Björn Tackenberg

• Professor of Neurology MD FEAN FAAN
• Head Integrative Neuroscience at Roche

Objective To investigate the longitudinal dynamics of serum glial fibrillary acidic protein (sGFAP) and serum neurofilament light chain (sNfL) levels in people with multiple sclerosis (pwMS) under B‐cell depleting therapy (BCDT) and their capacity to prognosticate future progression independent of relapse activity (PIRA) events. Methods A total of...

Introduction/Aims Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is characterized by progressive weakness and sensory loss, often affecting patient’s ability to walk and perform activities of daily living independently. Furthermore, patients often report fatigue and depression which can affect their quality of life. These symptoms...

Epstein–Barr virus (EBV) infection precedes multiple sclerosis (MS) pathology and cross-reactive antibodies might link EBV infection to CNS autoimmunity. As an altered anti-EBV T cell reaction was suggested in MS, we queried peripheral blood T cell receptor β chain (TCRβ) repertoires of 1,395 MS patients, 887 controls, and 35 monozygotic, MS-discor...

Autoimmune neurological syndromes (AINS) with autoantibodies against the 65 kDa isoform of the glutamic acid decarboxylase (GAD65) present with limbic encephalitis including temporal lobe seizures or epilepsy, cerebellitis with ataxia, and stiff-person-syndrome, or overlap forms. Anti-GAD65 autoantibodies are also detected in autoimmune diabetes me...

Objective Fatigue is a frequent and severe symptom in multiple sclerosis (MS), but its pathophysiological origin remains incompletely understood. We aimed to examine the predictive value of subcortical gray matter volumes for fatigue severity at disease onset and after four years by applying structural equation modeling (SEM). Methods This multi-c...

It remains largely unclear how thymocytes translate relative differences in T cell receptor (TCR) signal strength into distinct developmental programs that drive the cell fate decisions towards conventional (Tconv) or regulatory T cells (Treg). Following TCR activation, intracellular calcium (Ca ²⁺ ) is the most important second messenger, for whic...

Multiple sclerosis (MS) disease risk is associated with reduced sunexposure. This study assessed the relationship between measures of sun exposure (vitamin D [vitD], latitude) and MS severity in the setting of two multicenter cohort studies (nNationMS = 946, nBIONAT = 990). Additionally, effect-modification by medication and photosensitivityassocia...

Objective In this observational study, we investigated the impact of genetic factors at the immunoglobulin heavy chain constant locus on chromosome 14 and the major histocompatibility complex region on intrathecal immunoglobulin G, A, and M levels as well as on B cells and plasmablasts in the CSF and blood of patients with multiple sclerosis (MS)....

Background: Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) is the first example of a learning health system in multiple sclerosis (MS). This paper describes the initial implementation of MS PATHS and initial patient characteristics. Methods: MS PATHS is an ongoing initiative conducted in 10 healthcare institutions...

Human B cell activating factor (TNFSF13B, BAFF) is a tumor necrosis factor superfamily member. Binding its unique receptor (TNFRSF13C, BAFF-R) mediates gene expression and cell survival in B cells via activation of NFκB pathway. Furthermore, there is data indicating a role in T cell function. A functionally inhibitory isoform (ΔBAFF) resulting from...

Objectives In January 2018, the European Union (EU) approved ocrelizumab in relapsing multiple sclerosis (RMS) and as the first disease-modifying therapy (DMT) for patients with primary progressive multiple sclerosis (PPMS) with efficacy proven in a phase 3 randomised controlled trial. Eleven months prior to the European regulatory approval, a comp...

Background: Multiple sclerosis (MS) disease risk is associated with reduced sun exposure. This study assessed the relationship between measures of sun-exposure (vitamin D (vitD), latitude) and MS disease severity, the mechanisms of action, and effect-modification by medication and sun-sensitivity associated MC1R variants. Methods: Two multi-center...

Objective To assess the impact of APOE polymorphisms on cognitive performance in patients newly diagnosed with clinically isolated syndrome (CIS) or relapsing-remitting MS (RRMS). Methods This multicenter cohort study included 552 untreated patients recently diagnosed with CIS or RRMS according to the 2005 revised McDonald criteria. The single nuc...

Background We aim to evaluate serum neurofilament light chain (sNfL), indicating neuroaxonal damage, as a biomarker at diagnosis in a large cohort of early multiple sclerosis (MS) patients. Methods In a multicentre prospective longitudinal observational cohort, patients with newly diagnosed relapsing-remitting MS (RRMS) or clinically isolated synd...

Objective To determine the prevalence of antibodies to Epstein-Barr virus (EBV) in a large cohort of patients with early multiple sclerosis (MS). Methods Serum samples were collected from 901 patients with a clinically isolated syndrome (CIS) or early relapsing–remitting multiple sclerosis (RRMS) participating in the German National MS cohort, a p...

Background Multiple Sclerosis (MS) is a chronic inflammatory, immune mediated disease of the central nervous system, with Relapsing Remitting MS (RRMS) being the most common type. Within the last years, the status of high disease activity (HDA) has become increasingly important for clinical decisions. Nevertheless, little is known about the inciden...

Pain is frequent in multiple sclerosis (MS) and includes different types, with neuropathic pain (NP) being most closely related to MS pathology. However, prevalence estimates vary largely, and causal relationships between pain and biopsychosocial factors in MS are largely unknown. Longitudinal studies might help to clarify the prevalence and determ...

Background: The risk of progressive multifocal leukoencephalopathy limits the duration over which patients can receive natalizumab before requiring a switch to other therapies such as fingolimod. To date, no studies have assessed the long-term real-world effectiveness and safety of fingolimod following a switch from natalizumab. We aimed to invest...

IL-17-producing CD8+ (Tc17) cells are enriched in active lesions of patients with multiple sclerosis (MS), suggesting a role in the pathogenesis of autoimmunity. Here we show that amelioration of MS by dimethyl fumarate (DMF), a mechanistically elusive drug, associates with suppression of Tc17 cells. DMF treatment results in reduced frequency of Tc...

Nach Jahren niedriger Inzidenz ist in Deutschland seit 2015 eine starke Zunahme gemeldeter Tuberkulose(TB)-Neuerkrankungen zu beobachten. Neue Immuntherapien zur Behandlung der Multiplen Sklerose (MS) gehen mit einer reduzierten Immunkompetenz und einem potenziell erhöhten Infektionsrisiko einher, wobei den meisten behandelnden Neurologen spezifisc...

Introduction: Paraneoplastic autoimmune multi-organ syndrome (PAMS) is a rare clinical condition characterized by variable and heterogeneous clinical phenotypes in the presence of neoplasias which largely depend on the activation of humoral and cellular immune responses. Clinically, these patients present with a spectrum of antibody-driven pemphigu...

Objective To assess the long-term real-world benefit–risk profile of fingolimod in patients with relapsing MS in Germany. Methods This analysis used data from the noninterventional real-world study, Post-Authorization Non-interventional German sAfety study of GilEnyA (PANGAEA), to assess prospectively the persistence, effectiveness, and safety of...

Importance Reliable biomarkers associated with disability worsening in multiple sclerosis (MS) are still needed. Objective To determine a possible association of intrathecal IgG synthesis and early disability worsening as measured by Expanded Disability Status Scale (EDSS) scoring in patients with relapsing-remitting MS or clinically isolated synd...

Background Cognitive impairment (CI) affects approximately one-third of the patients with early multiple sclerosis (MS) and clinically isolated syndrome (CIS). Little is known about factors predicting CI and progression after initial diagnosis. Methods Neuropsychological screening data from baseline and 1-year follow-up of a prospective multicente...

Background Natalizumab (NTZ) was the first approved monoclonal antibody for the treatment of relapsing-remitting multiple sclerosis (RRMS). Despite proven and sustained efficacy, its use is limited by the risk of progressive multifocal leukoencephalopathy (PML). Moreover, some patients show ongoing disease activity under NTZ, requiring a switch to...

Introduction Intravenous immunoglobulin (IVIG) is a potential therapy for chronic inflammatory demyelinating polyneuropathy (CIDP). Methods To investigate the efficacy and safety of the IVIG IgPro10 (Privigen®) for treatment of CIDP, results from PRIMA, a prospective, open‐label, single‐arm study of IVIG in Ig‐naïve or IVIG‐pretreated subjects (NC...

Background and Objectives: To evaluate and validate a subset of candidate biomarkers in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) we prospectively characterized IgG-oligoclonal bands (OCBs), intrathecal IgG antibodies against measles, rubella and varicella zoster viruses (MRZ reaction), CXCL13, neurofilament light chain...

Multiple sclerosis is a complex neurological disease, with ∼20% of risk heritability attributable to common genetic variants, including >230 identified by genome-wide association studies. Multiple strands of evidence suggest that much of the remaining heritability is also due to additive effects of common variants rather than epistasis between thes...

Introduction: Cost of illness studies are needed to estimate societal costs of chronic inflammatory demyelinating polyneuropathy (CIDP) and identify cost-driving factors. Methods: In total, 108 patients were recruited from three specialized neuro-immunological clinics. Costs were calculated for a three-month period including direct and indirect...

The human leukocyte antigen (HLA) haplotype DRB1*15:01 is the major risk factor for multiple sclerosis (MS). Here, we find that DRB1*15:01 is hypomethylated and predominantly expressed in monocytes among carriers of DRB1*15:01. A differentially methylated region (DMR) encompassing HLA-DRB1 exon 2 is particularly affected and displays methylation-se...

Introduction We analysed the efficacy and safety of IVIG IgPro10 (CSL Behring) in two CIDP studies: PRIMA and PATH. Methods PRIMA was a prospective, open-label, single-arm study in 28 CIDP patients (n=13 IVIG-pretreated; n=15 untreated) investigating efficacy and safety of IgPro10 for induction (2 g/kg) and maintenance therapy (1 g/kg every 3 week...

Background Gastrointestinal (GI) events are common adverse events (AEs) associated with delayed-release dimethyl fumarate (DMF), an approved treatment for relapsing–remitting multiple sclerosis (RRMS). The objective of the TOLERATE study was to evaluate GI tolerability and GI mitigation via symptomatic therapies in patients initiating DMF in a real...

Supplement_for_TOLERATE_manuscript – Supplemental material for Incidence and mitigation of gastrointestinal events in patients with relapsing–remitting multiple sclerosis receiving delayed-release dimethyl fumarate: a German phase IV study (TOLERATE)

Multiple sclerosis is a common, complex neurological disease, where almost 20% of risk heritability can be attributed to common genetic variants, including >230 identified by genome-wide association studies (Patsopoulos et al., 2017). Multiple strands of evidence suggest that the majority of the remaining heritability is also due to the additive ef...

Objective: To assess c linical charact eristics, distribution of disease-modifying treatments (DMTs) and neuropsychological symptoms in a large cohort of patients with early-stage multiple sclerosis (MS). Methods: The German National MS cohort is a multi-center prospective longitudinal cohort study that has recruited DMT-naïve patients with clinica...

Background and purpose: The European Charcot Foundation supported development of a set of surveys to understand current practice patterns for diagnosis and management of multiple sclerosis (MS) in Europe. Part 2 of the report summarises survey results related to secondary progressive MS (SPMS), primary progressive MS (PPMS), pregnancy, paediatric...

Background: It is a continuous matter of discussion whether immune activation by vaccination in general and Influenza vaccination in particular increases the risk for clinical deterioration of autoimmune diseases. This prospective study investigated the serological and clinical course of autoimmune Myasthenia gravis (MG) after a seasonal influenza...

The population with multiple sclerosis receiving treatment in clinical practice differs from that in randomized controlled trials (RCTs). An assessment of the real-world benefit-risk profile of therapies is needed. This analysis used data from the large, noninterventional, observational German study Post-Authorization Non-interventional German sAfe...

Autoreactive antibodies against the proteins alpha-synuclein (α-syn) and tau are detectable in body fluids of both healthy and diseased elderly people. However, nothing is known about their presence or titers in children. To close this gap and to characterize their temporary expression levels, we used ELISA techniques to investigate the serum titer...

There is a need for diagnostic biomarkers of epilepsy and status epilepticus to support clinical examination, electroencephalography and neuroimaging. Extracellular microRNAs may be potentially ideal biomarkers since some are expressed uniquely within specific brain regions and cell types. Cerebrospinal fluid offers a source of microRNA biomarkers...

Die Myasthenia gravis ist eine Autoimmunerkrankung, die zu einer belastungsabhängigen Muskelschwäche der Willkürmotorik mit Erholung in Ruhe führt. Ursache sind Autoantikörper gegen den postsynaptischen nikotinergen Acetylcholinrezeptor (AChR) und gegen andere Komponenten der neuromuskulären Übertragung. Nerven und Muskeln sind dabei intakt. Erkran...

Background The effect of dimethyl fumarate (DMF) on circulating lymphocyte subsets and their contribution as predictors of clinical efficacy have not yet been investigated in multiple sclerosis (MS). Objective To evaluate lymphocytes and lymphocyte subsets (analyzed 6 months after DMF start) in MS patients with and without disease activity after 1...

Background and purpose: Up-to-date information is needed on the extent to which neurologists treating multiple sclerosis (MS) in Europe are integrating rapidly evolving diagnostic criteria, disease-modifying therapies and recommendations for monitoring disease activity into their clinical practice. Methods: A steering committee of MS neurologist...

Background The PMP22 gene encodes a protein integral to peripheral myelin. Its deletion leads to hereditary neuropathy with liability to pressure palsies (HNPP). PMP22 is not expressed in the adult central nervous system, but previous studies suggest a role in CNS myelin development. The objective of this study was to identify potential structural...

Myasthenia gravis (MG) is an autoimmune antibody-mediated disorder of neuromuscular synaptic transmission. The clinical hallmark of MG consists of fluctuating fatigability and weakness affecting ocular, bulbar and (proximal) limb skeletal muscle groups. MG may either occur as an autoimmune disease with distinct immunogenetic characteristics or as a...

Background Natalizumab provides rapid and high-efficacy control of multiple sclerosis disease activity with long-term stabilization. However, the benefits of the drug are countered by a risk of developing progressive multifocal leukoencephalopathy in patients infected with the John Cunningham Virus. Close monitoring is required in patients with inc...

Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common chronic autoimmune neuropathy. While both cell-mediated and humoral mechanisms contribute to its pathogenesis, the rapid clinical response to plasmapheresis implicates a circulating factor responsible for peripheral nerve injury. We report that treatment-naïve patients with...

We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to...

Myasthenia gravis is an autoimmune disease, which leads to load-dependent weakness of voluntary skeletal muscles with recovery of function after resting. The disease is caused by autoantibodies directed against the postsynaptic nicotinic acetylcholine receptors (AChR) leading to a reduction of neuromuscular transmission. Muscles and nerves are not...