decline and disorientation. Diagnostic workup revealed paraneoplastic anti-amphiphysin associated limbic encephalitis on the basis of an aortic angiosarcoma with metastases to kidney, muscle and bones. Highly aggressive chemotherapy as well as immunosuppressive therapy and cytoreductive laparoscopic nephrectomy were initiated. However, follow-up revealed further tumour progress and a worsening of neurological symptoms.
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http://dx.doi.org/10.1136/bcr-2018-226798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6424176PMC
March 2019

Sez6l2-antibody-associated progressive cerebellar ataxia: a differential diagnosis of atypical parkinsonism.

J Neurol 2019 Feb 20;266(2):522-524. Epub 2018 Nov 20.

Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.

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http://dx.doi.org/10.1007/s00415-018-9115-1DOI Listing
February 2019

Autoantibody-Mediated Encephalitis.

Dtsch Arztebl Int 2018 11;115(40):666-673

Institute of Clinical Chemistry, University Hospital Schleswig-Holstein.

Background: Acute and subacute disturbances of wakefulness and cognitive function are common neurological manifestations in the hospital and in outpatient care. An important element of the differential diagnosis was described only a few years ago: autoimmune encephalitis, a condition whose diagnosis and treatment pose an interdisciplinary challenge.

Methods: This review is based on pertinent publications from the years 2005-2017 that were retrieved by a selective search in PubMed, and on the authors' personal experience and case reports.

Results: The incidence of autoimmune encephalitis in Germany is estimated at 8-15 cases per million persons per year. In some patients with psychotic manifestations or impaired consciousness of acute or subacute onset, an autoimmune patho - genesis can be demonstrated by the laboratory detection of autoantibodies against neuronal target antigens (e.g., glutamate receptors). Testing of this type should be performed in patients with inflammatory changes in the cerebrospinal fluid or on magnetic resonance imaging (MRI), or those who have had an otherwise unexplained first epileptic seizure or status epilepticus. The cumulative sensitivity of testing for all potentially causative antineuronal antibodies in patients with clinically defined autoimmune encephalitis is estimated at 60-80 %. Figures on cumulative specificity are currently unavailable.

Conclusion: The detection of antineuronal antibodies in patients with the corresponding appropriate symptoms implies the diagnosis of autoimmune encephalitis. Observational studies have shown that rapidly initiated immunosuppressive treatment improves these patients' outcomes. Further studies are needed to determine the positive predictive value of antineuronal antibody detection and to develop further treatment options under randomized and controlled conditions.
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http://dx.doi.org/10.3238/arztebl.2018.0666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234470PMC
November 2018

Beyond the limbic system: disruption and functional compensation of large-scale brain networks in patients with anti-LGI1 encephalitis.

J Neurol Neurosurg Psychiatry 2018 11 9;89(11):1191-1199. Epub 2018 Jun 9.

Department of Neurology, Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

Objective: Hippocampal inflammation in anti-LGI1 encephalitis causes memory deficits, seizures and behavioural abnormalities. Recent findings suggest that extralimbic brain areas are additionally affected and that patients also suffer from non-limbic cognitive symptoms. Moreover, up to 60% of patients show no structural MRI abnormalities in the acute disease stage. We therefore investigated whether functional connectivity analyses can identify brain network changes underlying disease-related symptoms.

Methods: We studied 27 patients and a matched healthy control group using structural and functional MRI. Intrinsic functional networks were analysed using Independent Component Analysis and Dual Regression. Cognitive testing covered working memory, episodic memory, attention and executive function.

Results: Our analysis revealed functional connectivity alterations in several large-scale networks, including the default mode network (DMN) which showed an aberrant structure-function relationship with the damaged hippocampus. In addition, connectivity in the sensorimotor, salience and higher visual networks was impaired independent of hippocampal damage. Increased connectivity in ventral and dorsal DMN regions significantly correlated with better memory performance. In contrast, stronger connectivity of the insula with the salience network and DMN was linked to impaired memory function.

Conclusions: Anti-LGI1 encephalitis is associated with a characteristic pattern of widespread functional network alterations. Increased DMN connectivity seems to represent a compensatory mechanism for memory impairment induced by hippocampal damage. Network analyses may provide a key to the understanding of clinical symptoms in autoimmune encephalitis and reveal changes of brain function beyond apparent structural damage.
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http://dx.doi.org/10.1136/jnnp-2017-317780DOI Listing
November 2018

Excessively increased CSF glutamate levels in GABA-receptor antibody associated encephalitis: A case report.

J Neurol Sci 2018 05 27;388:10-11. Epub 2018 Feb 27.

Department of Neurology, University of Luebeck, Luebeck, Germany; Institute of Clinical Chemistry, University Hospital of Schleswig-Holstein, Luebeck, Germany. Electronic address:

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http://dx.doi.org/10.1016/j.jns.2018.02.041DOI Listing
May 2018

Genetic predisposition in anti-LGI1 and anti-NMDA receptor encephalitis.

Ann Neurol 2018 04;83(4):863-869

Department of Neurology, Christian-Albrechts-University Kiel, Germany.

We performed a genome-wide association study in 1,194 controls and 150 patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR, n = 96) or anti-leucine-rich glioma-inactivated1 (anti-LGI1, n = 54) autoimmune encephalitis. Anti-LGI1 encephalitis was highly associated with 27 single-nucleotide polymorphisms (SNPs) in the HLA-II region (leading SNP rs2858870 p = 1.22 × 10 , OR = 13.66 [7.50-24.87]). Potential associations, below genome-wide significance, were found with rs72961463 close to the doublecortin-like kinase 2 gene (DCLK2) and rs62110161 in a cluster of zinc-finger genes. HLA allele imputation identified association of anti-LGI1 encephalitis with HLA-II haplotypes encompassing DRB1*07:01, DQA1*02:01 and DQB1*02:02 (p < 2.2 × 10 ) and anti-NMDAR encephalitis with HLA-I allele B*07:02 (p = 0.039). No shared genetic risk factors between encephalitides were identified. Ann Neurol 2018;83:863-869.
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http://dx.doi.org/10.1002/ana.25216DOI Listing
April 2018
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