Tjalf Ziemssen

• MD
• Consultant at TU Dresden

Walking impairments represent one of the most debilitating symptom areas for people with multiple sclerosis (MS). It is important to detect even slightest walking impairments in order to start and optimize necessary interventions in time to counteract further progression of the disability. For this reason, a regular monitoring through gait analysis...

An individualized innovative disease management is of great importance for people with multiple sclerosis (pwMS) to cope with the complexity of this chronic, multidimensional disease. However, an individual state of the art strategy, with precise adjustment to the patient’s characteristics, is still far from being part of the everyday care of pwMS....

Multiple sclerosis (MS) is the most common chronic autoimmune neurological disease. Its therapeutic management has drastically evolved in the recent years with the development of specific disease-modifying therapies (DMTs). Together with the established injectables, oral and intravenous alternatives are now available for MS patients with significan...

Absolute (molar) quantification of proteins provides the analytical rationale for system-level modelling of diverse molecular mechanisms. FastCAT method employs multiple short (<50 kDa) stable-isotope labeled chimeric proteins (CPs) composed of concatenated quantotypic (Q-) peptides representing the quantified proteins. Each CP also comprises scram...

The development of digital applications and remote communication technologies for people with multiple sclerosis (pwMS) has increased rapidly in recent years. eHealth apps have been shown to improve outcomes and facilitate access to care, disease information, and support. On the patient side, pwMS facing a disease onset in their early adulthood are...

To ensure goal-directed behavior in daily life, the use of inhibitory control is of great importance. The aim of this study is to shed light on the underlying neuronal mechanisms of inhibitory control and the relevance of cytoarchitectonic integrity in it. We combine sophisticated EEG analysis techniques assessing directed communication between bra...

Background/Objectives: The COVID-19 pandemic disrupted healthcare systems globally, altering the management of chronic conditions like multiple sclerosis (MS) and interrupting the regular monitoring and support that people with MS (pwMS) typically need. The aim of this study was to examine changes in the utilization of MS healthcare resources over...

Disease-modifying therapies (DMTs) are known to impact cellular and humoral immune response in persons with multiple sclerosis (pwMS). In this study, we performed in-depth SARS-CoV-2-specific T-cell profiling using flow cytometry. T-cell immunity in pwMS with or without DMTs was evaluated before a first SARS-CoV-2 messenger ribonucleic acid (mRNA)...

Background Alemtuzumab is a disease-modifying therapy for highly active relapsing-remitting multiple sclerosis (RRMS). Sustained efficacy up to 9 years was observed in the phase IIIb/IV open-label TOPAZ clinical trial and assessed in the real-world retrospective and prospective study, TREAT-MS. Objectives To examine long-term efficacy and safety o...

Background and objectives: Patients with multiple sclerosis (MS) may demonstrate better disease control when treatment is initiated on high-efficacy disease-modifying therapies (DMTs) from onset. This subgroup analysis assessed the long-term efficacy and safety profile of the high-efficacy DMT ocrelizumab (OCR) as first-line therapy for early-stag...

Precision medicine involves a paradigm shift toward personalized data-driven clinical decisions. The concept of a medical “digital twin” has recently become popular to designate digital representations of patients as a support for a wide range of data science applications. However, the concept is ambiguous when it comes to practical implementations...

Background Natalizumab (NAT) is an established disease-modifying therapy (DMT) for highly active multiple sclerosis (MS). However, its use involves complex decision-making, often leading to initial use of lower efficacy therapies. Recently, the first biosimilar NAT was approved, enabling competitive pricing. This study assessed the societal implica...

Background The aim of this study was to investigate the dynamics of annual whole brain volume loss (BVL/year) and annual thalamic volume loss (ThalaVL/year) in patients with relapsing-remitting multiple sclerosis (PwRRMS) during the course of the disease. Methods A longitudinal database of magnetic resonance imaging (MRI) scans of 195 healthy indi...

Background The quality of treatment is especially critical in the context of complex and chronic diseases such as multiple sclerosis (MS). The Brain Health Initiative, an independent international consortium of neurologists, reached a consensus on time-based quality standards prioritizing brain health-focused care for people with MS. Objectives To...

Background Best supportive care (BSC) measures are an essential component for the management of primary progressive multiple sclerosis (PPMS). Objectives RETRO PPMS (ML39631) is the first study to systematically analyze the therapeutic journey and standard of BSC of patients with PPMS in Germany. Design This multicenter, non-interventional study...

Purpose Understanding the long-term safety of disease-modifying therapies for multiple sclerosis (MS) in routine clinical practice can be undertaken through registry-based studies. However, variability of data quality across such sources poses the challenge of data fit for regulatory decision-making. CLARION, a non-interventional cohort safety stud...

Background and objectives: Attack prevention is crucial in managing neuromyelitis optica spectrum disorders (NMOSDs). Eculizumab (ECU), an inhibitor of the terminal complement cascade, was highly effective in preventing attacks in a phase III trial of aquaporin-4 (AQP4)-IgG seropositive(+) NMOSDs. In this article, we evaluated effectiveness and sa...

Importance New anti-tumor treatments, such as immune checkpoint inhibitors and CAR T-cell therapy, are associated with an increasing number of neurological issues linked to tumors not arising from nervous system such as neurological and neuropsychological side effects that can significantly impair quality of life in the short or long term. The scie...

Use of techniques derived from generative artificial intelligence (AI), specifically large language models (LLMs), offer a transformative potential on the management of multiple sclerosis (MS). Recent LLMs have exhibited remarkable skills in producing and understanding human-like texts. The integration of AI in imaging applications and the deployme...

Background Siponimod, a second-generation, selective sphingosine 1-phosphate receptor (S1PR) 1 and 5 modulator, represents an important therapeutic choice for active secondary progressive multiple sclerosis (SPMS). Besides the beneficial immunomodulatory effects, siponimod impacts cardiovascular function through S1PR1 modulation. Short-term vagomim...

Multiple sclerosis (MS) is a chronic neuroinflammatory disease characterized by central nervous system demyelination and axonal degeneration. Fatigue affects a major portion of MS patients, significantly impairing their daily activities and quality of life. Despite its prevalence, the mechanisms underlying fatigue in MS are poorly understood, and m...

The use of extracorporeal membrane oxygenation (ECMO) has grown rapidly, driven by the COVID-19 pandemic. Despite its widespread adoption, neurological complications pose a significant risk, impacting both mortality and survivors’ quality of life. Detecting these complications is challenging due to sedation and the heterogeneous nature of ECMO-asso...

In recent years, Raman spectroscopy has garnered growing interest in the field of biomedical research. It offers a non-invasive and label-free approach to defining the molecular fingerprint of immune cells. We utilized Raman spectroscopy on optically trapped immune cells to investigate their molecular compositions. While numerous immune cell types...

Deep brain stimulation (DBS) is an efficient treatment for movement disorders, most commonly Parkinson’s Disease (PD), dystonia and essential tremor. DBS surgery carries risks, e.g. the risk of delayed peri-lead edema (PLE) and the risk of postoperative cognitive decline. The mechanisms of these complications are not fully understood and there is n...

Multiple sclerosis (MS) is a devastating immune-mediated disorder of the central nervous system resulting in progressive disability accumulation. As there is no cure available yet for MS, the primary therapeutic objective is to reduce relapses and to slow down disability progression as early as possible during the disease to maintain and/or improve...

Aim Diroximel fumarate (DRF), ozanimod (OZA) and interferon beta-1a (IFN) are disease-modifying therapies approved for the treatment of relapsing multiple sclerosis. No randomized trials have compared DRF versus OZA and IFN. We compared DRF versus OZA and DRF versus IFN using matching-adjusted indirect comparisons for efficacy outcomes, including a...

Objectives To evaluate the prognostic value of 3- and 12-month on-treatment serum neurofilament light chain (sNfL) levels for future disease activity in with relapsing multiple sclerosis[pwRMS] Methods A baseline sNfL cut-off was predefined by the median sNfL value across the ofatumumab ASCLEPIOS I/II Phase 3 clinical trials and participants were...

The authors would like to make the following corrections to this published paper [...]

During the COVID-19 pandemic, people with multiple sclerosis (MS) and their healthcare providers have faced unique challenges related to the interaction between SARS-CoV-2, underlying neurological disease and the use of disease-modifying treatments (DMTs). Key concerns arose, primarily related to the possibility that SARS-CoV-2 infection could trig...

Machine learning (ML) has emerged as a powerful tool in multiple sclerosis (MS) research, enabling more accurate diagnosis, prognosis prediction, and treatment optimization. However, the complexity of developing and deploying ML models poses challenges for domain experts without extensive programming knowledge. We propose a novel domain-specific la...

In EVOLVE-MS-1 (NCT02634307), mean absolute lymphocyte count (ALC) on diroximel fumarate (DRF) declined from baseline by approximately 28% in year 1, then stabilized, similar to ALC decline observed with dimethyl fumarate (DMF). Prior studies reported that clinical efficacy of DMF was not substantially different in patients with and without lymphop...

Disease-modifying therapies (DMTs) impact the cellular immune response to severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccines in patients with multiple sclerosis (pwMS). In this study, we aim to elucidate the characteristics of the involved antigen-specific T cells via the measurement of broad cytokine profiles in pwMS on var...

Background The primary treatment for acute relapses in multiple sclerosis (MS) is the intravenous administration of high-dose methylprednisolone (IVMP). However, the mechanisms through which corticosteroid treatment impacts acute neuroinflammation in people with MS (pwMS) remain not fully understood. In particular, the changes induced by glucocorti...

Background In patients with relapsing remitting multiple sclerosis (RRMS) on low‐efficacy disease modifying therapies (DMT), the optimal strategy on how to escalate treatment once needed, remains unknown. Methods We studied RRMS patients on low‐efficacy DMTs listed in the Swiss National Treatment Registry, who underwent escalation to either medium...

(1) Background: The countermovement jump (CMJ) on a force plate could be a sensitive assessment for detecting early lower-limb muscle mechanical deficits in the early stages of multiple sclerosis (MS). CMJ performance is known to be influenced by various anthropometric, physiological, and biomechanical factors, mostly investigated in children and a...

Aim: To assess time to improvement in Quality of Life in Neurological Disorders (Neuro-QoL) domains for patients treated with natalizumab versus ocrelizumab. Methods: Patients enrolled in the MS PATHS network who initiated treatment with either natalizumab or ocrelizumab rated the Neuro-QoL domains of physical function, symptoms, emotional health,...

Background In the early stages of multiple sclerosis (MS), there are no objective sensitive functional assessments to identify and quantify early subclinical neuromuscular deficits and lower limb strength asymmetries during complex movements. Single-countermovement jumps (SLCMJ), a maximum single leg vertical jump, on a force plate allow functional...

Neurofilament proteins have been validated as specific body fluid biomarkers of neuro-axonal injury. The advent of highly sensitive analytical platforms that enable reliable quantification of neurofilaments in blood samples and simplify longitudinal follow-up has paved the way for the development of neurofilaments as a biomarker in clinical practic...

Background: With a rising number of multiple sclerosis (MS) cases and increasing pressure on health systems, digital companion apps like Brisa, designed specifically for people with MS, can play an important role in the patient journey. These apps enable the collection of real-time longitudinal data that are critical to our understanding of the pat...

Multiple sclerosis (MS) as a chronic, degenerative autoimmune disease of the central nervous system has a longitudinal and heterogeneous course with increasing treatment options and risk profiles requiring constant monitoring of a growing number of parameters. Despite treatment guidelines, there is a lack of strategic and individualised monitoring...

Background While evidence highlights the effectiveness of initiating disease-modifying therapy with a high-efficacy medication for multiple sclerosis (MS) patients with poor prognostic factors, it remains unclear whether this approach has been adopted by a broad range of MS providers in Germany yet. Objective To assess the adoption of the early hi...

The retina has been considered a "window to the brain" and shares similar innervation by the dopaminergic system with the cortex in terms of an unequal distribution of D1 and D2 receptors. Here, we provide a comprehensive overview that Optical Coherence Tomography (OCT), a non-invasive imaging technique, which provides an "in vivo" representation o...

Importance Biomarkers distinguishing nonrelapsing progressive disease biology from relapsing biology in multiple sclerosis (MS) are lacking. Cerebrospinal fluid (CSF) is an accessible fluid that most closely reflects central nervous system biology. Objective To identify CSF biological measures associated with progressive MS pathobiology. Design,...

A fundamental challenge for personalized medicine is to capture enough of the complexity of an individual patient to determine an optimal way to keep them healthy or restore their health. This will require personalized computational models of sufficient resolution and with enough mechanistic information to provide actionable information to the clin...

The SARS-CoV-2 pandemic profoundly impacted people with multiple sclerosis (pwMS). Disease-related aspects and demographic factors may influence vaccination rates, infection susceptibility, and severity. Despite prior research, comprehensive real-world data obtained throughout the pandemic remain limited. We investigated SARS-CoV-2 vaccination and...

Background To reduce the risk of long-term disability in people with Multiple Sclerosis (pwMS), an increasing number of disease-modifying immune therapies (DMT) are available, involving diverse mechanisms of action, levels of efficacy, treatment risks, and tolerability aspects. Including patient preferences and expectations in shared decision-makin...

Medical digital twins are computational models of human biology relevant to a given medical condition, which are tailored to an individual patient, thereby predicting the course of disease and individualized treatments, an important goal of personalized medicine. The immune system, which has a central role in many diseases, is highly heterogeneous...

Recent advances in the field of artificial intelligence (AI) could yield new insights into the potential causes of multiple sclerosis (MS) and factors influencing its course as the use of AI opens new possibilities regarding the interpretation and use of big data from not only a cross-sectional, but also a longitudinal perspective. For each patient...

Our everyday activities require the maintenance and continuous updating of information in working memory (WM). To control this dynamic, WM gating mechanisms have been suggested to be in place, but the neurophysiological mechanisms behind these processes are far from being understood. This is especially the case when it comes to the role of oscillat...

Obstructive sleep apnea is associated with cognitive impairment and increased risk for neurodegenerative diseases. Obstructive sleep apnea treatment with positive airway pressure therapy helps to improve cognitive symptoms and reduces long-term dementia risk. To test whether these treatment effects are due to a reduction in neuronal damage, we exam...

Multiple sclerosis (MS) is a disabling disease with unpredictable clinical manifestations. As clinical assessments may not fully capture the impact of MS on quality of life, they can be complemented by patient-reported outcome (PRO) measures to provide a more comprehensive picture of MS disease state and impact. The objectives of this study were to...

Booster vaccinations against SARS-CoV-2 are recommended 6–12 months after the last dose or infection in elderly and high-risk groups. The present analysis aims to evaluate whether an interval shorter than 12 months is required in multiple sclerosis patients receiving ofatumumab. Neutralizing antibody status over 1 year in patients receiving booster...

Objective This study aims at understanding the impact of ofatumumab treatment on the development of cellular and humoral immune responses to initial and booster SARS-CoV-2 mRNA vaccines. Methods KYRIOS is an open-label, prospective, two-cohort study at eight sites in Germany including 40 MS patients who receive SARS-CoV-2 mRNA vaccination either b...

Objective To understand the longitudinal cellular and humoral immune responses to SARS-CoV-2 mRNA vaccines depending on the timing of vaccination and siponimod treatment. Methods AMA-VACC is an open-label, three-cohort, prospective study in Germany with 41 multiple sclerosis patients currently treated with siponimod, any first-line DMT or without...

The landscape of immunotherapies in the management of Multiple Sclerosis (MS) is currently particularly dynamic. Over 21 immunotherapeutic options are approved by the European Meidcines Agency (EMA), Food and Drug Administration (FDA) and newer approaches are ongoing in clinical trials. With advancements in the understanding of MS pathophysiology a...

Objective Repeated intravenous administration of anti‐CD20 depleting monoclonal antibodies 6 months apart is among the highly effective treatment options in multiple sclerosis (MS). Here, we aimed to investigate peripheral immune cell subset depletion kinetics following either rituximab (RTX) or ocrelizumab (OCR) infusions in people with MS (pwMS)....

Different stages of Parkinson’s disease (PD) are defined by clinical criteria, while late-stage PD is marked by the onset of morbidity milestones and rapid clinical deterioration. Based on neuropathological evidence, degeneration in the dopaminergic system occurs primarily in the early stage of PD, raising the question of what drives disease progre...

Background The aim of this study was to examine the societal costs of polypharmacy in patients with multiple sclerosis (MS). We therefore focused on the association between the number of medications on the level of care (LOC), the German classification of the need for care, and the number of therapy sessions (TTU). Methods In addition to demograph...

Einleitung: Eine Vielzahl von Studien zeigt, dass eine einseitige leichte Parese der unteren Extremität (UEX) Einfluss auf Gehfähigkeit, Gleichgewicht und Alltagsfunktionen bei Multiple Sklerose (MS) hat [1]. Im Frühstadium der MS gibt es, neben manuellen Muskelfunktionstest (mMFT) und Dynamometermessungen, derzeit keine empfindlichen funktione...

Einleitung: Die Fußheberschwäche ist ein häufiges Symptom verschiedener neurologischer Erkrankungen wie z. B. Multiple Sklerose, Schlaganfall oder Zerebralparese. Sie beeinflusst die Gangstabilität und erhöht das Sturzrisiko, was zu ernsthaften Folgen führen kann. Als symptomatische Behandlung der Fußheberschwäche wird für Personen mit Multipler Sk...

Background The Expanded Disability Status Scale (EDSS) quantifies disability and measures disease progression in multiple sclerosis (MS), however is not available in administrative claims databases. Objectives To develop a claims-based algorithm for deriving EDSS and validate it against a clinical dataset capturing true EDSS values from medical re...

Prof. Dr Tjalf Ziemssen sees himself as a digital pioneer with a lot of passion. Alongside and parallel to his day-to-day work at the Centre for Clinical Neurosciences at the Neurological University Hospital Dresden, treating patients with multiple sclerosis, he and his team are developing the concept of the ‚digital MS twin‘. This can be thought o...

Einleitung: Multiple Sklerose (MS) ist die häufigste chronisch-entzündliche Erkrankung des zentralen Nervensystems, die regelhaft mit Gang- und Gleichgewichtsstörungen bei Personen mit MS (PmMS) einhergeht. Die Gangstörung bei MS wird durch diverse pathophysiologische Faktoren wie z.B. Spastik, Paresen oder Sensibilitäts- und Koordinationsstörungen...

Hintergrund: Multiple Sklerose (MS) ist eine chronisch entzündliche Erkrankung des ZNS, die mit vielfältigen Defi ziten, wie pathologischer Ermüdbarkeit bei Belastung, einhergeht. Trotz hoher Symptomprävalenz gibt es nur wenige Methoden, diese zu objektivieren. Zur Identifizierung von Änderungen der Bewegungsmuster bei PmMS mit Ermüdbarkeit werden...

Background Diroximel fumarate (DRF) is approved for adults with relapsing–remitting multiple sclerosis (RRMS) in Europe and for relapsing forms of MS in the United States. DRF and dimethyl fumarate (DMF) yield bioequivalent exposure of the active metabolite monomethyl fumarate. Prior studies indicated fewer gastrointestinal (GI)-related adverse eve...