Publications by authors named "Thomas Berger"

547 Publications

[All in the mix? Blended psychotherapy as an example of digitalization in psychotherapy].

Psychotherapeut (Berl) 2021 Jul 9:1-8. Epub 2021 Jul 9.

Abteilung Klinische Psychologie und Psychotherapie, Institut für Psychologie, Universität Bern, Fabrikstr. 8, 3012 Bern, Schweiz.

Background: Over the last decades various approaches to digitalization of psychotherapy (PT) have been developed. The concept of blended PT, the combination of face to face and online interventions is one such example. While research interest on blended PT has greatly increased in the past years, the implementation of blended PT has lagged behind in German speaking countries. Also, due to the global pandemic caused by the coronavirus disease 2019 (COVID-19), blended PT and other online approaches seem to be more relevant than ever before.

Objective: The aim is to give an overview on the various forms of blended PT. Furthermore, the efficacy, the perspectives of patients and therapists as well as the topic of implementation are discussed.

Material And Methods: Narrative review of the literature on the topic of blended PT. Important considerations and findings are classified and described based on a comprehensive search.

Results: Blended psychotherapy is a concept in need of definition. By taking inspiration from blended learning concepts, we propose that a definition of blended psychotherapy should consider different levels of blends and may also consider the transforming effect on face to face psychotherapy. In transforming blends face to face PT is fundamentally changed. For some forms of blended PT the effectiveness has already been confirmed but for others there is an urgent need for research. Compared to face to face PT and purely online therapy, blended psychotherapy could provide several advantages.

Conclusion: The interest in blended PT is increasing among patients and therapists. To be able to successfully provide evidence-based blended PT, close cooperation between science, institutions, therapists and relevant stakeholders is needed.
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http://dx.doi.org/10.1007/s00278-021-00524-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268619PMC
July 2021

Stakeholders' views on online interventions to prevent common mental health disorders in adults implemented into existing healthcare systems in Europe.

Eur J Public Health 2021 Jul;31(Supplement_1):i55-i63

Ferdinand Porsche FernFH-Distance Learning University of Applied Sciences, Wiener Neustadt 2700, Austria.

Background: Online preventive interventions can help to reduce the incidence of mental disorders. Whereas knowledge on stakeholders' attitudes and factors relevant for successfully integrating online treatment into existing healthcare systems is available, knowledge is scarce for online prevention.

Methods: Stakeholders from Germany, Switzerland, Austria and Spain were surveyed. Potential facilitators/delivery staff (e.g. psychologists, psychotherapists) completed an online questionnaire (n = 183), policy makers (i.e. from the governing sector or health insurance providers) participated in semi-structured interviews (n = 16) and target groups/potential users of mental illness prevention (n = 49) participated in ten focus groups. Thematic analysis was used to identify their experiences with and attitudes and needs regarding online programmes to prevent mental disorders. Additionally, it was examined which groups they consider underserved and which factors they consider as fostering and hindering for reach, adoption, implementation and maintenance (cf. RE-AIM model) when integrating online prevention into existing healthcare systems.

Results: Main advantages of online mental illness prevention are perceived in low structural and psychological barriers. Lack of personal contact, security, privacy and trust concerns were discussed as disadvantages. Relevant needs are high usability and target group appropriateness, evidence for effectiveness and the use of motivational tools.

Conclusions: Positive attitudes among stakeholders are the key for successful integration of online mental illness prevention into existing healthcare systems. Potential facilitators/delivery staff must receive training and support to implement these programmes; the programmes must be attractive and continuously evaluated, updated and promoted to ensure ongoing reach; and existing infrastructure and contextual factors must be considered.
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http://dx.doi.org/10.1093/eurpub/ckab043DOI Listing
July 2021

Online prevention programmes for university students: stakeholder perspectives from six European countries.

Eur J Public Health 2021 Jul;31(Supplement_1):i64-i70

King's College London, Institute of Psychiatry, Psychology and Neuroscience, London, UK.

Background: Students beginning university are at a heightened risk for developing mental health disorders. Online prevention and early intervention programmes targeting mental health have the potential to reduce this risk, however, previous research has shown uptake to be rather poor. Understanding university stakeholders' (e.g. governing level and delivery staff [DS] and students) views and attitudes towards such online prevention programmes could help with their development, implementation and dissemination within university settings.

Methods: Semi-structured interviews, focus groups and online surveys were completed with staff at a governing level, university students and DS (i.e. student health or teaching staff) from six European countries. They were asked about their experiences with, and needs and attitudes towards, online prevention programmes, as well as the factors that influence the translation of these programmes into real-world settings. Results were analyzed using thematic analysis.

Results: Participating stakeholders knew little about online prevention programmes for university settings; however, they viewed them as acceptable. The main themes to emerge were the basic conditions and content of the programmes, the awareness and engagement, the resources needed, the usability and the responsibility and ongoing efforts to increase reach.

Conclusions: Overall, although these stakeholders had little knowledge about online prevention programmes, they were open to the idea of introducing them. They could see the potential benefits that these programmes might bring to a university setting as a whole and the individual students and staff members.
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http://dx.doi.org/10.1093/eurpub/ckab040DOI Listing
July 2021

Reactivity of Hydrogen-Related Electron Centers in Powders, Layers, and Electrodes Consisting of Anatase TiO Nanocrystal Aggregates.

J Phys Chem C Nanomater Interfaces 2021 Jul 22;125(25):13809-13818. Epub 2021 Jun 22.

Department of Chemistry and Physics of Materials, University of Salzburg, Jakob-Haringer-Strasse 2a, A-5020 Salzburg, Austria.

Anatase TiO nanoparticle aggregates were used as model systems for studying at different water activities the reactivity of electron centers at semiconductor surfaces. The investigated surface conditions evolve from a solid/vacuum interface to a solid/bulk electrolyte interface. Hydrogen-related electron centers were generated either chemically-upon sample exposure to atomic hydrogen at the semiconductor/gas interface-or electrochemically-upon bias-induced charge accumulation at the semiconductor/electrolyte interface. Based on their corresponding spectroscopic and electrochemical fingerprints, we investigated the reactivity of hydrogen-related electron centers as a function of the interfacial condition and at different levels of complexity, that is, (i) for dehydrated and (partially) dehydroxylated oxide surfaces, (ii) for oxide surfaces covered by a thin film of interfacial water, and (iii) for oxide surfaces in contact with a 0.1 M HClO aqueous solution. Visible (Vis) and infrared (IR) spectroscopy evidence a chemical equilibrium between hydrogen atoms in the gas phase and-following their dissociation-electron/proton centers in the oxide. The excess electrons are either localized forming (Vis-active) Ti centers or delocalized as (IR-active) free conduction band electrons. The addition of molecular oxygen to chemically reduced anatase TiO nanoparticle aggregates leads to a quantitative quenching of Ti centers, while a fraction of ∼10% of hydrogen-derived conduction band electrons remains in the oxide pointing to a persistent hydrogen doping of the semiconductor. Neither trapped electrons (i.e., Ti centers) nor conduction band electrons react with water or its adsorption products at the oxide surface. However, the presence of an interfacial water layer does not impede the electron transfer to molecular oxygen. At the semiconductor/electrolyte interface, inactivity of trapped electrons with regard to water reduction and electron transfer to oxygen were evidenced by cyclic voltammetry.
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http://dx.doi.org/10.1021/acs.jpcc.1c01580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256420PMC
July 2021

[The corona pandemic and multiple sclerosis: vaccinations and their implications for patients-Part 1: recommendations].

Nervenarzt 2021 Jul 7. Epub 2021 Jul 7.

Klinik und Poliklinik für Neurologie, Neuroimmunologische Sektion, Universitätsmedizin Rostock, Rostock, Deutschland.

The ongoing COVID-19 pandemic is a global health crisis. New challenges are constantly emerging especially for the healthcare system, not least with the emergence of various viral mutations. Given the variety of immunomodulatory and immunosuppressive therapies for multiple sclerosis (MS) and the immense developments in vaccine production, there is a high need of information for people with MS. The aim of this article is therefore to provide an overview of MS and COVID-19 as well as to clarify the implications for patients with MS, especially regarding vaccination and to formulate appropriate recommendations.
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http://dx.doi.org/10.1007/s00115-021-01155-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261803PMC
July 2021

[The corona pandemic and multiple sclerosis: vaccinations and their implications for patients-Part 2: vaccine technologies].

Nervenarzt 2021 Jul 7. Epub 2021 Jul 7.

Klinik und Poliklinik für Neurologie, Neuroimmunologische Sektion, Universitätsmedizin Rostock, Rostock, Deutschland.

Along with the challenges posed by the globally circulating COVID-19 pandemic, there have been some epochal advances in the field of vaccine technologies. In addition to the traditionally used dead, live and protein-based vaccines, vector-based and gene-based vaccines gained enormous attention in the course of this health crisis. The aim of this article is to provide an overview of multiple sclerosis (MS) and vaccination, recent advances in the SARS-CoV‑2 vaccine landscape as well as a detailed discussion of the various vaccine technologies. Finally, clear recommendations in the context of disease-modifying treatment and vaccination in MS are highlighted.
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http://dx.doi.org/10.1007/s00115-021-01154-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261806PMC
July 2021

Cerebrospinal Fluid Findings in 541 Patients With Clinically Isolated Syndrome and Multiple Sclerosis: A Monocentric Study.

Front Immunol 2021 17;12:675307. Epub 2021 Jun 17.

Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.

Background: Reports on typical routine cerebrospinal fluid (CSF) findings are outdated owing to novel reference limits (RL) and revised diagnostic criteria of Multiple Sclerosis (MS).

Objective: To assess routine CSF parameters in MS patients and the frequency of pathologic findings by applying novel RL.

Methods: CSF white blood cells (WBC), CSF total protein (CSF-TP), CSF/serum albumin quotient (Q), intrathecal synthesis of immunoglobulins (Ig) A, M and G, oligoclonal IgG bands (OCB) were determined in patients with clinically isolated syndrome (CIS) and MS.

Results: Of 541 patients 54% showed CSF pleocytosis with a WBC count up to 40/μl. CSF cytology revealed lymphocytes, monocytes and neutrophils in 99%, 41% and 9% of patients. CSF-TP and Q were increased in 19% and 7% applying age-corrected RL as opposed to 34% and 26% with conventional RL. Quantitative intrathecal IgG, IgA and IgM synthesis were present in 65%, 14% and 21%; OCB in 95% of patients. WBC were higher in relapsing than progressive MS and predicted, together with monocytes, the conversion from CIS to clinically definite MS. Intrathecal IgG fraction was highest in secondary progressive MS.

Conclusions: CSF profile in MS varies across disease courses. Blood-CSF-barrier dysfunction and intrathecal IgA/IgM synthesis are less frequent when the novel RL are applied.
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http://dx.doi.org/10.3389/fimmu.2021.675307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248497PMC
June 2021

Bruton's tyrosine kinase inhibition in the treatment of preclinical models and multiple sclerosis.

Curr Pharm Des 2021 Jul 1. Epub 2021 Jul 1.

Department of Neurology, Landesklinikum Mistelbach-Gänserndorf, Mistelbach. Austria.

Significant progress has been made in understanding the immunopathogenesis of multiple sclerosis (MS) over recent years. Successful clinical trials with CD20-depleting monoclonal antibodies have corroborated the fundamental role of B cells in the pathogenesis of MS and reinforced the notion that cells of the B cell lineage are an attractive treatment target. Therapeutic inhibition of Bruton's tyrosine kinase (BTK), an enzyme involved in B cell and myeloid cell activation and function, is regarded as a next-generation approach that aims to attenuate both errant innate and adaptive immune functions. Moreover, brain-penetrant BTK inhibitors may impact compartmentalized inflammation and neurodegeneration within the central nervous system by targeting brain-resident B cells and microglia, respectively. Preclinical studies in animal models of MS corroborated an impact of BTK inhibition on meningeal inflammation and cortical demyelination. Notably, BTK inhibition attenuated the antigen-presenting capacity of B cells and the generation of encephalitogenic T cells. Evobrutinib, a selective oral BTK inhibitor, has been tested recently in a phase 2 study of patients with relapsing-remitting MS. The study met the primary endpoint of a significantly reduced cumulative number of Gadolinium-enhancing lesions under treatment with evobrutinib compared to placebo treatment. Thus, the results of ongoing phase 2 and 3 studies with evobrutinib, fenobrutinib, and tolebrutinib in relapsing-remitting and progressive MS are eagerly awaited. This review article introduces the physiological role of BTK, summarizes the pre-clinical and trial evidence, and addresses the potential beneficial effects of BTK inhibition in MS.
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http://dx.doi.org/10.2174/1381612827666210701152934DOI Listing
July 2021

Differential Effects of Psychological Interventions in Online and Face-to-Face Settings on DSM-5 and ICD-11 Maladaptive Trait Domains: An Exploratory Pilot Study.

Front Psychiatry 2021 14;12:648367. Epub 2021 Jun 14.

Division of Clinical Psychological Intervention, Department of Education and Psychology, Freie Universität Berlin, Berlin, Germany.

While mental health treatments have proven to be effective for a range of mental health problems, there is comparably little research on its effects on personality disorders or difficulty (PD). New dimensional conceptualizations of PD such as the ICD-11 PD model enable the cost- and time-effective dimensional assessment of severity and style of PD. Furthermore, they constitute a promising tool to investigate PD, not only as a treatment endpoint but also as a predictive or influencing factor for mental health treatments. In this study, we investigated the effects in two different mental health treatment settings [online ( = 38); face-to-face and blended [FTF/blended] ( = 35)] on the reduction of maladaptive personality traits as well as the interaction between maladaptive personality patterns and the response on primary endpoints (i.e., mental distress). Results indicate that both treatment settings have comparable within-group effects on the reduction of distress symptoms, while the treatment in the FTF/blended setting seems to have a stronger impact on the reduction of maladaptive traits. Further, reduction of maladaptive trait expressions was a reliable predictor of treatment response in the FTF/blended setting while explaining less variance in the online setting. Beyond the promising findings on the utility of maladaptive trait change as an outcome measure, we discuss possible applications as an information source for treatment decisions.
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http://dx.doi.org/10.3389/fpsyt.2021.648367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236509PMC
June 2021

Psychotherapeutic case formulation: Plan analysis for narcissistic personality disorder.

Personal Ment Health 2021 Jun 17. Epub 2021 Jun 17.

Institute of Psychotherapy, Department of Psychiatry, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Background: One of the relevant case formulation methods for personality difficulties is plan analysis. The present study aimed at delivering a prototypical plan analysis for clients presenting with a diagnosis of narcissistic personality disorder (NPD). The sample consisted of 14 participants diagnosed with an NPD. Based on audio clinical material, we developed 14 individual plan analyses that we then merged into a single prototypical plan analysis. For explorative purposes, we ran an ordinary least squares regression model to predict the narcissistic symptoms severity (NAR) measured on a scale of 1-7 of the 14 clients by the presence (respectively absence) of certain plans in their individual plan analysis. The synthesis revealed that clients with pathological narcissism share common basic motives. Results of the regression model reveal that the presence of the plan 'be strong' reduces the NAR scale by 1.52 points (p = 0.011).

Discussion: In the treatment of psychological disorders, precise case formulations allow therapists for making clinically appropriate decision, personalizing the intervention and gaining insight into the client's subjective experience. In the prototypical plan structure we developed for NPD, clients strive to strengthen their self-esteem and avoid loss of control, criticism and confrontation as well as to get support, understanding and solidarity. When beginning psychotherapy with a client presenting with NPD, the therapist can use these plans as valuable information to help writing tailored, and therefore more efficient, case formulations for their patients presenting with an NPD.
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http://dx.doi.org/10.1002/pmh.1521DOI Listing
June 2021

Differential Binding of Autoantibodies to MOG Isoforms in Inflammatory Demyelinating Diseases.

Neurol Neuroimmunol Neuroinflamm 2021 07 15;8(5). Epub 2021 Jun 15.

From the Clinical Department of Neurology (K.S., P.P., M.L., B.S., H.H., F.D.P., M.R.), Medical University of Innsbruck, Austria; Euroimmun Medizinische Labordiagnostika AG (S. Mindorf, N.R., C.P.), Lübeck, Germany; Institute for Quality Assurance (ifQ) affiliated to Euroimmun (M.P.), Lübeck, Germany; Department of Pediatrics (E.-M.W.), Olgahospital/Klinikum Stuttgart, Germany; Department of Pediatrics I (C.L., M.B.), Medical University of Innsbruck, Austria; Neurology Unit (S. Mariotto, S.F.), Department of Neuroscience, Biomedicine, and Movement Sciences, University of Verona, Italy; Neuroimmunology and Multiple Sclerosis Unit (A.S.), Service of Neurology, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Spain; Beaumont Hospital (M.F.), Dublin, Ireland; Oxford Autoimmune Neurology Group (M.I.S.L., S.R.I., J.P., P.W.), Nuffield Department of Clinical Neurosciences, University of Oxford, UK; Neuroimmunology and MS Research (A.L.), Department of Neurology, University Hospital Zurich & University of Zurich, Switzerland; Institute of Clinical Neuroimmunology (T.K.), Biomedical Center and University Hospital, Ludwig-Maximilians University, Munich, Germany; Department of Neurology (S.V., R.M.), Hospices civils de Lyon, Hôpital neurologique Pierre Wertheimer, France; Paediatric Neurology (K.R.), Witten/Herdecke University, Children's Hospital Datteln, Germany; Department of Neurology (T.B.), Medical University of Vienna, Austria; and Division of Neuropathology and Neurochemistry (R.H.), Department of Neurology, Medical University of Vienna, Austria.

Objective: To analyze serum immunoglobulin G (IgG) antibodies to major isoforms of myelin oligodendrocyte glycoprotein (MOG-alpha 1-3 and beta 1-3) in patients with inflammatory demyelinating diseases.

Methods: Retrospective case-control study using 378 serum samples from patients with multiple sclerosis (MS), patients with non-MS demyelinating disease, and healthy controls with MOG alpha-1-IgG positive (n = 202) or negative serostatus (n = 176). Samples were analyzed for their reactivity to human, mouse, and rat MOG isoforms with and without mutations in the extracellular MOG Ig domain (MOG-ecIgD), soluble MOG-ecIgD, and myelin from multiple species using live cell-based, tissue immunofluorescence assays and ELISA.

Results: The strongest IgG reactivities were directed against the longest MOG isoforms alpha-1 (the currently used standard test for MOG-IgG) and beta-1, whereas the other isoforms were less frequently recognized. Using principal component analysis, we identified 3 different binding patterns associated with non-MS disease: (1) isolated reactivity to MOG-alpha-1/beta-1 (n = 73), (2) binding to MOG-alpha-1/beta-1 and at least one other alpha, but no beta isoform (n = 64), and (3) reactivity to all 6 MOG isoforms (n = 65). The remaining samples were negative (n = 176) for MOG-IgG. These MOG isoform binding patterns were associated with a non-MS demyelinating disease, but there were no differences in clinical phenotypes or disease course. The 3 MOG isoform patterns had distinct immunologic characteristics such as differential binding to soluble MOG-ecIgD, sensitivity to MOG mutations, and binding to human MOG in ELISA.

Conclusions: The novel finding of differential MOG isoform binding patterns could inform future studies on the refinement of MOG-IgG assays and the pathophysiologic role of MOG-IgG.
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http://dx.doi.org/10.1212/NXI.0000000000001027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207634PMC
July 2021

Kurt Jellinger 90: his contribution to neuroimmunology.

J Neural Transm (Vienna) 2021 Jun 10. Epub 2021 Jun 10.

Department of Neurology, Medical University of Vienna, Vienna, Austria.

This review honors Kurt Jellinger on his 90th birthday as one of the most outstanding neuropathologists, who has contributed immensely to neuroscience due to his vast experience and collection of excellently documented autopsy cases. Two of his many insightful reports are highlighted here. One report focuses on the pathogenesis of inflammatory demyelinating diseases and investigates the neuropathology in autopsy tissue of a patient, who developed an MS-like disease after repeated treatment with lyophilized bovine brain cells in 1958. More than 60 years later, after reinvestigation of the historic samples in 2015 and subsequent mRNA isolation, next generation sequencing and reconstruction of the antibody, we succeeded in identifying myelin oligodendrocyte glycoprotein (MOG) as the target antigen and provided the missing element between the pathomechanisms in classic EAE animal models and transfer of this disease process into humans. A second significant example of Kurt Jellinger's contribution to neuroscience was a report on the role of MS in the development of Alzheimer's disease (AD), which found that AD pathology is present to the same extent in demyelinated and non-demyelinated cortical areas in MS and the incidence for AD pathology in elderly MS patients is comparable to the normal-aging population. This indicates that chronic inflammation in the MS cortex alone does not significantly predispose to the development of cortical AD pathology. These and other findings were only possible due to the broad collection of extremely well-defined material established by Kurt Jellinger, which ultimately continues to contribute to translational neuroscience, even decades later.
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http://dx.doi.org/10.1007/s00702-021-02358-4DOI Listing
June 2021

Functional Recovery in Autoimmune Encephalitis: A Prospective Observational Study.

Front Immunol 2021 21;12:641106. Epub 2021 May 21.

Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria.

Background: Prospective observations of functional recovery are lacking in patients with autoimmune encephalitis defined by antibodies against synaptic proteins and neuronal cell surface receptors.

Methods: Adult patients with a diagnosis of autoimmune encephalitis were included into a prospective registry. At 3, 6 and 12 months of follow-up, the patients' modified Rankin Scale (mRS) was obtained.

Results: Patients were stratified into three groups according to their antibody (Ab) status: anti-NMDAR-Ab (n=12; group I), anti-LGI1/CASPR2-Ab (n=35; group II), and other antibodies (n=24; group III). A comparably higher proportion of patients in group I received plasma exchange/immunoadsorption and second line immunosuppressive treatments at baseline. A higher proportion of patients in group II presented with seizures. Group III mainly included patients with anti-GABAR-, anti-GAD65- and anti-GlyR-Ab. At baseline, one third of them had cancer. Patients in groups I and III had much higher median mRS scores at 3 months compared to patients in group II. A median mRS of 1 was found at all follow-up time points in group II.

Conclusions: The different dynamics in the recovery of patients with certain autoimmune encephalitides have important implications for clinical trials. The high proportion of patients with significant disability at 3 months after diagnosis in groups I and III points to the need for improving treatment options. More distinct scores rather than the mRS are necessary to differentiate potential neurological improvements in patients with anti-LGI1-/CASPR2-encephalitis.
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http://dx.doi.org/10.3389/fimmu.2021.641106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175889PMC
May 2021

Kappa-Free Light Chains in CSF Predict Early Multiple Sclerosis Disease Activity.

Neurol Neuroimmunol Neuroinflamm 2021 07 28;8(4). Epub 2021 May 28.

From the Department of Neurology (K.B., M.A., F.D.P., A.Z., F.D., H.H.), Medical University of Innsbruck; Department of Neurology (G.B., T.B.), Medical University of Vienna; Department of Neuroradiology (A.G., P.P.), Medical University of Innsbruck; FH Campus Wien (D.M., C.S.), University of Applied Sciences, Vienna; Department of Neurology (S.W.), Medical University of Graz; and Department of Statistics (J.W.), Faculty of Economics and Statistics, University of Innsbruck, Austria.

Objective: To investigate whether κ-free light chain (κ-FLC) index predicts multiple sclerosis (MS) disease activity independent of demographics, clinical characteristics, and MRI findings.

Methods: Patients with early MS who had CSF and serum sampling at disease onset were followed for 4 years. At baseline, age, sex, type of symptoms, corticosteroid treatment, and number of T2 hyperintense (T2L) and contrast-enhancing T1 lesions (CELs) on MRI were determined. During follow-up, the occurrence of a second clinical attack and start of disease-modifying therapy (DMT) were registered. κ-FLCs were measured by nephelometry, and κ-FLC index calculated as [CSF κ-FLC/serum κ-FLC]/albumin quotient.

Results: A total of 88 patients at a mean age of 33 ± 10 years and female predominance of 68% were included; 38 (43%) patients experienced a second clinical attack during follow-up. In multivariate Cox regression analysis adjusting for age, sex, T2L, CEL, disease and follow-up duration, administration of corticosteroids at baseline and DMT during follow-up revealed that κ-FLC index predicts time to second clinical attack. Patients with κ-FLC index >100 (median value 147) at baseline had a twice as high probability for a second clinical attack within 12 months than patients with low κ-FLC index (median 28); within 24 months, the chance in patients with high κ-FLC index was 4 times as high as in patients with low κ-FLC index. The median time to second attack was 11 months in patients with high κ-FLC index whereas 36 months in those with low κ-FLC index.

Conclusion: High κ-FLC index predicts early MS disease activity.

Classification Of Evidence: This study provides Class II evidence that in patients with early MS, high κ-FLC index is an independent risk factor for early second clinical attack.
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http://dx.doi.org/10.1212/NXI.0000000000001005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168046PMC
July 2021

Seven day pre-analytical stability of serum and plasma neurofilament light chain.

Sci Rep 2021 May 26;11(1):11034. Epub 2021 May 26.

Department of Neurology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Neurofilament light chain (NfL) has emerged as a biomarker of neuroaxonal damage in several neurologic conditions. With increasing availability of fourth-generation immunoassays detecting NfL in blood, aspects of pre-analytical stability of this biomarker remain unanswered. This study investigated NfL concentrations in serum and plasma samples of 32 patients with neurological diagnoses using state of the art Simoa technology. We tested the effect of delayed freezing of up to 7 days and statistically determined stability and validity of measured concentrations. We found concentrations of NfL in serum and plasma to remain stable at room temperature when processing of samples is delayed up to 7 days (serum: mean absolute difference 0.9 pg/mL, intraindividual variation 1.2%; plasma: mean absolute difference 0.5 pg/mL, intraindividual variation 1.3%). Consistency of these results was nearly perfect for serum and excellent for plasma (intraclass correlation coefficients 0.99 and 0.94, respectively). In conclusion, the soluble serum and plasma NfL concentration remains stable when unprocessed blood samples are stored up to 7 days at room temperature. This information is essential for ensuring reliable study protocols, for example, when shipment of fresh samples is needed.
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http://dx.doi.org/10.1038/s41598-021-90639-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154890PMC
May 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

Multimodule Web-Based COVID-19 Anxiety and Stress Resilience Training (COAST): Single-Cohort Feasibility Study With First Responders.

JMIR Form Res 2021 Jun 7;5(6):e28055. Epub 2021 Jun 7.

Department of Psychiatry, Psychotherapy and Psychosomatics, University of Zurich, Zürich, Switzerland.

Background: Since the emergence of COVID-19, health care workers and first responders have been at a high risk for mental health symptoms owing to their exposure to the virus and increased work stress during the pandemic. Although interventions exist to address mental health issues following exposure to disasters, emergencies, and humanitarian crises, considerably less is known about web-based unguided interventions to help mitigate the negative impacts of such events. Additionally, in contexts in which emergencies reduce access to in-person care, remote forms of support are critical, yet there are limited studies on the use of such interventions. Evidence-based, easy-to-use, scalable interventions are direly needed for this population.

Objective: This study aimed to develop and test the feasibility of an unguided electronic mental health program, COVID-19 Anxiety and Stress Resilience Training (COAST), tailored to first responders and health care personnel, based on scientific evidence and empirically based techniques.

Methods: We developed COVID-19-specific training modules focusing on several domains that are previously reported as key to resilience and stress recovery: self-efficacy, mindfulness, sleep quality, and positive thinking. The program was made available to 702 first responders between May and August 2020, during the COVID-19 pandemic. Sociodemographic, work-, and COVID-19-related information was collected, and psychometric questionnaires were completed. We examined user acceptance and user activity, including module choice and participant feedback.

Results: In total, 52 of 702 (7%) first responders to whom we reached out used the program at least once. COAST use was independent of age, sex, or baseline levels of self-efficacy, mindful awareness, sleep quality, and positive thinking (for all, P>.39). First responders who had tested positive and those who had been quarantined were more likely to engage in the program. A click count analysis per module showed that participants used the self-efficacy and mindfulness modules most often, with 382 and 122 clicks, respectively, over 15 weeks. Overall, first responders expressed satisfaction with the program.

Conclusions: Engagement of first responders in the multimodule web-based COAST program was feasible and the first responder cohort expressed overall satisfaction with the program. Those in more difficult circumstances, including those in quarantine and those who tested positive, may be more likely to engage in such programs. Further controlled studies could pave the way for efficacy studies and the development of additional modules, including just-in-time interventions or blended interventions combining individual use of an unguided self-help intervention, such as COAST, with subsequent individual psychotherapy for those who continue to experience stress and psychological symptoms.
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http://dx.doi.org/10.2196/28055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189283PMC
June 2021

The Smartphone App haMSter for Tracking Patient-Reported Outcomes in People With Multiple Sclerosis: Protocol for a Pilot Study.

JMIR Res Protoc 2021 May 7;10(5):e25011. Epub 2021 May 7.

Department of Neurology, Medical University of Vienna, Vienna, Austria.

Background: Treatment and monitoring decisions in people with multiple sclerosis (MS) are based commonly on clinician-reported outcomes. These reflect physical and radiological disease activity and are the most relevant endpoints in clinical trials. Over the past few years, the number of studies evaluating so-called patient-reported outcomes (PROs) has been increasing. PROs are reports from patients concerning their own health perception. They are typically obtained by means of questionnaires and aim to quantify symptoms such as fatigue, depression, and sexual dysfunction. The emergence of PROs has made a tremendous contribution to understanding the individual impact of disease in people with MS and their health-related quality of life. However, the assessment of PROs consumes resources, including time and personnel. Thus, useful ways to conveniently introduce PROs into clinical practice are needed.

Objective: We aim to provide a rationale and pilot study protocol for a mobile health (mHealth) solution named "haMSter" that allows for remote monitoring of PROs in people with MS.

Methods: The core function of haMSter is to provide three scientifically validated PRO questionnaires relevant to MS for patients to fill out at home once a month. Thereby, longitudinal and remote documentation of PROs is enabled. A scoring algorithm graphically plots PRO scores over time and makes them available at the next visit.

Results: The pilot study is currently ongoing and will evaluate adherence to this mHealth solution in 50 patients over a period of 6 months. Results from the haMSter pilot study are expected in 2021.

Conclusions: haMSter is a novel mHealth-based solution for modern PRO research, which may constitute the first step in achieving the ability to integrate PROs in clinical practice. This allows for a more problem-oriented approach in monitoring visits, which addresses patient needs and ultimately saves time.

Trial Registration: ClinicalTrials.gov NCT04555863; https://clinicaltrials.gov/ct2/show/NCT04555863.

International Registered Report Identifier (irrid): DERR1-10.2196/25011.
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http://dx.doi.org/10.2196/25011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140378PMC
May 2021

Maintaining Outcomes of Internet-Delivered Cognitive-Behavioral Therapy for Depression: A Network Analysis of Follow-Up Effects.

Front Psychiatry 2021 20;12:598317. Epub 2021 Apr 20.

Department of Psychiatry, Lübeck University, Lübeck, Germany.

Depression is a highly prevalent mental disorder, but only a fraction of those affected receive evidence-based treatments. Recently, Internet-based interventions were introduced as an efficacious and cost-effective approach. However, even though depression is a heterogenous construct, effects of treatments have mostly been determined using aggregated symptom scores. This carries the risk of concealing important effects and working mechanisms of those treatments. In this study, we analyze outcome and long-term follow-up data from the EVIDENT study, a large ( = 1,013) randomized-controlled trial comparing an Internet intervention for depression (Deprexis) with care as usual. We use Network Intervention Analysis to examine the symptom-specific effects of the intervention. Using data from intermediary and long-term assessments that have been conducted over 36 months, we intend to reveal how the treatment effects unfold sequentially and are maintained. Item-level analysis showed that scale-level effects can be explained by small item-level effects on most depressive symptoms at all points of assessment. Higher scores on these items at baseline predicted overall symptom reduction throughout the whole assessment period. Network intervention analysis offered insights into potential working mechanisms: while deprexis directly affected certain symptoms of depression (e.g., worthlessness and fatigue) and certain aspects of the quality of life (e.g., overall impairment through emotional problems), other domains were affected indirectly (e.g., depressed mood and concentration as well as activity level). The configuration of direct and indirect effects replicates previous findings from another study examining the same intervention. Internet interventions for depression are not only effective in the short term, but also exert long-term effects. Their effects are likely to affect only a small subset of problems. Patients reporting these problems are likely to benefit more from the intervention. Future studies on online interventions should examine symptom-specific effects as they potentially reveal the potential of treatment tailoring. ClinicalTrials.gov, Identifier: NCT02178631.
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http://dx.doi.org/10.3389/fpsyt.2021.598317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8095668PMC
April 2021

Dismantling, optimising, and personalising internet cognitive behavioural therapy for depression: a systematic review and component network meta-analysis using individual participant data.

Lancet Psychiatry 2021 06 3;8(6):500-511. Epub 2021 May 3.

Department of Clinical Psychology, Faculty of Psychology, University of Bergen, Bergen, Norway.

Background: Internet cognitive behavioural therapy (iCBT) is a viable delivery format of CBT for depression. However, iCBT programmes include training in a wide array of cognitive and behavioural skills via different delivery methods, and it remains unclear which of these components are more efficacious and for whom.

Methods: We did a systematic review and individual participant data component network meta-analysis (cNMA) of iCBT trials for depression. We searched PubMed, PsycINFO, Embase, and the Cochrane Library for randomised controlled trials (RCTs) published from database inception to Jan 1, 2019, that compared any form of iCBT against another or a control condition in the acute treatment of adults (aged ≥18 years) with depression. Studies with inpatients or patients with bipolar depression were excluded. We sought individual participant data from the original authors. When these data were unavailable, we used aggregate data. Two independent researchers identified the included components. The primary outcome was depression severity, expressed as incremental mean difference (iMD) in the Patient Health Questionnaire-9 (PHQ-9) scores when a component is added to a treatment. We developed a web app that estimates relative efficacies between any two combinations of components, given baseline patient characteristics. This study is registered in PROSPERO, CRD42018104683.

Findings: We identified 76 RCTs, including 48 trials contributing individual participant data (11 704 participants) and 28 trials with aggregate data (6474 participants). The participants' weighted mean age was 42·0 years and 12 406 (71%) of 17 521 reported were women. There was suggestive evidence that behavioural activation might be beneficial (iMD -1·83 [95% credible interval (CrI) -2·90 to -0·80]) and that relaxation might be harmful (1·20 [95% CrI 0·17 to 2·27]). Baseline severity emerged as the strongest prognostic factor for endpoint depression. Combining human and automated encouragement reduced dropouts from treatment (incremental odds ratio, 0·32 [95% CrI 0·13 to 0·93]). The risk of bias was low for the randomisation process, missing outcome data, or selection of reported results in most of the included studies, uncertain for deviation from intended interventions, and high for measurement of outcomes. There was moderate to high heterogeneity among the studies and their components.

Interpretation: The individual patient data cNMA revealed potentially helpful, less helpful, or harmful components and delivery formats for iCBT packages. iCBT packages aiming to be effective and efficient might choose to include beneficial components and exclude ones that are potentially detrimental. Our web app can facilitate shared decision making by therapist and patient in choosing their preferred iCBT package.

Funding: Japan Society for the Promotion of Science.
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http://dx.doi.org/10.1016/S2215-0366(21)00077-8DOI Listing
June 2021

CANreduce 2.0 Adherence-Focused Guidance for Internet Self-Help Among Cannabis Users: Three-Arm Randomized Controlled Trial.

J Med Internet Res 2021 Apr 30;23(4):e27463. Epub 2021 Apr 30.

Swiss Research Institute for Public Health and Addiciton, University of Zurich, Zürich, Switzerland.

Background: Despite increasing demand for treatment among cannabis users in many countries, most users are not in treatment. Internet-based self-help offers an alternative for those hesitant to seek face-to-face therapy, though low effectiveness and adherence issues often arise.

Objective: Through adherence-focused guidance enhancement, we aimed to increase adherence to and the effectiveness of internet-based self-help among cannabis users.

Methods: From July 2016 to May 2019, cannabis users (n=775; male: 406/575, 70.6%, female: 169/575, 29.4%; age: mean 28.3 years) not in treatment were recruited from the general population and were randomly assigned to (1) an adherence-focused guidance enhancement internet-based self-help intervention with social presence, (2) a similar intervention with an impersonal service team, and (3) access to internet as usual. Controls who were placed on a waiting list for the full intervention after 3 months underwent an assessment and had access to internet as usual. The primary outcome measurement was cannabis-use days over the preceding 30 days. Secondary outcomes included cannabis-dependence severity, changes in common mental disorder symptoms, and intervention adherence. Differences between the study arms in primary and secondary continuous outcome variables at baseline, posttreatment, and follow-up were tested using pooled linear models.

Results: All groups exhibited reduced cannabis-use days after 3 months (social presence: -8.2 days; service team: -9.8 days; internet as usual: -4.2 days). The participants in the service team group (P=.01, d=.60) reported significantly fewer cannabis-use days than those in the internet as usual group; the reduction of cannabis use in the social presence group was not significant (P=.07, d=.40). There was no significant difference between the 2 intervention groups regarding cannabis-use reduction. The service team group also exhibited superior improvements in cannabis-use disorder, cannabis-dependence severity, and general anxiety symptoms after 3 months to those in the internet as usual group.

Conclusions: The adherence-focused guidance enhancement internet-based self-help intervention with an impersonal service team significantly reduced cannabis use, cannabis-use disorder, dependence severity, and general anxiety symptoms.

Trial Registration: ISRCTN Registry ISRCTN11086185; http://www.isrctn.com/ISRCTN11086185.
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http://dx.doi.org/10.2196/27463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122293PMC
April 2021

Impact of interfractional target motion in locally advanced cervical cancer patients treated with spot scanning proton therapy using an internal target volume strategy.

Phys Imaging Radiat Oncol 2021 Jan 6;17:84-90. Epub 2021 Feb 6.

Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.

Background And Purpose: The more localized dose deposition of proton therapy (PT) compared to photon therapy might allow a reduction in treatment-related side effects but induces additional challenges to address. The aim of this study was to evaluate the impact of interfractional motion on the target and organs at risk (OARs) in cervical cancer patients treated with spot scanning PT using an internal target volume (ITV) strategy.

Methods And Materials: For ten locally advanced cervical cancer patients, empty and full bladder planning computed tomography (pCT) as well as 25 daily cone beam CTs (CBCTs) were available. The Clinical Target Volume (CTV), the High Risk CTV (CTV) (gross tumor volume and whole cervix), the non-involved uterus as well as the OARs (bowel, bladder and rectum) were contoured on the daily CBCTs and transferred to the pCT through rigid bony match. Using synthetic CTs derived from pCTs, four-beam spot scanning PT plans were generated to target the patient-specific ITV with 45 Gy(RBE) in 25 fractions. This structure was defined based on pre-treatment MRI and CT to anticipate potential target motion throughout the treatment. D98% of the targets and V40Gy(RBE) of the OARs were extracted from the daily anatomies, accumulated and analyzed. In addition, the impact of bladder volume deviations from planning values on target and bowel dose was investigated.

Results: The ITV strategy ensured a total accumulated dose >42.75 Gy(RBE) to the CTV for all ten patients. Two patients with large bladder-related uterus motion had accumulated dose to the non-involved uterus of 35.7 Gy(RBE) and 41.1 Gy(RBE). Variations in bowel V40Gy(RBE) were found to be correlated (Pearson r = -0.55; p-value <0.0001) with changes in bladder volume during treatment.

Conclusion: The ITV concept ensured adequate dose to the CTV, but was insufficient for the non-involved uterus of patients subject to large target interfractional motion. CBCT monitoring and occasional replanning is recommended along the same lines as with photon radiotherapy in cervical cancer.
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http://dx.doi.org/10.1016/j.phro.2021.01.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058016PMC
January 2021

Long-term outcome and predictors of long-term disease activity in natalizumab-treated patients with multiple sclerosis: real life data from the Austrian MS Treatment Registry.

J Neurol 2021 Apr 22. Epub 2021 Apr 22.

Department of Neurology, Medical University of Vienna, Vienna, Austria.

Objectives: To evaluate long-term effectiveness of natalizumab (NTZ) and to determine demographic, clinical, and radiological predictors regarding long-term disease activity (≥ 7 years) in a nationwide observational cohort, using data collected prospectively in a real-life setting.

Materials And Methods: We analysed data from 230 patients from the Austrian Multiple Sclerosis Treatment Registry (AMSTR), who had started treatment with NTZ at any time since 2006 and stayed on NTZ for at least 7 years without treatment gap of more than three months.

Results: Estimated mean annualised relapse rates (ARR) over a mean treatment period of 9.3 years were 0.07 for NTZ. Sustained EDSS progression for 12 weeks was observed in 36 (19%) patients and for 24 weeks in 31 (16.3%) cases. Sustained EDSS regression for 12 and 24 weeks was seen in 45 (23.7%) and 42 (22.1%) cases. The baseline parameters ≥ 1 Gadolinium-enhancing MRI lesion(s) [incidence rate ratio (IRR) of 0.409 (95% CI 0.283-0.593), p = 0.001], ARR ≤ 1 in the prior 12 month before treatment initiation with NTZ [IRR of 0.353 (95% CI 0.200-0.623), p = 0.001] and EDSS ≤ 1 [incidence rate ratio (IRR) of 0.081 (95% CI 0.011-0.581), p = 0.012] were significantly associated with a reduced relapse risk, whereas a disease duration ≤ 5 years increased significantly the ARR [IRR of 1.851 (95% CI 1.249-2.743), p = 0.002]. The only predictive baseline parameter for experiencing EDSS progression (sustained for 12 and 24 weeks) was age > 35 years [HR of 2.482 (95% CI 1.110-5.549), p = 0.027, and HR of 2.492 (95% CI 1.039-5.978), p = 0.041, respectively].

Conclusions: These real-life data show a stable disease course regarding relapse activity and disease progression under NTZ treatment for more than 7 years. The main predictors for disease activity were higher relapse rate before treatment initiation, higher disability, shorter disease duration and absence of Gadolinium-enhancing MRI lesions at baseline. Older age at NTZ start was the only significant risk factor for disease progression over long-term.
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http://dx.doi.org/10.1007/s00415-021-10559-wDOI Listing
April 2021

Longitudinal CSF Findings in Autoimmune Encephalitis-A Monocentric Cohort Study.

Front Immunol 2021 22;12:646940. Epub 2021 Mar 22.

Department of Neurology, Medical University of Vienna, Vienna, Austria.

Autoimmune encephalitis (AIE) poses a diagnostic challenge due to its heterogeneous clinical presentation, which overlaps with various neurological and psychiatric diseases. During the diagnostic work-up, cerebrospinal fluid (CSF) is routinely obtained, allowing for differential diagnostics as well as for the determination of antibody subclasses and specificities. In this monocentric cohort study, we describe initial and serial CSF findings of 33 patients diagnosed with antibody-associated AIE (LGI1 (n=8), NMDA (n=7), CASPR2 (n=3), IgLON5 (n=3), AMPAR (n=1), GAD65/67 (n=4), Yo (n=3), Ma-1/2 (n=2), CV2 (n=2)). Routine CSF parameters of 12.1% of AIE patients were in normal ranges, while 60.6% showed elevated protein levels and 45.4% had intrathecal oligoclonal bands (OCBs). Repeated CSF analyses showed a trend towards normalization of initial pathological CSF findings, while relapses were more likely to be associated with increased cell counts and total protein levels. OCB status conversion in anti-NMDARE patients coincided with clinical improvement. In summary, we show that in routine CSF analysis at diagnosis, a considerable number of patients with AIE did not exhibit alteration in the CSF and therefore, diagnosis may be delayed if antibody testing is not performed. Moreover, OCB status in anti-NMDAR AIE patients could represent a potential prognostic biomarker, however further studies are necessary to validate these exploratory findings.
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http://dx.doi.org/10.3389/fimmu.2021.646940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019787PMC
March 2021

Restless Legs Syndrome in Multiple Sclerosis: Risk factors and effect on sleep quality - a case-control study.

Mult Scler Relat Disord 2021 Jun 21;51:102916. Epub 2021 Mar 21.

Department of Neurology, Medical University of Vienna, Vienna, Austria.

Introduction: Previous studies suggested an association between MS and Restless Legs Syndrome (RLS). Data on the prevalence of RLS in Austrian MS patients and on the influence of disease-modifying therapies (DMT) on RLS are lacking.

Objective: To investigate (1) the prevalence of RLS in Austria compared to control persons (CP), (2) risk factors for RLS in MS, and (3) influence of DMTs on RLS prevalence and/or severity.

Methods: Adult MS patients and CP were screened for RLS by face-to-face interviews, including questionnaires for RLS severity, sleep quality and daytime sleepiness.

Results: 23.9% of MS patients (n=117) had RLS compared to 3.4% (p<0.001) of CP (n=119). The MS+RLS group (n=28) had a higher rate of sleep impairment (78.6% vs 21.3%, p<0.001) and excessive daytime sleepiness (32.1% vs 15.7%, p=0.045) compared to the MS-RLS group. Multivariate regression analysis revealed higher Expanded Disability Status Scale and spinal lesions in MRI as risk factors for RLS in MS, while DMTs had no impact on RLS.

Conclusion: Roughly a quarter of MS patients suffers from RLS, significantly impacting quality of life by poor sleep quality and excessive daytime sleepiness. RLS risk increases with physical disability and spinal lesions but is independent of DMT.
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http://dx.doi.org/10.1016/j.msard.2021.102916DOI Listing
June 2021

Neurofilament light chain as a potential biomarker for monitoring neurodegeneration in X-linked adrenoleukodystrophy.

Nat Commun 2021 03 22;12(1):1816. Epub 2021 Mar 22.

Department of Pathobiology of the Nervous System, Center for Brain Research, Medical University of Vienna, Vienna, Austria.

X-linked adrenoleukodystrophy (X-ALD), the most frequent monogenetic disorder of brain white matter, is highly variable, ranging from slowly progressive adrenomyeloneuropathy (AMN) to life-threatening inflammatory brain demyelination (CALD). In this study involving 94 X-ALD patients and 55 controls, we tested whether plasma/serum neurofilament light chain protein (NfL) constitutes an early distinguishing biomarker. In AMN, we found moderately elevated NfL with increased levels reflecting higher grading of myelopathy-related disability. Intriguingly, NfL was a significant predictor to discriminate non-converting AMN from cohorts later developing CALD. In CALD, markedly amplified NfL levels reflected brain lesion severity. In rare cases, atypically low NfL revealed a previously unrecognized smoldering CALD disease course with slowly progressive myelin destruction. Upon halt of brain demyelination by hematopoietic stem cell transplantation, NfL gradually normalized. Together, our study reveals that blood NfL reflects inflammatory activity and progression in CALD patients, thus constituting a potential surrogate biomarker that may facilitate clinical decisions and therapeutic development.
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http://dx.doi.org/10.1038/s41467-021-22114-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985512PMC
March 2021

Sexuality and Multiple Sclerosis: Patient and Doctor Perspectives.

J Sex Med 2021 04 17;18(4):743-749. Epub 2021 Mar 17.

Medical University of Vienna, Department of Neurology, Vienna, Austria. Electronic address:

Background: Little is known on how to address sexuality in clinical care for patients with multiple sclerosis (pwMS).

Aim: To describe and contrast the perception of sexuality and associated aspects of communication in pwMS and their treating neurologists ("MSologists") and provide a standard of care.

Methods: Patients were surveyed using a 13-item questionnaire investigating perception on their own sexuality and opinions on communication about sexuality in context with MS. Certified MSologists in Austria received an 18-item survey regarding their approach to taking a sexual history of their patients.

Outcomes: We report the frequency of answers given in this survey and propose a possible standard of care how sexuality could be addressed in clinical routine.

Results: Ninety-three pwMS (mean age 39 ± 11 years, 57% female) and 75 MSologists (mean age 43 ± 9 years, 63% male) completed this survey. Seventy-six percent of patients report their own sexuality as being (very) important to them and 95% think that sexual dysfunction would influence their quality of life. 84% would like to be asked about their sexuality by their MSologist. In contrast, only 15% of MSologists reported discussing sexuality with every patient. The most common reason for not doing so was a fear of crossing personal borders (34%). There is a strong desire for further medical education on this subject (76%).

Clinical Implications: Discussing sexuality is important to pwMS and MSologists should consider their patients' wishes and needs to talk about it.

Strengths & Limitations: This is the largest survey contrasting the views of patients and their treating physicians on the topic of communication about sexuality. The use of an empirical unvalidated questionnaire may have introduced bias. Moreover, patients that are open to talk about their sexuality may be potentially overrepresented in this study.

Conclusion: MSologists should offer their patients an open opportunity and appropriate framework to discuss their sexuality during a consultation. Altmann P, Leithner K, Leutmezer F, et al. Sexuality and Multiple Sclerosis: Patient and Doctor Perspectives. J Sex Med 2021;18:743-749.
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http://dx.doi.org/10.1016/j.jsxm.2021.01.178DOI Listing
April 2021

Evaluation of Retinal Layer Thickness Parameters as Biomarkers in a Real-World Multiple Sclerosis Cohort.

Eye Brain 2021 12;13:59-69. Epub 2021 Mar 12.

Department of Neurology, Medical University of Vienna, Vienna, Austria.

Purpose: Retinal layer thickness parameters measured by optical coherence tomography (OCT) are emerging biomarkers of neuroaxonal degeneration and inflammation in multiple sclerosis (MS). We aimed to evaluate the value of retinal layer thickness for prediction of disability worsening and relapse in a real-world MS cohort.

Patients And Methods: For this longitudinal observational study, we included MS patients with spectral-domain OCT scans available and ≥1 year of clinical follow-up. The value of peripapillary retinal nerve fiber layer (pRNFL), macular ganglion-cell-and-inner-plexiform-layer (GCIPL) and inner nuclear layer (INL) thickness for prediction of disability worsening and relapse during the observation period was tested by multivariate models.

Results: We analyzed 60 MS patients during a mean observation period of 2.9 years (SD 1.8). Lower baseline thickness of GCIPL (cut-off <77µm; HR 4.1, p=0.001) and pRNFL (cut-off ≤88µm; HR 3.1, p=0.019) were associated with an increased risk of disability worsening. Longitudinally, mean thinning rates were -0.8µm/year (SD 1.6) for GCIPL, -0.6µm/year (SD 3.5) for pRNFL. GCIPL thinning ≥1.0µm/year and pRNFL >1.5µm/year is associated with higher likelihood of disability worsening (HR 5.7, p=0.009 and HR 6.8, p=0.003, respectively). INL thickened in patients with relapse by a mean 0.9µm while thinning by 0.3µm in patients without relapse (p=0.04). In multivariate analyses, INL thickening was associated with an increased probability of relapse (OR 17.8, p=0.023).

Conclusion: Cross-sectional and longitudinal measurement of GCIPL and pRNFL thinning is reliable as a biomarker of disability worsening in a real-world setting. Change of INL thickness is a promising marker of relapse, i.e. inflammatory activity.
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http://dx.doi.org/10.2147/EB.S295610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966301PMC
March 2021

Retinal layer thinning predicts treatment failure in relapsing multiple sclerosis.

Eur J Neurol 2021 Jun 2;28(6):2037-2045. Epub 2021 Apr 2.

Department of Neurology, Medical University of Vienna, Vienna, Austria.

Background And Purpose: Peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell plus inner plexiform layer (GCIPL) thinning are markers of neuroaxonal degeneration in multiple sclerosis (MS), which is reduced by disease-modifying treatment (DMT). We aimed to investigate the potential of pRNFL and GCIPL thinning for prediction of DMT failure in relapsing MS (RMS).

Methods: In this 4-year prospective observational study on 113 RMS patients, pRNFL and GCIPL were measured at DMT initiation and after 12 months (M12) and 24 months (M24). Treatment failure was defined as 6-month confirmed Expanded Disability Status Scale (EDSS) progression and/or Symbol Digit Modalities Test (SDMT) worsening. Optimal cutoff values for predicting treatment failure were determined by receiver operating characteristic analyses and hazard ratios (HRs) by multivariable Cox regression adjusting for age, sex, disease duration, EDSS/SDMT, and DMT class.

Results: Thinning of GCIPL >0.5 μm/year at M24 showed superior value for treatment failure prediction (HR: 4.5, 95% confidence interval [CI]: 1.8-7.6, p < 0.001; specificity 91%, sensitivity 81%), followed by GCIPL >0.5 μm at M12 (odds ratio [OR]: 3.9, 95% CI: 1.4-6.9, p < 0.001; specificity 85%, sensitivity 78%), and pRNFL ≥2 μm/year at M24 (OR: 3.7, 95% CI: 1.1-6.5, p = 0.023; specificity 84%, sensitivity 69%), whereas pRNFL at M12 was not predictive.

Conclusions: GCIPL, and to a lesser degree pRNFL, thinning predicts disability progression after DMT initiation and may be a useful and accessible biomarker of treatment failure in RMS.
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http://dx.doi.org/10.1111/ene.14829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251588PMC
June 2021