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So far, only the detection of 14-3-3 proteins in cerebrospinal fluid (CSF) has been accepted as diagnostic criterion for Creutzfeldt-Jakob disease (CJD). However, this assay cannot be used for screening because of the high rate of false-positive results, whereas patients with variant CJD are often negative for 14-3-3 proteins. The aim of this study was to compare the spot patterns of CSF by 2-dimensional polyacrylamide gel electrophoresis (2D-PAGE) to search for a CJD-specific spot pattern. We analyzed the CSF of 28 patients [11 CJD, 9 Alzheimer's disease (AD), 8 nondemented controls (NDC)] employing 2D-PAGE which was optimized for minimal volumes of CSF (0.1 ml; 7-cm strips). All samples were run at least three times, gels were silver stained and analyzed by an analysis software and manually revised. We could consistently match 268 spots which were then compared between all groups. By the use of 5 spots, we were able to differentiate CJD from AD or NDC with a sensitivity of 100%. CJD could also be distinguished from both groups by using a heuristic clustering algorithm of 2 spots. We conclude that this proteomic approach can differentiate CJD from other diseases and may serve as a model for other neurodegenerative diseases. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Cladribine tablets for the treatment of relapsing multiple sclerosis (RMS) are administered in two pulsed treatment courses in two consecutive years, totalling a maximum of 20 treatment days. Here we present data collected shortly after the launch of cladribine tablets, focusing on the patient's perspective. The objective was to investigate patients' perceived effectiveness, tolerability, and convenience, as well as global satisfaction of and with cladribine tablets., Methods: CLEVER was a non-interventional multicentre study conducted in Germany from 12/2017 to 7/2020. Adult patients with RMS initiating therapy with cladribine tablets were included. Observation time per patient was 24 weeks, comprising 3 visits (baseline, week 4 and 24). The primary endpoint was overall treatment satisfaction at week 24, assessed by the Treatment Satisfaction Questionnaire for Medication 14 items (TSQM 1.4). Subgroup analyses included stratification by prior treatment., Results: In total, 491 patients (69.2 % female; mean (±SD) age 40.3 (±11.5) years, 85.1 % pre-treated, median EDSS 2.5) initiated therapy with cladribine tablets and were included in the analysis. At week 24, the mean (±SD) global TSQM satisfaction score was 75.6 (±19.0). For patients switching from either injectables or oral medication, the change in therapy satisfaction from baseline to week 24 was positive in all TSQM domains with clinically meaningful effect sizes in the global satisfaction and side effects domains. Most patients (85.5 %) remained relapse-free over 24 weeks. Out of 491 patients, 187 (38.1 %) experienced at least one adverse event and 8 patients (1.6 %) one serious adverse event., Conclusion: Treatment satisfaction with cladribine tablets was high. The switch from prior injectables or oral medication translated into increased treatment satisfaction at week 24 with clinically meaningful effects in the global satisfaction and side effects domains. Effectiveness and safety were consistent with results from clinical studies., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tjalf Ziemssen reports financial support was provided by Merck Healthcare Germany GmbH. Tjalf Ziemssen reports a relationship with Almirall that includes: consulting or advisory and speaking and lecture fees. Tjalf Ziemssen reports a relationship with Bayer Pharma that includes: consulting or advisory and speaking and lecture fees. Tjalf Ziemssen reports a relationship with Biogen that includes: consulting or advisory, funding grants, and speaking and lecture fees. Tjalf Ziemssen reports a relationship with Celgene that includes: consulting or advisory and speaking and lecture fees. Tjalf Ziemssen reports a relationship with Sanofi-Genzyme that includes: consulting or advisory, funding grants, and speaking and lecture fees. Tjalf Ziemssen reports a relationship with Merck that includes: consulting or advisory and speaking and lecture fees. Tjalf Ziemssen reports a relationship with Novartis that includes: consulting or advisory, funding grants, and speaking and lecture fees. Tjalf Ziemssen reports a relationship with Roche that includes: consulting or advisory and speaking and lecture fees. Tjalf Ziemssen reports a relationship with Teva that includes: consulting or advisory, funding grants, and speaking and lecture fees. Anita Posevitz-Fejfár reports a relationship with Merck Healthcare Germany GmbH that includes: employment. Anita Chudecka reports a relationship with Cytel Inc that includes: employment. Lukas Cepek reports a relationship with Almirall that includes: consulting or advisory, funding grants, and speaking and lecture fees. Lukas Cepek reports a relationship with Bayer that includes: consulting or advisory, funding grants, and speaking and lecture fees. Lukas Cepek reports a relationship with Biogen Idec that includes: consulting or advisory, funding grants, and speaking and lecture fees. Lukas Cepek reports a relationship with BMS that includes: consulting or advisory, funding grants, and speaking and lecture fees. Lukas Cepek reports a relationship with Celgene that includes: consulting or advisory, funding grants, and speaking and lecture fees. Lukas Cepek reports a relationship with Mylan that includes: consulting or advisory, funding grants, and speaking and lecture fees. Lukas Cepek reports a relationship with Genzyme -Sanofi that includes: consulting or advisory, funding grants, and speaking and lecture fees. Lukas Cepek reports a relationship with Merck that includes: consulting or advisory, funding grants, and speaking and lecture fees. Lukas Cepek reports a relationship with Novartis that includes: consulting or advisory, funding grants, and speaking and lecture fees. Lukas Cepek reports a relationship with Teva that includes: consulting or advisory, funding grants, and speaking and lecture fees. Lukas Cepek reports a relationship with Roche that includes: consulting or advisory, funding grants, and speaking and lecture fees. Lukas Cepek reports a relationship with Zambon that includes: consulting or advisory, funding grants, and speaking and lecture fees. Gerd Reifschneider reports a relationship with Merck that includes: consulting or advisory, funding grants, and speaking and lecture fees. Gerd Reifschneider reports a relationship with Biogen that includes: consulting or advisory, funding grants, and speaking and lecture fees. Gerd Reifschneider reports a relationship with Novartis that includes: consulting or advisory, funding grants, and speaking and lecture fees. Gerd Reifschneider reports a relationship with Sanofi that includes: consulting or advisory, funding grants, and speaking and lecture fees. Gerd Reifschneider reports a relationship with Genzyme that includes: consulting or advisory, funding grants, and speaking and lecture fees. Gerd Reifschneider reports a relationship with Sanofi Aventis that includes: consulting or advisory, funding grants, and speaking and lecture fees. Gerd Reifschneider reports a relationship with Roche that includes: consulting or advisory, funding grants, and speaking and lecture fees. Gerd Reifschneider reports a relationship with UCB that includes: consulting or advisory, funding grants, and speaking and lecture fees. Gerd Reifschneider reports a relationship with Destin that includes: consulting or advisory, funding grants, and speaking and lecture fees. Gerd Reifschneider reports a relationship with Health HERZ Economics Research Zentrum that includes: consulting or advisory, funding grants, and speaking and lecture fees. Gerd Reifschneider reports a relationship with Hexal that includes: consulting or advisory, funding grants, and speaking and lecture fees. Gerd Reifschneider reports a relationship with Hormosan that includes: consulting or advisory, funding grants, and speaking and lecture fees. Gerd Reifschneider reports a relationship with Med Day that includes: consulting or advisory, funding grants, and speaking and lecture fees. Christoph Grothe reports a relationship with Biogen that includes: consulting or advisory, speaking and lecture fees, and travel reimbursement. Christoph Grothe reports a relationship with Merck that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Christoph Grothe reports a relationship with Novartis that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Christoph Grothe reports a relationship with Sanofi that includes: consulting or advisory, speaking and lecture fees, and travel reimbursement. Christoph Grothe reports a relationship with Roche that includes: consulting or advisory, speaking and lecture fees, and travel reimbursement. Christoph Grothe reports a relationship with Boehringer Ingelheim that includes: consulting or advisory, speaking and lecture fees, and travel reimbursement. Christoph Grothe reports a relationship with Teva that includes: consulting or advisory, speaking and lecture fees, and travel reimbursement. Joachim Richter reports a relationship with Merck Healthcare Germany GmbH that includes: employment. Torsten Wagner reports a relationship with Merck Healthcare Germany GmbH that includes: employment. Beate Müller reports a relationship with Merck Healthcare Germany GmbH that includes: employment. Iris-Katharina Penner reports a relationship with Adamas Pharma that includes: consulting or advisory and speaking and lecture fees. Iris-Katharina Penner reports a relationship with Almirall that includes: consulting or advisory and speaking and lecture fees. Iris-Katharina Penner reports a relationship with Bayer Pharma that includes: consulting or advisory and speaking and lecture fees. Iris-Katharina Penner reports a relationship with Biogen that includes: consulting or advisory and speaking and lecture fees. Iris-Katharina Penner reports a relationship with Celgene that includes: consulting or advisory, funding grants, and speaking and lecture fees. Iris-Katharina Penner reports a relationship with Desitin that includes: consulting or advisory and speaking and lecture fees. Iris-Katharina Penner reports a relationship with Sanofi-Genzyme that includes: consulting or advisory and speaking and lecture fees. Iris-Katharina Penner reports a relationship with Janssen that includes: consulting or advisory and speaking and lecture fees. Iris-Katharina Penner reports a relationship with Merck Healthcare Germany GmbH that includes: consulting or advisory and speaking and lecture fees. Iris-Katharina Penner reports a relationship with Novartis that includes: consulting or advisory, funding grants, and speaking and lecture fees. Iris-Katharina Penner reports a relationship with Roche that includes: consulting or advisory, funding grants, and speaking and lecture fees. Iris-Katharina Penner reports a relationship with Teva that includes: consulting or advisory, funding grants, and speaking and lecture fees. Iris-Katharina Penner reports a relationship with German MS Society that includes: funding grants., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The current approval of oral cladribine covers four years, with two treatment courses in the first two years, followed by two treatment-free years. For decision-making in year 5, experts recommend three scenarios: Extending the treatment-free period, retreatment with cladribine, or therapy switch., Objective: To assess the implementation of the three year-5-scenarios in clinical practice in a large multicentric real-world cohort in Germany., Methods: Data from adult patients diagnosed with highly active RMS (first dose between 8/2017 and 8/2018) were included. The primary outcome was the percentages of patients who remained treatment-free in year 5, were retreated with cladribine, or switched to another therapy., Results: In total, 187 patients (75 % female, mean age 38.6 years, median EDSS 2.5, 21 % DMT-naive) were evaluated. Overall, 27 (14 %) switched treatment within year 1-4, 36 (19 %) continued therapy with cladribine tablets in year 5, and 8 (4 %) switched therapy in year 5. All other patients (n = 118, 63 %) continued to be monitored without therapy in year 5., Conclusion: The recommended three treatment scenarios in year 5 appear to be feasible in clinical practice. Treatment-free structured monitoring is the most frequently applied strategy, highly likely due to the prospect of continuing low disease activity under cladribine treatment., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Markus C. Kowarik reports financial support was provided by Merck. Markus C. Kowarik reports a relationship with Merck that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Markus C. Kowarik reports a relationship with Sanofi-Genzyme that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Markus C. Kowarik reports a relationship with Novartis that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Markus C. Kowarik reports a relationship with Biogen that includes: consulting or advisory, speaking and lecture fees, and travel reimbursement. Markus C. Kowarik reports a relationship with Janssen that includes: consulting or advisory, speaking and lecture fees, and travel reimbursement. Markus C. Kowarik reports a relationship with Alexion that includes: consulting or advisory, speaking and lecture fees, and travel reimbursement. Markus C. Kowarik reports a relationship with Celgene Bristol-Myers Squibb that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Markus C. Kowarik reports a relationship with Roche that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Michael Ernst reports financial support was provided by Merck. Michael Ernst reports a relationship with Merck that includes: consulting or advisory, speaking and lecture fees, and travel reimbursement. Michael Ernst reports a relationship with Sanofi-Genzyme that includes: consulting or advisory, speaking and lecture fees, and travel reimbursement. Michael Ernst reports a relationship with Novartis that includes: consulting or advisory, speaking and lecture fees, and travel reimbursement. Michael Ernst reports a relationship with Biogen that includes: consulting or advisory, speaking and lecture fees, and travel reimbursement. Michael Ernst reports a relationship with Alexion that includes: consulting or advisory, speaking and lecture fees, and travel reimbursement. Michael Ernst reports a relationship with Celgene Bristol-Myers Squibb that includes: consulting or advisory, speaking and lecture fees, and travel reimbursement. Michael Ernst reports a relationship with Roche that includes: consulting or advisory, speaking and lecture fees, and travel reimbursement. Lara Woitschach reports financial support was provided by Merck. Lukas Cepek reports financial support was provided by Merck. Lukas Cepek reports a relationship with Merck that includes: consulting or advisory and speaking and lecture fees. Lukas Cepek reports a relationship with Bayer Pharma that includes: consulting or advisory and speaking and lecture fees. Lukas Cepek reports a relationship with Biogen that includes: consulting or advisory and speaking and lecture fees. Lukas Cepek reports a relationship with Celgene that includes: consulting or advisory and speaking and lecture fees. Lukas Cepek reports a relationship with Eli Lilly and Company that includes: consulting or advisory and speaking and lecture fees. Lukas Cepek reports a relationship with Genzyme that includes: consulting or advisory and speaking and lecture fees. Lukas Cepek reports a relationship with Novartis that includes: consulting or advisory and speaking and lecture fees. Lukas Cepek reports a relationship with Roche that includes: consulting or advisory and speaking and lecture fees. Lukas Cepek reports a relationship with Teva that includes: consulting or advisory and speaking and lecture fees. Daniela Rau reports financial support was provided by Merck. Daniela Rau reports a relationship with Merck that includes: consulting or advisory and speaking and lecture fees. Daniela Rau reports a relationship with Bayer Pharma that includes: consulting or advisory and speaking and lecture fees. Daniela Rau reports a relationship with Biogen that includes: consulting or advisory and speaking and lecture fees. Daniela Rau reports a relationship with Celgene that includes: consulting or advisory and speaking and lecture fees. Daniela Rau reports a relationship with Eli Lilly and Company that includes: consulting or advisory and speaking and lecture fees. Daniela Rau reports a relationship with Genzyme that includes: consulting or advisory and speaking and lecture fees. Daniela Rau reports a relationship with Hexal that includes: consulting or advisory and speaking and lecture fees. Daniela Rau reports a relationship with Novartis that includes: consulting or advisory, funding grants, and speaking and lecture fees. Daniela Rau reports a relationship with Roche that includes: consulting or advisory and speaking and lecture fees. Daniela Rau reports a relationship with Teva that includes: consulting or advisory and speaking and lecture fees. Benedicta Kühnler reports financial support was provided by Merck. Benedicta Kühnler reports a relationship with Merck that includes: consulting or advisory and speaking and lecture fees. Benedicta Kühnler reports a relationship with Biogen that includes: consulting or advisory and speaking and lecture fees. Benedicta Kühnler reports a relationship with Novartis that includes: consulting or advisory and speaking and lecture fees. Benedicta Kühnler reports a relationship with Roche that includes: consulting or advisory and speaking and lecture fees. Benedicta Kühnler reports a relationship with Sanofi-Aventis that includes: consulting or advisory and speaking and lecture fees. Benedicta Kühnler reports a relationship with Teva that includes: consulting or advisory and speaking and lecture fees. Sylke Schlemilch-Paschen reports financial support was provided by Merck. Sylke Schlemilch-Paschen reports a relationship with Novartis that includes: speaking and lecture fees. Sylke Schlemilch-Paschen reports a relationship with Merck that includes: speaking and lecture fees. Sylke Schlemilch-Paschen reports a relationship with Biogen that includes: consulting or advisory and speaking and lecture fees. Sylke Schlemilch-Paschen reports a relationship with BMS that includes: speaking and lecture fees. Sylke Schlemilch-Paschen reports a relationship with Sanofi that includes: consulting or advisory and speaking and lecture fees. Sylke Schlemilch-Paschen reports a relationship with Roche that includes: consulting or advisory. Christoph Grothe reports financial support was provided by Merck. Christoph Grothe reports a relationship with Merck that includes: consulting or advisory. Christoph Grothe reports a relationship with Biogen that includes: consulting or advisory. Christoph Grothe reports a relationship with Boehringer Ingelheim that includes: consulting or advisory. Christoph Grothe reports a relationship with Janssen that includes: consulting or advisory. Christoph Grothe reports a relationship with Novartis that includes: consulting or advisory and funding grants. Christoph Grothe reports a relationship with Sanofi, Roche that includes: consulting or advisory. Christoph Grothe reports a relationship with Teva that includes: consulting or advisory. Matthias Schwab reports financial support was provided by Merck. Matthias Schwab reports a relationship with Merck that includes: consulting or advisory, speaking and lecture fees, and travel reimbursement. Matthias Schwab reports a relationship with Actelion-Janssen that includes: consulting or advisory, speaking and lecture fees, and travel reimbursement. Matthias Schwab reports a relationship with Almirall that includes: consulting or advisory, speaking and lecture fees, and travel reimbursement. Matthias Schwab reports a relationship with Bayer that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Matthias Schwab reports a relationship with Biogen that includes: consulting or advisory, speaking and lecture fees, and travel reimbursement. Matthias Schwab reports a relationship with Bristol Myers Squibb that includes: consulting or advisory, speaking and lecture fees, and travel reimbursement. Matthias Schwab reports a relationship with Celgene that includes: consulting or advisory, speaking and lecture fees, and travel reimbursement. Matthias Schwab reports a relationship with Hexal that includes: consulting or advisory, speaking and lecture fees, and travel reimbursement. Matthias Schwab reports a relationship with Novartis that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Matthias Schwab reports a relationship with Roche that includes: consulting or advisory, speaking and lecture fees, and travel reimbursement. Matthias Schwab reports a relationship with Sanofi Genzyme that includes: consulting or advisory, speaking and lecture fees, and travel reimbursement. Matthias Schwab reports a relationship with Teva that includes: consulting or advisory, speaking and lecture fees, and travel reimbursement. Petra Jöstingmeyer reports financial support was provided by Merck. Christoph Kleinschnitz reports financial support was provided by Merck. Christoph Kleinschnitz reports a relationship with Merck that includes: speaking and lecture fees and travel reimbursement. Christoph Kleinschnitz reports a relationship with Alexion that includes: speaking and lecture fees and travel reimbursement. Christoph Kleinschnitz reports a relationship with Almirall that includes: speaking and lecture fees and travel reimbursement. Christoph Kleinschnitz reports a relationship with AstraZenica that includes: speaking and lecture fees and travel reimbursement. Christoph Kleinschnitz reports a relationship with Bayer that includes: speaking and lecture fees and travel reimbursement. Christoph Kleinschnitz reports a relationship with Biogen that includes: speaking and lecture fees and travel reimbursement. Christoph Kleinschnitz reports a relationship with Biontech that includes: speaking and lecture fees and travel reimbursement. Christoph Kleinschnitz reports a relationship with Boehringer Ingelheim that includes: speaking and lecture fees and travel reimbursement. Christoph Kleinschnitz reports a relationship with Bristol Myers-Squibb that includes: speaking and lecture fees and travel reimbursement. Christoph Kleinschnitz reports a relationship with C.T.I. that includes: speaking and lecture fees and travel reimbursement. Christoph Kleinschnitz reports a relationship with Daiichi Sankyo that includes: speaking and lecture fees and travel reimbursement. Christoph Kleinschnitz reports a relationship with Docspert that includes: speaking and lecture fees and travel reimbursement. Christoph Kleinschnitz reports a relationship with Mylan Viatris that includes: speaking and lecture fees and travel reimbursement. Christoph Kleinschnitz reports a relationship with Novartis that includes: speaking and lecture fees and travel reimbursement. Christoph Kleinschnitz reports a relationship with Pfizer that includes: speaking and lecture fees and travel reimbursement. Christoph Kleinschnitz reports a relationship with Roche that includes: speaking and lecture fees and travel reimbursement. Christoph Kleinschnitz reports a relationship with Sanofi-Aventis that includes: speaking and lecture fees and travel reimbursement. Christoph Kleinschnitz reports a relationship with Stada that includes: speaking and lecture fees and travel reimbursement. Christoph Kleinschnitz reports a relationship with Teva that includes: speaking and lecture fees and travel reimbursement. Christoph Kleinschnitz reports a relationship with Janssen-Cilag that includes: speaking and lecture fees and travel reimbursement. Christoph Kleinschnitz reports a relationship with Horizon Therapeutics that includes: speaking and lecture fees and travel reimbursement. Christoph Kleinschnitz reports a relationship with Medscape LLC that includes: speaking and lecture fees and travel reimbursement. Christoph Kleinschnitz reports a relationship with Baumgart Consultants that includes: speaking and lecture fees and travel reimbursement. Christoph Kleinschnitz reports a relationship with StreamedUp! that includes: speaking and lecture fees and travel reimbursement. Christoph Kleinschnitz reports a relationship with Hexal Sandoz that includes: speaking and lecture fees and travel reimbursement. Christoph Kleinschnitz reports a relationship with Agentur Süss that includes: speaking and lecture fees and travel reimbursement. Christoph Kleinschnitz reports a relationship with Viatris that includes: speaking and lecture fees and travel reimbursement. Refik Pul reports financial support was provided by Merck. Refik Pul reports a relationship with Merck that includes: consulting or advisory, funding grants, and speaking and lecture fees. Refik Pul reports a relationship with Alexion that includes: consulting or advisory and speaking and lecture fees. Refik Pul reports a relationship with Bayer Healthcare that includes: consulting or advisory and speaking and lecture fees. Refik Pul reports a relationship with Biogen that includes: consulting or advisory and speaking and lecture fees. Refik Pul reports a relationship with Bristol Myers Squibb Celgene that includes: consulting or advisory and speaking and lecture fees. Refik Pul reports a relationship with Horizon that includes: consulting or advisory and speaking and lecture fees. Refik Pul reports a relationship with Mylan that includes: consulting or advisory and speaking and lecture fees. Refik Pul reports a relationship with Novartis that includes: consulting or advisory, funding grants, and speaking and lecture fees. Refik Pul reports a relationship with Roche that includes: consulting or advisory and speaking and lecture fees. Refik Pul reports a relationship with Sanofi Genzyme that includes: consulting or advisory and speaking and lecture fees. Refik Pul reports a relationship with Teva that includes: funding grants., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Interferon beta (IFN beta) preparations are an established group of drugs used for immunomodulation in patients with multiple sclerosis (MS). Subcutaneously (sc) applied interferon beta-1a (IFN beta-1a sc) has been in continuous clinical use for 25 years as a disease-modifying treatment., Areas Covered: Based on data published since 2018, we discuss recent insights from analyses of the pivotal trial PRISMS and its long-term extension as well as from newer randomized studies with IFN beta-1a sc as the reference treatment, the use of IFN beta-1a sc across the patient life span and as a bridging therapy, recent data regarding the mechanisms of action, and potential benefits of IFN beta-1a sc regarding vaccine responses., Expert Opinion: IFN beta-1a sc paved the way to effective immunomodulatory treatment of MS, enabled meaningful insights into the disease process, and remains a valid therapeutic option in selected vulnerable MS patient groups.

Background: Many female people with multiple sclerosis (pwMS) are in childbearing age; however, only few data exist about the situation of breastfeeding in pwMS. Objective: Our study analyzed breastfeeding rate and duration, reasons for weaning, and the impact of disease severity on successful breastfeeding in pwMS. Methods: The study included pwMS giving birth within 3 years before study participation. Data were collected by structured questionnaire. Results: Compared to published data, we found a significant difference ( p  = 0.0007) between the nursing rate in the general population (96.6%) and females with MS (85.9%). However, a higher rate of exclusive breastfeeding could be observed in our study population for 5-6 months in 40.6% of pwMS versus 9% for 6 months in the general population. In contrast, total breastfeeding duration in our study population was shorter (18.8% for 11-12 months) than in the general population (41.1% for 12 months). Reasons for weaning were predominantly (68.7%) related to breastfeeding barriers based on MS. No significant impact of prepartum or postpartum education on the breastfeeding rate could be observed. Prepartum relapse rate and prepartum disease-modifying drugs had no effect on breastfeeding success. Conclusion: Our survey provides an insight into the situation of breastfeeding in pwMS in Germany.

Despite improvements in diagnosis and treatment, multiple sclerosis (MS) is the leading neurological cause of disability in young adults. As a chronic disease, MS requires complex and challenging management. In this context, eHealth has gained an increasing relevance. Here, we aim to summarize beneficial features of a mobile app recently implemented in clinical MS routine as well as beyond MS. PatientConcept is a CE-certified, ID-associated multilingual software application allowing patients to record relevant health data without disclosing any identifying data. Patients can voluntarily share their health data with selected physicians. Since its implementation in 2018, about 3000 MS patients have used PatientConcept. Initially developed as a physician-patient communication platform, the app maps risk management plans of all current disease modifying therapies and thereby facilitates adherence to specified monitoring appointments. It also allows continuous monitoring of various PROs (Patient Reported Outcomes), enabling a broad overview of the disease course. In addition, various studies/projects currently assess monitoring, follow-up, diagnostics and telemetric evaluations of patients with other diseases beyond MS. Altogether, PatientConcept offers a broad range of possibilities to support physician-patient communication, implementation of risk management plans and assessment of PROs. It is a promising tool to facilitate patient-tailored management of MS and other chronic diseases.

Introduction: In addition to a wide range of disease-related burdens, patients with multiple sclerosis (MS) are challenged by long-term medication and complex disease management plans, often leading to decreased adherence. Earlier studies have indicated that patient support through intensified communication can positively impact adherence. During recent years, the use of mobile health applications has gained importance in patient communication and disease management., Objective: Our objective was to describe a novel software application providing innovative features that engage patient-physician contact and to evaluate users' acceptance., Methods: A novel software application ensuring data security was developed. Various innovative modules have been implemented, enabling bidirectional communication between treating physicians and patients, supporting therapy monitoring and management, and allowing the collection of large sets of anonymous patient data. The currently conducted FASTER study will analyze the acceptance of patients and physicians using this novel application., Results: PatientConcept is a free app available for download since 2016. Meanwhile, it has been successfully implemented. First preliminary results indicate high acceptance among users. The clinical benefit will have to be tested in larger patient populations., Conclusion: This ID-associated application may provide a secure, feasible, and cost-optimized possibility to intensify and simplify the communication between patients and their treating physicians, thus promising an exceptional benefit to both.

Background: The discrimination of bacterial meningitis (BM) versus viral meningitis (VM) shapes up as a problem, when laboratory data are not equivocal, in particular, when Gram stain is negative., Methodology/principal Findings: With the aim to determine reliable marker for bacterial or viral meningitis, we subjected cerebrospinal fluid (CSF) to a quantitative proteomic screening. By using a recently established 2D-DIGE protocol which was adapted to the individual CSF flow, we compared a small set of patients with proven BM and VM. Thereby, we identified six potential biomarkers out of which Prostaglandin-H2 D-isomerase was already described in BM, showing proof of concept. In the subsequent validation phase on a more comprehensive collective of 80 patients, we could validate that in BM high levels of glial fibrillary acidic protein (GFAP) and low levels of soluble amyloid precursor protein alpha/beta (sAPPalpha/beta) are present as possible binding partner of Fibulin-1., Conclusions/significance: We conclude that our CSF flow-adapted 2D-DIGE protocol is valid especially in comparing samples with high differences in total protein and suppose that GFAP and sAPPalpha/beta have a high potential as additional diagnostic markers for differentiation of BM from VM. In the clinical setting, this might lead to an improved early diagnosis and to an individual therapy.

Glial fibrillary acidic protein (GFAP) and protein S-100B are established indicators of astrogliosis in neuropathology. As GFAP and S-100B are expressed in different cell populations, variable cerebrospinal fluid (CSF) concentrations of these proteins might reflect disease-specific pathological profiles. Therefore we investigated CSF of patients with Alzheimer's disease (AD), patients with Creutzfeldt-Jakob disease (CJD), and non-demented control patients (CON). Measurement of GFAP and S-100B in CSF was performed by commercially available ELISA. Our results show that, in AD, there are significantly higher levels of GFAP concentrations, compared to CON (p = 0.001) and CJD patients (p = 0.009), whereas S-100B is much higher in CJD, compared to AD (p = 0.001) and CON (p = 0.001). In conclusion, GFAP and S-100B represent astroglial markers and the different levels of these proteins in CSF of AD and CJD patients might point to a distinct pathophysiological involvement in these diseases. Apart from pathophysiological aspects, GFAP in particular might serve as an additional diagnostic tool for AD, due to the fact that this protein does not correlate to established markers like tau and amyloid-beta such that analysis of GFAP may be useful for further differential diagnostic approaches in neurodegenerative diseases.

So far only the detection of 14-3-3 proteins in cerebrospinal fluid (CSF) is included in the diagnostic criteria for sporadic Creutzfeldt-Jakob disease (sCJD). However, this assay cannot be used for screening because of the high rate of false positive results in sCJD, and often negative results in variant CJD. To facilitate the differential diagnosis of CJD, we applied 2-D differential gel-electrophoresis (2-D DIGE) as a quantitative proteomic screening system for CSF proteins. We compared 36 patients suffering from sCJD with 30 patients suffering from other neurodegenerative diseases. Sample preparation was optimized in consideration of the fact that CSF is composed of blood- and brain-derived proteins, and an improved 2-D DIGE protocol was established. Using this method in combination with protein identification by MALDI-TOF-MS, several known surrogate markers of sCJD like 14-3-3 protein, neuron-specific enolase, and lactate dehydrogenase were readily identified. Moreover, a not yet identified protein with an approximate molecular mass of 85 kDa was found as marker for sCJD with high diagnostic specificity and sensitivity. We conclude that our proteomic approach is useful to differentiate CJD from other neurodegenerative diseases and expect that CSF-optimized 2-D DIGE will find broad application in the search for other brain derived proteins in CSF.

So far, only the detection of 14-3-3 proteins in cerebrospinal fluid (CSF) has been accepted as diagnostic criterion for Creutzfeldt-Jakob disease (CJD). However, this assay cannot be used for screening because of the high rate of false-positive results, whereas patients with variant CJD are often negative for 14-3-3 proteins. The aim of this study was to compare the spot patterns of CSF by 2-dimensional polyacrylamide gel electrophoresis (2D-PAGE) to search for a CJD-specific spot pattern. We analyzed the CSF of 28 patients [11 CJD, 9 Alzheimer's disease (AD), 8 nondemented controls (NDC)] employing 2D-PAGE which was optimized for minimal volumes of CSF (0.1 ml; 7-cm strips). All samples were run at least three times, gels were silver stained and analyzed by an analysis software and manually revised. We could consistently match 268 spots which were then compared between all groups. By the use of 5 spots, we were able to differentiate CJD from AD or NDC with a sensitivity of 100%. CJD could also be distinguished from both groups by using a heuristic clustering algorithm of 2 spots. We conclude that this proteomic approach can differentiate CJD from other diseases and may serve as a model for other neurodegenerative diseases., (Copyright 2007 S. Karger AG, Basel)

We describe a patient who experienced a fatal ipsilateral basal ganglia hemorrhage within an hour after carotid angioplasty and stent placement. In the few similar cases published there were no prodromata, but hyperacute onset of severe neurologic deterioration corresponding to intracerebral hemorrhage (ICH). Our findings suggest that besides the delayed ICH that is associated with hyperperfusion syndrome (HPS), a second type of hyperacute and usually fatal ICH exists that resembles hypertensive hemorrhage.

To study the potential diagnostic value of abnormally phosphorylated tau protein in Creutzfeldt-Jakob disease (CJD) compared to Alzheimer's disease (AD), we determined levels of tau phosphorylated at threonine 231 (p-tau231) and of total tau (t-tau) in cerebrospinal fluid (CSF) of CJD patients, AD patients, and healthy controls (HC). CJD patients showed excessively high t-tau levels but relatively low p-tau(231) concentrations compared to the AD group. t-tau alone yielded the best diagnostic accuracy to differentiate between CJD and AD patients, when compared to p-tau231 and the p-tau231/t-tau ratio (97, 78, and 95% correctly allocated cases, respectively). Our findings indicate a dissociation in the direction of change in CSF levels of t-tau and p-tau231 in CJD when compared to AD.

Background: S-100B and tau protein have a high differential diagnostic potential for the diagnosis of Creutzfeldt-Jakob disease (CJD). So far there has been only limited information available about the dynamics of these parameters in the cerebrospinal fluid (CSF). However, there is a special interest in finding biochemical markers to monitor disease progression for differential diagnosis and treatment., Patients and Methods: We analyzed CSF of 45 patients with CJD and of 45 patients with other neurological diseases for tau protein and S-100B in a follow-up setting. All diagnoses of CJD were later neuropathologically verified. A ratio between tau protein differences and the time between lumbar puncture was calculated. The same was done for S-100B., Results: Tau protein levels of 34 cases were above the cut-off level for CJD (>1,300 pg/ml) in the first CSF sample. In 7 of 11 patients with lower tau levels in the first CSF sample, tau levels rose. The above-mentioned ratio was significantly higher in the CJD group than in the group with other neurological diseases. Similar results were obtained for S-100B., Conclusion: We conclude that follow-up investigations and calculation of ratios is a useful tool in the differential diagnosis of CJD. Variations in this pattern were observed in single cases.

The diagnosis of neurodegenerative diseases with dementias requires several different test approaches and often remains uncertain. Using a proteomic approach it was shown in nine patients that heart fatty acid binding protein (H-FABP) might be a biomarker for Creutzfeldt-Jakob disease (CJD). The aim of our study was to evaluate whether H-FABP is a biomarker for the differential diagnosis of dementias. Therefore we measured H-FABP in cerebrospinal fluid (CSF) and serum of patients having CJD, dementia with Lewy-bodies (DLB), Alzheimer's disease (AD) and in non-demented control (NDC) patients. H-FABP levels in CSF and serum of CJD patients are increased compared to non-demented controls. Levels of H-FABP were significantly higher in CJD patients compared to AD and DLB in CSF. However, discrimination between CJD and AD was not possible in serum. Interestingly, highest levels of H-FABP were found in serum of DLB patients. Our results suggest that H-FABP might be a useful biomarker for the differentiation between the dementias examined if levels in CSF and serum are determined in parallel.

A quantitative urea-based amyloid beta (Abeta)-sodium dodecyl sulfate-polyacrylamide gel electrophoresis with Western immunoblot (Abeta-SDS-PAGE/immunoblot) reveals highly conserved and disease-specific Abeta peptide patterns (Abeta 1-37, 1-38, 1-39, 1-40, 1-42) in Alzheimer's disease (AD) patients and nondemented controls. For further standardization of this method, we analyzed cerebrospinal fluid (CSF) of eight probable AD patients and seven nondemented controls using different preanalytical procedures for Abeta-SDS-PAGE/immunoblot and Abeta1-42-enzyme linked immunosorbent assay (ELISA). Both diagnostic groups were discriminated significantly by absolute levels of Abeta1-42 and ratios of Abeta1-42/40, 1-42/38, 1-42/39. Preanalytical freezing of CSF led to a highly significant loss of all Abeta peptide species. This effect was most pronounced for Abeta1-42 and completely prevented by SDS-heat denaturation prior to freezing. Prolonged storage of SDS-heat denatured CSF led to a selective loss of Abeta1-42 and impaired the discrimination of diagnostic groups as measured by Abeta-SDS-PAGE/immunoblot. Neither freezing nor storage significantly affected absolute Abeta1-42 levels as determined by Abeta1-42-ELISA, but both impaired the discrimination of diagnostic groups. Hence, we suggest immediate analysis of samples for Abeta1-42-ELISA, analysis after a short freezing interval for Abeta-SDS-PAGE/immunoblot, and avoidance of prolonged storage intervals. Remarkably, Abeta-SDS-PAGE/immunoblot measured threefold higher levels of Abeta1-42 in CSF than Abeta1-42-ELISA. In summary, our results indicate carrier-mediated epitope masking of Abeta1-42.

Decreased levels of beta-amyloid peptide 1-42 (Abeta1-42) in cerebrospinal fluid (CSF) are a characteristic feature of Alzheimer's disease (AD) but recently were also observed in Creutzfeldt-Jakob disease (CJD). We analyzed the CSF of patients with CJD, and AD and nondemented controls using a quantitative urea-based Abeta sodium dodecyl sulfate polyacrylamide gel electrophoresis immunoblot. Like in AD and nondemented controls, we found a highly conserved pattern of carboxyterminally truncated Abeta1-37/38/39 in addition to Abeta1-40/42 also in CJD patients. By the introduction of the ratio Abeta1-39 to Abeta1-42, CJD and AD can effectively be differentiated. We conclude that the immunoblot shows disease-specific CSF Abeta peptide patterns in CJD and AD and suppose that measurement of the Abeta peptide pattern seems to be a promising diagnostic tool in the differential diagnosis of dementias.

In Creutzfeldt-Jakob disease (CJD), progressive neuronal cell death probably occurs as a result of a change in conformation of the physiological prion protein (PrP(C)). There is evidence of participation of the lymphatic system and in particular of lymphocytes in the intracorporeal transportation of the pathological prion protein (PrP(Sc)) in new variant CJD and scrapie. Using fluorescence cytometry, we investigated a possible alteration of PrP(C) on lymphocytes of patients with sporadic CJD. We demonstrated a significantly lower binding pattern of antibodies (3F4) against physiological prion protein to lymphocytes of patients with sporadic CJD (n=16) compared with control patients. In contrast this difference was not found on platelets (n=23). For the first time we were able to present a measurable difference of antibody binding on lymphocytes of patients with CJD. One interpretation of this finding is that lymphocytes patrolling the brain bind and transport PrP(Sc) which has a lower binding affinity for the antibodies directed against physiological PrP.

Background: Erythropoietin (EPO) and its receptor play a major role in embryonic brain, are weakly expressed in normal postnatal/adult brain and up-regulated upon metabolic stress. EPO protects neurons from hypoxic/ ischemic injury. The objective of this trial is to study the safety and efficacy of recombinant human EPO (rhEPO) for treatment of ischemic stroke in man., Materials and Methods: The trial consisted of a safety part and an efficacy part. In the safety study, 13 patients received rhEPO intravenously (3.3 X 10(4) IU/50 ml/30 min) once daily for the first 3 days after stroke. In the double-blind randomized proof-of-concept trial, 40 patients received either rhEPO or saline. Inclusion criteria were age <80 years, ischemic stroke within the middle cerebral artery territory confirmed by diffusion-weighted MRI, symptom onset <8 hr before drug administration, and deficits on stroke scales. The study endpoints were functional outcome at day 30 (Barthel Index, modified Rankin scale), NIH and Scandinavian stroke scales, evolution of infarct size (sequential MRI evaluation using diffusion-weighted [DWI] and fluid-attenuated inversion recovery sequences [FLAIR]) and the damage marker S100ss., Results: No safety concerns were identified. Cerebrospinal fluid EPO increased to 60-100 times that of nontreated patients, proving that intravenously administered rhEPO reaches the brain. In the efficacy trial, patients received rhEPO within 5 hr of onset of symptoms (median, range 2:40-7:55). Admission neurologic scores and serum S100beta concentrations were strong predictors ofoutcome. Analysis of covariance controlled for these two variables indicated that rhEPO treatment was associated with an improvement in follow-up and outcome scales. A strong trend for reduction in infarct size in rhEPO patients as compared to controls was observed by MRI., Conclusion: Intravenous high-dose rhEPO is well tolerated in acute ischemic stroke and associated with an improvement in clinical outcome at 1 month. A larger scale clinical trial is warranted.

Biochemical markers of brain damage, e.g. ischemic stroke, should reflect the volume of irreversibly damaged brain parenchyma and the clinical outcome in a single patient in order to allow estimation of prognosis at an early stage. Tau protein, which derives predominantly from neurons and axons, is elevated in the cerebrospinal fluid of patients with neurodegenerative disease. This makes tau protein a potential marker of neuronal/axonal injury. In order to test this hypothesis, the current study aimed at showing that tau protein is measurable in the blood after acute ischemic stroke and that it correlates with clinical disability and stroke volume. In a longitudinal prospective study we measured tau protein serum levels with an ELISA in 30 patients longitudinally after ischemic stroke. Tau protein was detectable within 5 days after ischemia in the sera of 7/20 patients with MRI-proven infarction and in 2/10 patients with transitory ischemic attack; both of them had a small infarction visible on the MRI scan. Tau protein was measurable within 6 h after symptom onset, peaked after 3-5 days and correlated with infarct volume and disability after 3 months. In conclusion, serum tau protein is a candidate marker of axonal injury. In stroke, its clinical use is limited, because it is detectable only in a proportion of patients., (Copyright 2002 S. Karger AG, Basel)

Creutzfeldt-Jakob disease (CJD) belongs to the group of transmissible spongiform encephalopathies. It is suspected that a pathologically altered form of the prion protein (PrPSc) is the decisive trigger of the disease. Data from animal experiments suggest an involvement of the lymphatic system in the intracorporal transport of PrPSc. However, it has not so far been possible to detect PrPSc on mononuclear cells (MNCs) either in the sporadic form of CJD or in the new variant of CJD (vCJD). In order to determine a possible alteration of MNCs in CJD, we investigated the natural and induced apoptotic behaviour of these cells. MNCs from 19 patients with sporadic CJD and from 20 patients with other neurological disorders were used. The cells were analysed by fluorescence cytometry with and without apoptosis induction by xanthine oxidase and hypoxanthine. The apoptosis rate was quantified using the stain 7-amino-actinomycin D (7-AAD). In the morphological investigation of the cells before apoptosis induction, there were no significant differences between the groups with regard to cell size and granularity of the MNCs. After apoptosis induction, the typical significant decrease in cell size and increase in granularity of the cells occurred in both groups. Significant differences between the patient populations were not found. For the first time, our investigation has demonstrated that a functional impairment of MNCs with regard to their apoptotic behaviour does not occur in sporadic CJD. It remains open to question whether this mechanism plays an important role in forms of transmissible encephalopathy other than sporadic CJD, especially after oral transmission.