David Ellenberger

• Analyst at MS Forschungs- und Projektentwicklungs-gGmbH

Importance A growing body of literature suggests the presence of a prodromal period with nonspecific signs and symptoms before onset of multiple sclerosis (MS). Objective To systematically assess diseases and symptoms diagnosed in the 5 years before a first MS- or central nervous system (CNS) demyelinating disease–related diagnostic code in pediat...

In pre‐clinical and medical quality control, it is of interest to assess the stability of the process under monitoring or to validate a current observation using historical control data. Classically, this is done by the application of historical control limits (HCL) graphically displayed in control charts. In many applications, HCL are applied to c...

Background The spectrum of disease-modifying therapies (DMTs) for people with multiple sclerosis (PwMS) has expanded over years, but data on treatment strategies is largely lacking. DMT switches are common clinical practice. Objective To compare switchers and non-switchers, characterize the first DMT switch and identify reasons and predictors for...

Background Persons with MS (PwMS) ≥ 55 years are underrepresented in therapy studies leading to a lack of evidence. Objective and methods To study the subgroup of PwMS ≥ 55 years in the German MS registry in comparison with PwMS < 55 years. Endpoints of interest were the grade of disability, leading symptoms, clinical and magnetic resonance imagin...

Background Treatment guidelines recommend early disease-modifying therapy (DMT) initiation after diagnosis of multiple sclerosis (MS). Multinational comparative studies that assess time to DMT initiation in MS may allow detection of barriers inherent to healthcare systems to explain potential adverse systematic delays in commencing DMTs. Objective...

Several studies reported post-SARS-CoV-2-vaccination (PV) symptoms. Even people with multiple sclerosis (PwMS) have concerns about disease activity following the SARS-CoV-2 vaccination. We aimed to determine the proportion of PwMS with PV relapses, the PV annualized relapse rate (ARR), the time from vaccination to subsequent relapses, and identify...

Background Epileptic seizures can occur throughout the course of multiple sclerosis (MS) and are associated with increasing disability progression over time. However, there are no data on whether epileptic seizures at the onset of MS also lead to increasing disability. Objective To examine disease progression over time for MS patients with epilept...

Introduction: Prescribing guidance for disease-modifying treatment (DMT) in multiple sclerosis (MS) is centred on a clinical diagnosis of relapsing-remitting MS (RRMS). DMT prescription guidelines and monitoring vary across countries. Standardising the approach to diagnosis of disease course, for example, assigning RRMS or secondary progressive MS...

Monitoring of clinical trials is a fundamental process required by regulatory agencies. It assures the compliance of a center to the required regulations and the trial protocol. Traditionally, monitoring teams relied on extensive on-site visits and source data verification. However, this is costly, and the outcome is limited. Thus, central statisti...

Despite protection from severe COVID-19 courses through vaccinations, some people with multiple sclerosis (PwMS) are vaccination-hesitant due to fear of post-vaccination side effects/increased disease activity. The aim was to reveal the frequency and predictors of post-SARS-CoV-2-vaccination relapses in PwMS. This prospective, observational study w...

Background To assign a course of secondary progressive multiple sclerosis (MS) (SPMS) may be difficult and the proportion of persons with SPMS varies between reports. An objective method for disease course classification may give a better estimation of the relative proportions of relapsing–remitting MS (RRMS) and SPMS and may identify situations wh...

Background : The aim of this study was to evaluate how many MS patients treated with an approved DMD in routine care would have fulfilled the inclusion and exclusion criteria of phase III clinical trial and would therefore be eligible for the respective drug trial. Further, adverse events and disease progression for these patients were compared. M...

Background: Vaccines offer people with multiple sclerosis (PwMS) an effective protection against severe COVID-19 disease courses. However, representative real-world data on the tolerability of SARS-CoV-2 vaccines in PwMS are limited. We aimed at analysing vaccination reactions (VRs) and MS deterioration following SARS-CoV-2 vaccinations in German...

Background People with Multiple Sclerosis (PwMS) suffer from an increased risk of unemployment during the course of the disease. In recent years progress has been made in increasing the time until patients have to leave the workforce permanently. Such a retirement is often associated with MS but the driving factors including disability progression,...

Background: This study aimed to describe recent developments of multiple sclerosis (MS) prevalence in Germany and to assess utilization patterns of disease-modifying drugs (DMDs). Methods: We used nationwide outpatient claims data of the statutory health insurance (SHI) from the years 2012 to 2019, covering 87% of the total German population. In an...

Introductions: Therapy switches in patients with multiple sclerosis (MS) receiving treatment with fingolimod occur frequently in clinical practice but are not well represented in real-world data. The aim of this study was to identify and characterize treatment switches and reveal sociodemographic/clinical changes over time in fingolimod-treated peo...

Background: The manifestation of multiple sclerosis (MS) in childhood and adolescence occurs in 3%−5% of all MS cases. However, the immunomodulatory and symptomatic treatment options in this population group are still limited. Objective: We aimed to elucidate the prescription frequency of medications used in pediatric patients with multiple scleros...

Background Epilepsy development during the course of multiple sclerosis (MS) is considered to be the result of cortical pathology. However, no long-term data exist on whether epilepsy in MS also leads to increasing disability over time. Objective To examine if epilepsy leads to more rapid disease progression. Methods We analyzed the data of 31,05...

Background: The tailored immunomodulatory treatment strategy for secondary progressive multiple sclerosis (SPMS) depends on disease activity. Objective: To assess the real-world situation in monitoring disease activity in SPMS patients and to identify associations of resulting subgroups with demographics, symptomatology, and therapy Methods: This s...

Objective To investigate the time to diagnosis in multiple sclerosis (MS) in Germany. Methods Analysis of real-world registry data from the German Multiple Sclerosis Registry (GMSR) and performing a primary analysis in patients where month-specific registration of the dates of onset and diagnosis was available. Results As of January 2020, data of...

Background: Prevalence data are needed to reveal trends regarding the pediatric multiple sclerosis (MS) situation worldwide. The aim was to identify changes in MS diagnosis prevalence in pediatric patients over a 10-year period in Germany. Methods: This analysis is based on nationwide outpatient claims data of children aged <18 years covered by...

In 2001, the German Multiple Sclerosis Society, facing lack of data, founded the German MS Registry (GMSR) as a long-term data repository for MS healthcare research. By the establishment of a network of participating neurological centres of different healthcare sectors across Germany, GMSR provides observational real-world data on long-term disease...

Automatic passenger counting (APC) in public transport has been introduced in the 1970s and has been rapidly emerging in recent years. APC systems, like all other measurement devices, are susceptible to error, which is treated as random noise and is required to not exceed certain bounds. The demand for very low errors is especially fueld by applica...

Background Newly approved, drug-modifying therapies are associated with still unknown adverse events, although clinical trials leading to approval have strict inclusion and exclusion criteria and analyse safety and efficacy. Objectives The aim of this study was to analyse the eligibility of multiple sclerosis (MS) patients treated in routine care...

Automatic passenger counting (APC) in public transport has been introduced in the 1970s and has been rapidly emerging in recent years. Still, real-world applications continue to face events that are difficult to classify. The induced imprecision needs to be handled as statistical noise and thus methods have been defined to ensure that measurement e...

To detect a change in the probability of a sequence of independent binomial random variables, a variety of asymptotic and exact testing procedures have been proposed. Whenever the sample size or the event rate is small, asymptotic approximations of maximally selected test statistics have been shown to be inaccurate. Although exact methods control t...

Zusammenfassung Einleitung Unter Federführung der Deutschen Multiple Sklerose Gesellschaft (DMSG), Bundesverband e. V. wurde 2001 ein bundesweites MS-Register initiiert, um epidemiologische Daten zur MS, deren Verlaufsformen und der Versorgungssituation in Deutschland zu erheben. Das Ziel der vorliegenden Auswertung war es, die Daten der letzten Au...

Background Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease whose aetiology is not fully understood. The female sex is clearly predominant, with a sex ratio between 2 and 3. In primary progressive MS the sex ratio almost balances out. Since the age at onset is higher for patients with progressive onset (POMS) than for relaps...

Daclizumab was approved by the FDA and the EMA in 2016 for the treatment of relapsing forms of multiple sclerosis (MS). Cases of severe inflammatory brain disease with fatal outcome led to the withdrawal of approval in Europe and the US on March 2, 2018. Approximately 8,000 patients worldwide received daclizumab, but little is known about the furth...

Background: Multiple sclerosis (MS) is a neuroinflammatory and neurodegenerative disease with an unpredictable course that has a broad clinical spectrum and progresses over time. If a person with MS (PwMS) shows overall mild to moderate disability even after a long duration of disease, the term benign MS (BMS) is used. However, there is currently...

Zusammenfassung Einleitung Unter Federführung der Deutschen Multiple Sklerose Gesellschaft (DMSG), Bundesverband e. V. wurde 2001 ein bundesweites MS-Register initiiert, um epidemiologische Daten zur MS, deren Verlaufsformen und der Versorgungssituation in Deutschland zu erheben. Das Ziel der vorliegenden Auswertung war es, die Daten der letzten Au...

Objective To assess the feasibility of collaboration and retrospective data harmonization among three multiple sclerosis (MS) registries by investigating employment status. Methods We used the Maelstrom guidelines to facilitate retrospective harmonization of data from three MS registries, including the NARCOMS (North American Research Committee on...

Early active multiple sclerosis (MS) lesions can be classified histologically into three main immunopathological patterns of demyelination (patterns I–III), which suggest pathogenic heterogeneity and may predict therapy response. Patterns I and II show signs of immune-mediated demyelination, but only pattern II is associated with antibody/complemen...

Importance Obesity reportedly increases the risk of pediatric multiple sclerosis (MS), but little is known about its association with disease course. Objective To investigate the association of obesity with pediatric MS risk and with first-line therapy response among children with MS. Design, Setting, and Participants This single-center retrospec...

Background Multiple sclerosis (MS) is a neuroinflammatory and neurodegenerative disease. Over time, symptoms accumulate leading to increased disability of patients. Objective The objective of this article is to analyze the prevalence of symptoms and symptomatic treatment patterns in a nationwide MS registry. Methods Data sets from 35,755 patients...

Rationale Central venous catheter (CVC) placement is a standard procedure in critical care. Ultrasound guidance during placement is recommended by current guidelines, but there is no consensus on the best method for evaluating the correct CVC tip position. Recently, the “rapid atrial swirl sign” (RASS) has been investigated in a limited number of s...

Standard reporting in diagnostic accuracy studies (STARD) checklist. (DOCX)

Sample size estimation. (DOCX)

Study protocol, English. (PDF)

Study protocol, German. (PDF)

Highlights • Glucocorticosteroid (GCS) continuous to decrease in Germany. • Natalizumab utilization decreased with the emergence of additional treatment options. • GCS utilization decreases for both RRMS and SPMS. • The generally observed decrease in relapses per year is confirmed with in the data.

Aims: In heart failure, enhanced persistent Na+ current (INaL) exerts detrimental effects on cellular electrophysiology and can induce arrhythmias. However, the underlying regulatory mechanisms remain unclear. Our aim was to potentially investigate the regulation and electrophysiological contribution of neuronal sodium channel Nav1.8 in failing hu...

Automatic passenger counting (APC) in public transport has been introduced in the 1970s and has been rapidly emerging in recent years. Still, real-world applications continue to face events that are difficult to classify. The induced imprecision needs to be handled as statistical noise and thus methods have been defined to ensure that measurement e...

Importance Plasma exchange and immunoadsorption are second-line apheresis therapies for patients experiencing multiple sclerosis relapses. Early active multiple sclerosis lesions can be classified into different histopathological patterns of demyelination. Pattern 1 and 2 lesions show T-cell– and macrophage–associated demyelination, and pattern 2 i...

Objective Study aims were to determine the frequency of highly active disease in pediatric multiple sclerosis (MS), the response to natalizumab (NTZ) and fingolimod (FTY) treatment, and the impact of current treatment modalities on the clinical course. Methods Retrospective single-center study in the German Center for MS in Childhood and Adolescen...

Background Microhematuria (MH) is a symptom frequently leading to uncertainty as to when a nephrology referral is appropriate. Because MH may be indicative of severe kidney disorders, prompt diagnosis and potential treatment initiation can be important. We aimed to identify further variables that point at a nephrological cause, in particular of glo...

Objectives: Methods for change point (also sometimes referred to as threshold or breakpoint) detection in binary sequences are not new and were introduced as early as 1955. Much of the research in this area has focussed on asymptotic and exact conditional methods. Here we develop an exact unconditional test. Methods: An unconditional exact test...

Objective: To assess in an observational study whether serum peptide antibody reactivities may distinguish aquaporin-4 (AQP4) antibody (Ab)-positive and -negative neuromyelitis optica spectrum disorders (NMOSD) and relapsing-remitting multiple sclerosis (RRMS). Methods: We screened 8,700 peptides that included human and viral antigens of potenti...

Aims Clinical studies have shown differences in the propensity for malignant ventricular arrhythmias between women and men suffering from cardiomyopathies and heart failure (HF). This is clinically relevant as it impacts therapies like prophylactic implantable cardioverter-defibrillator implantation but the pathomechanisms are unknown. As an increa...

Sealant application during fixed appliances orthodontic treatment for enamel protection is common, however, reliable data on its durability in vivo are rare. This study aims at assessing the durability of a sealant (OpalSeal, Ultradent) for protection against white-spot lesion formation in orthodontic patients over 26 weeks in vivo, taking into acc...

Multiple Sclerosis is the most common disease in young adults affecting the central nervous system. Disease will progress with acute attacks (relapsing MS) our continuously (progressive MS). Glucocorticosteroids are used in the treatment of acute attacks. The aim of this study is to analyze characteristics of MS patients and their influence on curr...

Background Identification of MS registries and databases that are currently in use in Europe as well as a detailed knowledge of their content and structure is important in order to facilitate comprehensive analysis and comparison of data. Methods National MS registries or databases were identified by literature search, from the results of the MS B...

Thymic neuroendocrine tumors (TNET) are rare primary epithelial neoplasms of the thymus. This study aimed to determine clinically relevant parameters for their classification and for therapeutic decisions. We performed a comprehensive histological, clinical, and genetic study of 73 TNET cases (13 thymic typical carcinoids [TTC], 40 thymic atypical...

Background Because of the emergence of novel therapies for multiple sclerosis (MS) and the associated increased risk of progressive multifocal leukoencephalopathy, John Cunningham (JC) virus infection has become a focus of interest for neurologists. However, little is known about JC virus infection in pediatric MS to date. Objective We aimed to an...

Suction ability plays an important role in supporting oral nutrition and needs special care following neurological disorders and tumor-associated defects. However, the details of suction are still poorly understood. The present study evaluates displacement of orofacial structures during suction and deglutition based on manometric controlled MRI. Ni...

Multiple sclerosis (MS) onset before puberty is extremely rare and establishment of diagnosis is often difficult due to atypical presentation. The study aims to identify the typical presentation of MS in this age group. Pediatric MS patients were identified from the database of the Center for Multiple Sclerosis in Childhood and Adolescence at the U...

AKI significantly worsens prognosis of hospitalized patients. This is particularly the case in patients with sepsis. The risk for aquiring sepsis is significantly increased in malignant diseases. Aim of the present retrospective study was to analyze outcomes of tumor patients with sepsis and AKI. One-thousand and seventeen patients, treated at the...

Background/aims: In adults, plasma exchange (PE) has been shown to be an efficient treatment for severe relapses of acute inflammatory CNS demyelinating diseases. The aim of this study was to evaluate the safety and efficacy of this treatment in pediatric patients. Methods: We retrospectively analyzed a single-center cohort of pediatric patients...

Sarcoplasmatic reticulum (SR) Ca(2+)-leak through ryanodine receptor type 2 (RyR2) dysfunction is of major pathophysiological relevance in human heart failure (HF). However, mechanisms underlying progressive RyR2 dysregulation from cardiac hypertrophy (Hy) to HF are still controversial. We investigated healthy control myocardium (NF, n=5) as well a...

Objectives Persons with multiple sclerosis (PwMS) experience health-related quality of life (HRQoL) problems greatly differing across Europe, and the European Union (EU) faces deep inequalities in MS management from country to country. Through the establishment of a European MS Register (EUReMS), an effective action is proposed to improve the overa...