Publications by authors named "Heinz Wiendl"

469 Publications

[Multiple sclerosis treatment consensus group (MSTCG): position paper on disease-modifying treatment of multiple sclerosis 2021 (white paper)].

Nervenarzt 2021 Jul 23. Epub 2021 Jul 23.

Multiple Sklerose Therapie Konsensus Gruppe (MSTKG), Münster, Deutschland.

Multiple sclerosis is a complex, autoimmune-mediated disease of the central nervous system characterized by inflammatory demyelination and axonal/neuronal damage. The approval of various disease-modifying therapies and our increased understanding of disease mechanisms and evolution in recent years have significantly changed the prognosis and course of the disease. This update of the Multiple Sclerosis Therapy Consensus Group treatment recommendation focuses on the most important recommendations for disease-modifying therapies of multiple sclerosis in 2021. Our recommendations are based on current scientific evidence and apply to those medications approved in wide parts of Europe, particularly German-speaking countries (Germany, Austria, Switzerland).
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http://dx.doi.org/10.1007/s00115-021-01157-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300076PMC
July 2021

Determinants of cognition in autoimmune limbic encephalitis-A retrospective cohort study.

Hippocampus 2021 Jul 16. Epub 2021 Jul 16.

Department of Neurology with Institute of Translational Neurology, Westfälische Wilhelms-University of Münster, Münster, Germany.

Autoimmune limbic encephalitis (ALE) is the most common type of autoimmune encephalitis (AIE). Subacute memory disturbance, temporal lobe seizures, and psychiatric symptoms are clinical hallmarks of the disease. However, little is known on the factors contributing to cognitive functioning in ALE. Hence, we here investigate major determinants of cognitive functioning in ALE. In a retrospective analysis of 102 patients with ALE, we first compared verbal learning capacity, nonverbal learning capacity, and attentional and executive functioning by absence or presence of different types of neural autoantibodies (AABs). Subsequently we established three linear regression models including 63, 38, and 61 patients, respectively to investigate how cognitive functioning in these domains may depend on common markers of ALE such as intrathecal inflammation, blood-cerebrospinal fluid (CSF)-barrier function, mesiotemporal epileptiform discharges and slowing, determined by electroencephalography (EEG) and structural mesiotemporal changes, measured with magnetic resonance imaging (MRI). We also accounted for possible effects of cancer- and immunotherapy and other centrally effective medication. There was no effect of AAB status on cognitive functioning. Although the regression models could not predict verbal and nonverbal learning capacity, structural mesiotemporal neural network alterations on T2-/fluid attenuated inversion recovery (FLAIR)-signal-weighted MRI and mesiotemporal epileptiform discharges or slowing on EEG exerted a significant impact on memory functions. In contrast, the regression model significantly predicted attentional and executive functioning with CSF white blood cell count and centrally effective medication being significant determinants. In this cohort, cognitive functioning in ALE does not depend on the AAB status. Common markers of ALE cannot predict memory functioning that only partially depends on structural and functional alterations of mesiotemporal neural networks. Common markers of ALE significantly predict attentional and executive functioning that is significantly related to centrally effective medication and CSF white blood cell count, which may point toward inflammation affecting brain regions beyond the limbic system.
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http://dx.doi.org/10.1002/hipo.23375DOI Listing
July 2021

Ocrelizumab Extended Interval Dosing in Multiple Sclerosis in Times of COVID-19.

Neurol Neuroimmunol Neuroinflamm 2021 09 14;8(5). Epub 2021 Jul 14.

From the Department of Neurology with Institute of Translational Neurology (L.R., M.P., S.P., C.N., L.K., H.W.), University Hospital Muenster, Germany; Institute for Biometrics and Bioinformatic (A.L.), Otto-von-Guericke University, Magdeburg, Germany; Department for Neurology (R.P., C.K., K.K., R.R.), University Hospital Essen, Germany; Focus Program Translational Neurosciences (FTN) and Immunology (FZI) (K.P., S.B., F.Z.), Rhine Main Neuroscience Network (rmn2), Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Germany; Department of Neurology (C.W., Y.G., M.S.), University Hospital Cologne, Germany; and Department of Neurology (J.I., O.A., T.R., S.G.M.), Heinrich-Heine University, Duesseldorf, Germany.

Objective: To evaluate the clinical consequences of extended interval dosing (EID) of ocrelizumab in relapsing-remitting multiple sclerosis (RRMS) during the coronavirus disease 2019 (COVID-19) pandemic.

Methods: In our retrospective, multicenter cohort study, we compared patients with RRMS on EID (defined as ≥4-week delay of dose interval) with a control group on standard interval dosing (SID) at the same period (January to December 2020).

Results: Three hundred eighteen patients with RRMS were longitudinally evaluated in 5 German centers. One hundred sixteen patients received ocrelizumab on EID (median delay [interquartile range 8.68 [5.09-13.07] weeks). Three months after the last ocrelizumab infusion, 182 (90.1%) patients following SID and 105 (90.5%) EID patients remained relapse free ( 0.903). Three-month confirmed progression of disability was observed in 18 SID patients (8.9%) and 11 EID patients (9.5%, = 0.433). MRI progression was documented in 9 SID patients (4.5%) and 8 EID patients (6.9%) at 3-month follow-up ( = 0.232). Multivariate logistic regression showed no association between treatment regimen and no evidence of disease activity status at follow-up (OR: 1.266 [95% CI: 0.695-2.305]; 0.441). Clinical stability was accompanied by persistent peripheral CD19 B-cell depletion in both groups (SID vs EID: 82.6% vs 83.3%, 0.463). Disease activity in our cohort was not associated with CD19 B-cell repopulation.

Conclusion: Our data support EID of ocrelizumab as potential risk mitigation strategy in times of the COVID-19 pandemic.

Classification Of Evidence: This study provides Class IV evidence that for patients with RRMS, an EID of at least 4 weeks does not diminish effectiveness of ocrelizumab.
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http://dx.doi.org/10.1212/NXI.0000000000001035DOI Listing
September 2021

Single-cell profiling of CNS border compartment leukocytes reveals that B cells and their progenitors reside in non-diseased meninges.

Nat Neurosci 2021 Jul 12. Epub 2021 Jul 12.

Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Medical Faculty, Münster, Germany.

The CNS is ensheathed by the meninges and cerebrospinal fluid, and recent findings suggest that these CNS-associated border tissues have complex immunological functions. Unlike myeloid lineage cells, lymphocytes in border compartments have yet to be thoroughly characterized. Based on single-cell transcriptomics, we here identified a highly location-specific composition and expression profile of tissue-resident leukocytes in CNS parenchyma, pia-enriched subdural meninges, dura mater, choroid plexus and cerebrospinal fluid. The dura layer of the meninges contained a large population of B cells under homeostatic conditions in mice and rats. Murine dura B cells exhibited slow turnover and long-term tissue residency, and they matured in experimental neuroinflammation. The dura also contained B lineage progenitors at the pro-B cell stage typically not found outside of bone marrow, without direct influx from the periphery or the skull bone marrow. This identified the dura as an unexpected site of B cell residence and potentially of development in both homeostasis and neuroinflammation.
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http://dx.doi.org/10.1038/s41593-021-00880-yDOI Listing
July 2021

Diagnostic utility of cerebrospinal fluid (CSF) findings in seizures and epilepsy with and without autoimmune-associated disease.

Seizure 2021 Jun 29;91:233-243. Epub 2021 Jun 29.

Department of Neurology with Institute of Translational Neurology, University of Münster, Albert-Schweitzer-Campus 1, Gebäude A1, 48149 Münster, Germany. Electronic address:

Patients with seizures and epilepsy routinely undergo multiple diagnostic tests, which may include cerebrospinal fluid (CSF) analysis. This review aims to outline different CSF parameters and their alterations in seizures or epilepsy. We then discuss the utility of CSF analysis in seizure patients in different clinical settings in depth. Some routine CSF parameters are frequently altered after seizures, but are not specific such as CSF protein and lactate. Pleocytosis and CSF specific oligoclonal bands are rare and should be considered as signs of infectious or immune mediated seizures and epilepsy. Markers of neuronal damage show conflicting results, and are as yet not established in clinical practice. Parameters of neuronal degeneration and more specific immune parameters are less well studied, and are areas of further research. CSF analysis in new-onset seizures or status epilepticus serves well in the differential diagnosis of seizure etiology. Here, considerations should include autoimmune-associated seizures. CSF findings in these disorders are a special focus of this review and are summarized in a comprehensive overview. Until now, CSF analysis has not yielded clinically helpful biomarkers for refractory epilepsy or for assessment of neuronal damage which is a subject of further studies.
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http://dx.doi.org/10.1016/j.seizure.2021.06.030DOI Listing
June 2021

Confirmed 6-Month Disability Improvement and Worsening Correlate with Long-term Disability Outcomes in Alemtuzumab-Treated Patients with Multiple Sclerosis: Post Hoc Analysis of the CARE-MS Studies.

Neurol Ther 2021 Jun 24. Epub 2021 Jun 24.

Univ. Lille, INSERM U1172 LilNCog, CHU Lille, FHU Precise, Lille, France.

Introduction: In the 2-year CARE-MS trials (NCT00530348; NCT00548405) in patients with relapsing-remitting multiple sclerosis, alemtuzumab showed superior efficacy versus subcutaneous interferon beta-1a. Efficacy was maintained in two consecutive extensions (NCT00930553; NCT02255656). This post hoc analysis compared disability outcomes over 9 years among alemtuzumab-treated patients according to whether they experienced confirmed disability improvement (CDI) or worsening (CDW) or neither CDI nor CDW.

Methods: CARE-MS patients were randomized to receive two alemtuzumab courses (12 mg/day; 5 days at baseline; 3 days at 12 months), with additional as-needed 3-day courses in the extensions. CDI or CDW were defined as ≥ 1.0-point decrease or increase, respectively, in Expanded Disability Status Scale (EDSS) score from core study baseline confirmed over 6 months, assessed in patients with baseline EDSS score ≥ 2.0. Improved or stable EDSS scores were defined as ≥ 1-point decrease or ≤ 0.5-point change (either direction), respectively, from core study baseline. Functional systems (FS) scores were also assessed.

Results: Of 511 eligible patients, 43% experienced CDI and 34% experienced CDW at any time through year 9 (patients experiencing both CDI and CDW were counted in each individual group); 29% experienced neither CDI nor CDW. At year 9, patients with CDI had a -0.58-point mean EDSS score change from baseline; 88% had stable or improved EDSS scores. Improvements occurred across all FS, primarily in sensory, pyramidal, and cerebellar domains. Patients with CDW had a +1.71-point mean EDSS score change; 16% had stable or improved EDSS scores. Patients with neither CDI nor CDW had a -0.10-point mean EDSS score change; 98% had stable or improved EDSS scores.

Conclusion: CDI achievement at any point during the CARE-MS studies was associated with improved disability at year 9, highlighting the potential of alemtuzumab to change the multiple sclerosis course. Conversely, CDW at any point was associated with worsened disability at year 9.
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http://dx.doi.org/10.1007/s40120-021-00262-3DOI Listing
June 2021

Failed, Interrupted, or Inconclusive Trials on Neuroprotective and Neuroregenerative Treatment Strategies in Multiple Sclerosis: Update 2015-2020.

Drugs 2021 Jun 4;81(9):1031-1063. Epub 2021 Jun 4.

Department of Neurology, Medical Faculty, Heinrich Heine University Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany.

In the recent past, a plethora of drugs have been approved for the treatment of multiple sclerosis (MS). These therapeutics are mainly confined to immunomodulatory or immunosuppressive strategies but do not sufficiently address remyelination and neuroprotection. However, several neuroregenerative agents have shown potential in pre-clinical research and entered Phase I to III clinical trials. Although none of these compounds have yet proceeded to approval, understanding the causes of failure can broaden our knowledge about neuroprotection and neuroregeneration in MS. Moreover, most of the investigated approaches are characterised by consistent mechanisms of action and proved convincing efficacy in animal studies. Therefore, learning from their failure will help us to enforce the translation of findings acquired in pre-clinical studies into clinical application. Here, we summarise trials on MS treatment published since 2015 that have either failed or were interrupted due to a lack of efficacy, adverse events, or for other reasons. We further outline the rationale underlying these drugs and analyse the background of failure to gather new insights into MS pathophysiology and optimise future study designs. For conciseness, this review focuses on agents promoting remyelination and medications with primarily neuroprotective properties or unconventional approaches. Failed clinical trials that pursue immunomodulation are presented in a separate article.
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http://dx.doi.org/10.1007/s40265-021-01526-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217012PMC
June 2021

Fc-Receptor Targeted Therapies for the Treatment of .

Int J Mol Sci 2021 May 28;22(11). Epub 2021 May 28.

Department of Neurology with Institute of Translational Neurology, University Hospital Münster, 48149 Münster, Germany.

(MG) is an autoimmune disease in which immunoglobulin G (IgG) antibodies (Abs) bind to acetylcholine receptors (AChR) or to functionally related molecules in the postsynaptic membrane at the neuromuscular junction. IgG crystallizable fragment (Fc)-mediated effector functions, such as antibody-dependent complement deposition, contribute to disease development and progression. Despite progress in understanding Ab-mediated disease mechanisms, immunotherapy of MG remained rather unspecific with corticosteroids and maintenance with immunosuppressants as first choice drugs for most patients. More specific therapeutic IgG Fc-based platforms that reduce serum half-life or effector functions of pathogenic MG-related Abs are currently being developed, tested in clinical trials or have recently been successfully translated into the clinic. In this review, we illustrate mechanisms of action and clinical efficacies of emerging Fc-mediated therapeutics such as neonatal Fc receptor (FcRn)-targeting agents. Furthermore, we evaluate prospects of therapies targeting classical Fc receptors that have shown promising therapeutic efficacy in other antibody-mediated conditions. Increased availability of Fc- and Fc receptor-targeting biologics might foster the development of personalized immunotherapies with the potential to induce sustained disease remission in patients with MG.
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http://dx.doi.org/10.3390/ijms22115755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198115PMC
May 2021

Profiling Complement System Components in Primary CNS Vasculitis.

Cells 2021 May 8;10(5). Epub 2021 May 8.

Department of Neurology with Institute of Translational Neurology, University Hospital Münster, 48149 Münster, Germany.

Complement activation has been implicated in the pathogenesis of many vasculitic syndromes such as anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides. Using an array-based multiplex system, we simultaneously quantified serum and CSF levels of activated and regulatory complement system proteins in patients with primary CNS vasculitis (PACNS; = 20) compared to patients with non-inflammatory conditions ( = 16). Compared to non-inflammatory controls, levels of C3a, C5a, and SC5b-9, indicative for general activation of the complement system, of C4a, specific for the activation of the classical pathway, Ba and Bb, reflective for alternative complement activation as well as concentrations of complement-inhibitory proteins factor H and factor I were unchanged in patients with PACNS. Our study does not support the hypothesis that complement activation is systemically increased in patients with PACNS.
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http://dx.doi.org/10.3390/cells10051139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150982PMC
May 2021

Intrathecal Immunoglobulin M Synthesis is an Independent Biomarker for Higher Disease Activity and Severity in Multiple Sclerosis.

Ann Neurol 2021 May 31. Epub 2021 May 31.

Neurology Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.

Objective: We aimed to determine in relapsing multiple sclerosis (MS) whether intrathecal synthesis of immunoglobulin (Ig) M and IgG is associated with outcomes reflecting inflammatory activity and chronic worsening.

Methods: We compared cerebrospinal fluid analysis, clinical and magnetic resonance imaging data, and serum neurofilament light chain (sNfL) levels at baseline and follow-up in 530 patients with relapsing MS. Patients were categorized by the presence of oligoclonal IgG bands (OCGB) and intrathecal synthesis of IgG and IgM (intrathecal fraction [IF]: IgG and IgM ). Relationships with the time to first relapse, sNfL concentrations, T2-weighted (T2w) lesions, MS Severity Score (MSSS), and time to initiation of high-efficacy therapy were analyzed in covariate-adjusted statistical models.

Results: By categorical analysis, in patients with IgM the median time to first relapse was 28 months shorter and MSSS on average higher by 1.11 steps compared with patients without intrathecal immunoglobulin synthesis. Moreover, patients with IgM had higher sNfL concentrations, more new/enlarging T2w lesions, and higher total T2w lesion counts (all p ≤ 0.01). These associations were absent or equally smaller in patients who were positive for only OCGB or OCGB/IgG . Furthermore, quantitative analyses revealed that in patients with IgM  ≥ median, the time to first relapse and to initiation of high-efficacy therapy was shorter by 32 and by 203 months, respectively (both p < 0.01), in comparison to patients with IgM  < median. Dose-dependent associations were also found for IgM but not for IgG with magnetic resonance imaging-defined disease activity and sNfL.

Interpretation: This large study supports the value of intrathecal IgM synthesis as an independent biomarker of disease activity and severity in relapsing MS. ANN NEUROL 2021.
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http://dx.doi.org/10.1002/ana.26137DOI Listing
May 2021

Fundamental mechanistic insights from rare but paradigmatic neuroimmunological diseases.

Nat Rev Neurol 2021 Jul 28;17(7):433-447. Epub 2021 May 28.

Infinity, Université Toulouse, CNRS, Inserm, Toulouse, France.

The pathophysiology of complex neuroimmunological diseases, such as multiple sclerosis and autoimmune encephalitis, remains puzzling - various mechanisms that are difficult to dissect seem to contribute, hampering the understanding of the processes involved. Some rare neuroimmunological diseases are easier to study because their presentation and pathogenesis are more homogeneous. The investigation of these diseases can provide fundamental insights into neuroimmunological pathomechanisms that can in turn be applied to more complex diseases. In this Review, we summarize key mechanistic insights into three such rare but paradigmatic neuroimmunological diseases - Susac syndrome, Rasmussen encephalitis and narcolepsy type 1 - and consider the implications of these insights for the study of other neuroimmunological diseases. In these diseases, the combination of findings in humans, different modalities of investigation and animal models has enabled the triangulation of evidence to validate and consolidate the pathomechanistic features and to develop diagnostic and therapeutic strategies; this approach has provided insights that are directly relevant to other neuroimmunological diseases and applicable in other contexts. We also outline how next-generation technologies and refined animal models can further improve our understanding of pathomechanisms, including cell-specific and antigen-specific CNS immune responses, thereby paving the way for the development of targeted therapeutic approaches.
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http://dx.doi.org/10.1038/s41582-021-00496-7DOI Listing
July 2021

Occurrence of status epilepticus in persons with epilepsy is determined by sex, epilepsy classification, and etiology: a single center cohort study.

J Neurol 2021 May 21. Epub 2021 May 21.

Department of Neurology with Institute of Translational Neurology, University of Münster, University Hospital Münster, Albert-Schweitzer-Campus 1, Gebäude A1, 48149, Münster, Germany.

Background: Status epilepticus (SE) can occur in persons with or without epilepsy and is associated with high morbidity and mortality.

Methods: This survey aimed to record self-reported frequency of SE in persons with epilepsy, its association with clinical characteristics and patient level of information on SE and rescue medication. 251 persons with epilepsy at a tertiary epilepsy center were included in the study.

Results: 87 (35%) had a history of SE defined as seizure duration of more than 5 min. These patients were less likely to be seizure-free, and had a higher number of present and past anti-seizure medication. Female sex, cognitive disability, younger age at epilepsy onset, defined epilepsy etiology, and focal epilepsy were associated with a history of SE. On Cox regression analysis, female sex, defined etiology and focal classification remained significant. 67% stated that they had information about prolonged seizures, and 75% knew about rescue medication. 85% found it desirable to receive information about SE at the time of initial diagnosis of epilepsy, but only 16% had been offered such information at the time.

Conclusion: SE is frequent among persons with epilepsy and there remain unmet needs regarding patient education.
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http://dx.doi.org/10.1007/s00415-021-10600-yDOI Listing
May 2021

Characterization of Extracranial Giant Cell Arteritis with Intracranial Involvement and its Rapidly Progressive Subtype.

Ann Neurol 2021 Jul 28;90(1):118-129. Epub 2021 May 28.

Department of Neurology with Institute of Translational Neurology, University of Münster, Münster, Germany.

Objective: The objective of this study was to characterize patients with extracranial giant cell arteritis with intracranial involvement.

Methods: In a multicenter retrospective study, we included 31 patients with systemic giant cell arteritis (GCA) with intracranial involvement. Clinical characteristics, pattern of arterial involvement, and cytokine profiles were assessed. Patients with GCA without intracranial involvement (n = 17), and with intracranial atherosclerosis (n = 25) served as controls.

Results: Erythrocyte sedimentation rate (ESR) was elevated in 18 patients (69.2%) with and in 16 patients (100%) without intracranial involvement (p = 0.02). Headache was complained by 15 patients (50.0%) with and 13 patients (76.5%) without intracranial involvement (p = 0.03). Posterior circulation arteries were affected in 26 patients (83.9%), anterior circulation arteries in 17 patients (54.8%), and both territories in 12 patients (38.7%). Patients with GCA had vertebral artery stenosis proximal and, in contrast, patients with atherosclerosis distal to the origin of posterior inferior cerebellar artery (PICA). Among patients with GCA with intracranial involvement, 11 patients (37.9%) had a rapid progressive disease course characterized by short-term recurrent ischemic events. The median modified Rankin Scale (mRS) at follow-up in these patients was 4 (interquartile range [IQR] = 2.0-6.0) and 4 patients (36.4%) died. Vessel wall expression of IL-6 and IL-17 was significantly increased in patients with rapid progressive course.

Interpretation: Typical characteristics of GCA, headache, and an elevated ESR, are frequently absent in patients with intracranial involvement. However, differentiation of intracranial GCA from atherosclerosis can be facilitated by the typical pattern of vertebral artery stenosis. About one-third of patients with intracranial GCA had a rapid progressive course with poor outcome. IL-17 and IL-6 may represent potential future treatment targets. ANN NEUROL 2021;90:118-129.
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http://dx.doi.org/10.1002/ana.26101DOI Listing
July 2021

Effectiveness and safety of cladribine in MS: Real-world experience from two tertiary centres.

Mult Scler 2021 May 12:13524585211012227. Epub 2021 May 12.

Department of Neurology and Center for Translational and Behavioral Neurosciences (C-TNBS), University Medicine Essen, Essen, Germany.

Background: Oral cladribine has been approved for the treatment of relapsing multiple sclerosis (MS) yet real-world evidence regarding its effectiveness and safety remains scarce.

Objective: To evaluate efficacy and safety outcomes of MS patients following induction of cladribine.

Methods: We evaluated our prospective cohort of cladribine-treated MS patients from two tertiary centres in Germany. Relapses, disability worsening and occurrence of new or enlarging T2-hyperintense magnetic resonance imaging (MRI) lesions were assessed as well as lymphocyte counts and herpes virus infections.

Results: Among 270 patients treated with cladribine, we observed a profound reduction of both relapses and new or enlarging MRI lesions. Treatment appeared more efficacious, especially in patients without previous therapy or following platform substances. Patients switching from natalizumab were prone to re-emerging disease activity. Among patients following dimethyl fumarate pre-treatment, severe lymphopenia was common and associated with increased rates of herpes virus manifestations.

Conclusion: Overall, we observed an efficacy and safety profile of cladribine consistent with data from the phase 3 clinical trial. However, patients switching from natalizumab experienced suboptimal disease control beyond rebound activity following cessation of natalizumab. Furthermore, dimethyl fumarate pre-treatment was associated with a profound risk of developing severe lymphopenia and subsequent herpes virus infections.
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http://dx.doi.org/10.1177/13524585211012227DOI Listing
May 2021

Dietary conjugated linoleic acid links reduced intestinal inflammation to amelioration of CNS autoimmunity.

Brain 2021 May;144(4):1152-1166

Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, Germany.

A close interaction between gut immune responses and distant organ-specific autoimmunity including the CNS in multiple sclerosis has been established in recent years. This so-called gut-CNS axis can be shaped by dietary factors, either directly or via indirect modulation of the gut microbiome and its metabolites. Here, we report that dietary supplementation with conjugated linoleic acid, a mixture of linoleic acid isomers, ameliorates CNS autoimmunity in a spontaneous mouse model of multiple sclerosis, accompanied by an attenuation of intestinal barrier dysfunction and inflammation as well as an increase in intestinal myeloid-derived suppressor-like cells. Protective effects of dietary supplementation with conjugated linoleic acid were not abrogated upon microbiota eradication, indicating that the microbiome is dispensable for these conjugated linoleic acid-mediated effects. Instead, we observed a range of direct anti-inflammatory effects of conjugated linoleic acid on murine myeloid cells including an enhanced IL10 production and the capacity to suppress T-cell proliferation. Finally, in a human pilot study in patients with multiple sclerosis (n = 15, under first-line disease-modifying treatment), dietary conjugated linoleic acid-supplementation for 6 months significantly enhanced the anti-inflammatory profiles as well as functional signatures of circulating myeloid cells. Together, our results identify conjugated linoleic acid as a potent modulator of the gut-CNS axis by targeting myeloid cells in the intestine, which in turn control encephalitogenic T-cell responses.
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http://dx.doi.org/10.1093/brain/awab040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105041PMC
May 2021

Classification of neurological diseases using multi-dimensional cerebrospinal fluid analysis.

Brain 2021 Apr 12. Epub 2021 Apr 12.

Department of Neurology with Institute of Translational Neurology, University and University Hospital Münster, Münster, Germany.

Although cerebrospinal fluid (CSF) analysis routinely enables diagnosis of neurological diseases, it is mainly used for gross distinction between infectious, autoimmune inflammatory, and degenerative central nervous system (CNS) disorders. To investigate, whether a multi-dimensional cellular blood and CSF characterization can support the diagnosis of clinically similar neurological diseases, we analyzed 546 patients with autoimmune neuro-inflammatory, degenerative, or vascular conditions in a cross-sectional retrospective study. By combining feature selection with dimensionality reduction and machine learning approaches we identified pan-disease parameters altered across all autoimmune neuro-inflammatory CNS-diseases and differentiating them from other neurological conditions and inter-autoimmunity classifiers sub-differentiating variants of CNS-directed autoimmunity. Pan-disease as well as diseases-specific changes formed a continuum, reflecting clinical disease evolution. A validation cohort of 231 independent patients confirmed that combining multiple parameters into composite scores can assist classification of neurological patients. Overall, we show that an integrated analysis of blood and CSF parameters improves differential diagnosis of neurological diseases, thereby facilitating early treatment decisions.
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http://dx.doi.org/10.1093/brain/awab147DOI Listing
April 2021

The Innate Immune Response Characterizes Posterior Reversible Encephalopathy Syndrome.

J Clin Immunol 2021 Aug 12;41(6):1229-1240. Epub 2021 Apr 12.

Department of Neurology with Institute of Translational Neurology, University of Münster, Albert-Schweitzer-Campus 1, D-48149, Münster, Germany.

While posterior reversible encephalopathy syndrome (PRES) is often characterized by an inflammatory cerebrospinal-fluid (CSF) profile, knowledge of immune cell patterns in PRES is lacking. Thus, we retrospectively characterized CSF and peripheral blood (PB) from 15 PRES patients, which we analyzed by multidimensional flow cytometry (FC). Results were compared to 72 controls, as well as to 9 patients with progressive multifocal leukoencephalopathy (PML, as a relevant differential diagnosis) and 15 multiple sclerosis patients (MS, as a classical neuroinflammatory disorder), respectively. Total protein level in CSF from PRES patients was elevated compared to that in controls, but not to MS and PML. In-depth FC analysis revealed no differences for adaptive immune cells (B cells, plasma cells, CD4, and CD8 T cells) in PB or CSF of PRES compared to controls. In contrast, we observed alterations of the adaptive immune response in CSF of PML and MS compared to PRES, indicating that the adaptive immune response is not a driver of disease in PRES. Indeed, PRES was characterized by an innate immune response with CD14/CD16 (intermediate) monocytes elevated in PB and CSF, while CD14/CD16 (classical) monocytes were decreased in PB from PRES patients as compared to controls. Levels of CD14/CD16 monocytes correlated with the duration of hospital stay as a surrogate marker for disease severity in PRES patients. Our findings argue for a role of innate rather than adaptive immunity in the pathophysiology of PRES. The observed shift in monocyte subsets might provide valuable diagnostic clues for the clinical management of these patients.
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http://dx.doi.org/10.1007/s10875-021-01033-3DOI Listing
August 2021

Disease-modifying therapies and SARS-CoV-2 vaccination in multiple sclerosis: an expert consensus.

J Neurol 2021 Apr 12. Epub 2021 Apr 12.

MS Center and Neurology Unit, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy.

Coronavirus disease (COVID-19) appeared in December 2019 in the Chinese city of Wuhan and has quickly become a global pandemic. The disease is caused by the severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2), an RNA beta coronavirus phylogenetically similar to SARS coronavirus. To date, more than 132 million cases of COVID19 have been recorded in the world, of which over 2.8 million were fatal ( https://coronavirus.jhu.edu/map.html ). A huge vaccination campaign has started around the world since the end of 2020. The availability of vaccines has raised some concerns among neurologists regarding the safety and efficacy of vaccination in patients with multiple sclerosis (MS) taking immunomodulatory or immunosuppressive therapies.
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http://dx.doi.org/10.1007/s00415-021-10545-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038920PMC
April 2021

Skin Reactions in Patients With Multiple Sclerosis Receiving Cladribine Treatment.

Neurol Neuroimmunol Neuroinflamm 2021 05 9;8(3). Epub 2021 Apr 9.

From the Department of Neurology (L.R., S.P., M.P., T.R., H.W.), Institute of Translational Neurology, University Hospital of Münster, Germany; Department of Neurology (J.H., C.K., R.P.), University Hospital Essen, University Duisburg-Essen, Essen, Germany; Department of Dermatology (W.S.), University Hospital Essen, University Duisburg-Essen, Essen, Germany; and Department of Neurology (M.K., S.G.M.), University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Germany.

Objective: To report 77 patients with multiple sclerosis (MS) who developed skin-related adverse events (AEs) following treatment with cladribine.

Methods: We evaluated our prospective bicentric cladribine cohort. Cladribine-treated patients with a skin AE were identified.

Results: Two hundred thirty-nine cladribine-treated patients with MS were evaluated. Seventy-seven patients (32%) showed at least 1 skin AE at median 1 month after cladribine initiation (range: 1-12). Within first 3 months following last cladribine exposition, hair thinning (n = 28, 12%), skin rash (n = 20; 8%), mucositis (n = 13, 5%), and pruritus (n = 6, 3%) were observed. Furthermore, 35 patients (15%) developed herpes virus infections (time since last cladribine exposition: median 83 [range: 10-305]). In 15 patients, herpes zoster infection was severe (CTCAE grade ≥ 3) and required hospitalization. Delayed skin AEs (≥3 months after a cladribine treatment cycle) involved 1 case of leukocytoclastic vasculitis and 2 cases of alopecia areata. Finally, 2 patients presented with in total 3 isolated precancerous lesions (1 leukoplakia simplex and 2 actinic keratosis) and 1 patient developed a squamous cell carcinoma.

Conclusion: Skin AEs are common in patients with MS treated with cladribine. Until risk management plans have been adjusted to include these phenomena, clinicians should perform a thorough clinical follow-up and in suspicious cases seek early interdisciplinary support. In light of the observed delayed skin reactions, we further emphasize the necessity of careful clinical surveillance of cladribine-treated patients for yet undescribed secondary autoimmune events.

Classification Of Evidence: This study provides Class IV evidence that skin-related AEs are frequent in patients with MS following cladribine in a real-world setting.
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http://dx.doi.org/10.1212/NXI.0000000000000990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042777PMC
May 2021

Zilucoplan: An Investigational Complement C5 Inhibitor for the Treatment of Acetylcholine Receptor Autoantibody-Positive Generalized Myasthenia Gravis.

Expert Opin Investig Drugs 2021 May 1;30(5):483-493. Epub 2021 Apr 1.

Department of Neurology, Institute of Translational Neurology, University of Münster, Münster, Germany.

Introduction: Generalized myasthenia gravis (gMG) is an autoimmune disorder in which pathogenic autoantibodies damage the neuromuscular junction, causing disabling or life-threatening muscle weakness. Most treatments nonspecifically inhibit aspects of the immune system, do not directly address the causal mechanisms of tissue damage, and often have side-effect profiles that negatively impact patients. Understanding of the central pathogenic role of the complement cascade in gMG is advancing, and a new complement-targeting treatment is under investigation.

Areas Covered: We provide an overview of gMG etiology, the complement cascade, current treatments, and the investigational gMG therapy zilucoplan. Zilucoplan is a small, subcutaneously administered, macrocyclic peptide that inhibits cleavage of complement component C5 and the subsequent formation of the membrane attack complex.

Expert Opinion: In a randomized, double-blind, placebo-controlled, phase 2 clinical trial, zilucoplan demonstrated clinically meaningful complement inhibition in patients with acetylcholine receptor-positive gMG. Zilucoplan, a first-of-its-kind cyclic peptide targeting C5, appears to be a therapeutic option for the treatment of gMG based on available pharmacokinetic/pharmacodynamic data and phase 1 and 2 efficacy, safety, and tolerability data with limited long-term follow-up. Zilucoplan use earlier in the treatment paradigm would be suitable in this population should phase 3 efficacy and safety data be equally favorable.
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http://dx.doi.org/10.1080/13543784.2021.1897567DOI Listing
May 2021

Teriflunomide treatment is associated with optic nerve recovery in early multiple sclerosis.

Ther Adv Neurol Disord 2021 6;14:1756286421997372. Epub 2021 Mar 6.

Department of Neurology, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany.

Background And Aims: Various attempts have been made to support recovery following optic neuritis (ON), but the respective trials have mostly been negative. The aim of this study was to determine whether disease-modifying treatment (DMT) following ON as first manifestation of relapsing-remitting multiple sclerosis influences long-term outcomes.

Methods: A total of 79 patients with ON were identified and evaluated at relapse, DMT induction, and 12 months following treatment induction with either glatiramer acetate (GLAT), interferon-beta (IFN), or teriflunomide (TRF). Low-contrast letter acuity (LCLA) and full-field visual-evoked potentials (FF-VEP) were compared between treatment groups using multivariable regression models. The impact of TRF treatment induction compared with IFN or GLAT following relapses outside the optic nerves was evaluated in an independent cohort of 122 patients. Magnetic resonance imaging (MRI) outcomes and rates of confirmed improvement of relapse-related disability were evaluated.

Results: TRF-treated patients exhibited higher LCLA and lower relative P100 latencies normalized to the fellow-eye. Findings were significant following covariate-adjustment by multivariable analyses. Cranial MRI lesion load as well as disability progression rates were not significantly different between groups. The cohort of patients following relapses other than ON showed no differences in confirmed improvement of disability.

Conclusion: TRF treatment is associated with favorable outcomes regarding functional optic nerve recovery following ON in early multiple sclerosis.
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http://dx.doi.org/10.1177/1756286421997372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940774PMC
March 2021

Impact of previous disease-modifying treatment on effectiveness and safety outcomes, among patients with multiple sclerosis treated with alemtuzumab.

J Neurol Neurosurg Psychiatry 2021 Mar 12. Epub 2021 Mar 12.

Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, Germany.

Objectives: Alemtuzumab is effective in patients with active multiple sclerosis but has a complex safety profile, including the development of secondary autoimmunity. Most of patients enrolled in randomised clinical trials with alemtuzumab were either treatment naïve or pretreated with injectable substances. Other previous disease-modifying treatments (DMTs) were not used in the study cohorts, and therefore, associated risks might yet remain unidentified.

Methods: We retrospectively evaluated a prospective dual-centre alemtuzumab cohort of 170 patients. We examined the baseline characteristics as well as safety and effectiveness outcomes, including the time to first relapse, the time to 3 months confirmed disability worsening and the time to secondary autoimmunity.

Results: The regression analysis showed that, among all previously used DMTs, the pretreatment with fingolimod (n=33 HRs for the time to first relapse (HR 5.420, 95% CI 2.520 to 11.660; p<0.001)) and for the time to worsening of disability (HR 7.676, 95% CI 2.870 to 20.534; p<0.001). Additionally, patients pretreated with fingolimod were more likely to experience spinal relapses (55% vs 10% among previously naïve patients; p<0.001) and had an increased risk of secondary autoimmunity (HR 5.875, 95% CI 2.126 to 16.27; p<0.001).

Conclusion: In the real-world setting, we demonstrated suboptimal disease control and increased risk of secondary autoimmunity following alemtuzumab, among patients previously treated with fingolimod. These data can provide guidance for improving MS therapeutic management.
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http://dx.doi.org/10.1136/jnnp-2020-325304DOI Listing
March 2021

Predictors, outcome and characteristics of oropharyngeal dysphagia in idiopathic inflammatory myopathy.

Muscle Nerve 2021 06 24;63(6):874-880. Epub 2021 Mar 24.

Department of Neurology with Institute of Translational Neurology, University of Muenster, Muenster, Germany.

Introduction: Oropharyngeal dysphagia is a clinical hallmark of idiopathic inflammatory myopathy (IIM). This study investigated predictors, outcome, and characteristics of oropharyngeal dysphagia in patients with different types of IIM.

Methods: Flexible endoscopic evaluation of swallowing (FEES) videos of 71 IIM patients were retrospectively analyzed for bolus spillage, penetration, aspiration, and pharyngeal residue. Based on these findings, dysphagia severity was rated. Regression analyses were performed to investigate demographic and disease-specific predictors of dysphagia severity and pneumonia as outcome-relevant complications of dysphagia. A score was developed to rate the quality of the endoscopic white-out as a surrogate marker for pharyngeal muscle weakness with consecutive residue.

Results: Our analysis revealed no independent predictors of dysphagia severity. Dysphagia severity, however, was an independent predictor for pneumonia, which occurred in 24% of patients. Pharyngeal residue with risk of postdeglutitive aspiration was the most common dysphagia pattern. Attenuation of the endoscopic white-out was related to residue severity.

Discussion: Dysphagia in IIM assessed with FEES is associated with relevant complications, such as aspiration pneumonia, and must be considered independently of peripheral muscle weakness and disease duration. Swallowing impairment mainly presents with pharyngeal residue. The quality of the white-out may serve as a semi-quantitative surrogate marker for pharyngeal contractility.
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http://dx.doi.org/10.1002/mus.27225DOI Listing
June 2021

Expiratory Muscle Strength Training for Therapy of Pharyngeal Dysphagia in Parkinson's Disease.

Mov Disord 2021 Mar 2. Epub 2021 Mar 2.

Department of Neurology with Institute of Translational Neurology, University Hospital of Muenster, Muenster, Germany.

Background: Pharyngeal dysphagia in Parkinson's disease (PD) is a common and clinically relevant symptom associated with poor nutrition intake, reduced quality of life, and aspiration pneumonia. Despite this, effective behavioral treatment approaches are rare.

Objective: The objective of this study was to verify if 4 week of expiratory muscle strength training can improve pharyngeal dysphagia in the short and long term and is able to induce neuroplastic changes in cortical swallowing processing.

Methods: In this double-blind, randomized, controlled trial, 50 patients with hypokinetic pharyngeal dysphagia, as confirmed by flexible endoscopic evaluation of swallowing, performed a 4-week expiratory muscle strength training. Twenty-five participants used a calibrated ("active") device, 25 used a sham handheld device. Swallowing function was evaluated directly before and after the training period, as well as after a period of 3 month using flexible endoscopic evaluation of swallowing. Swallowing-related cortical activation was measured in 22 participants (active:sham; 11:11) using whole-head magnetencephalography.

Results: The active group showed significant improvement in the flexible endoscopic evaluation of swallowing-based dysphagia score after 4 weeks and after 3 months, whereas in the sham group no significant changes from baseline were observed. Especially, clear reduction in pharyngeal residues was found. Regarding the cortical swallowing network before and after training, no statistically significant differences were found by magnetencephalography examination.

Conclusions: Four-week expiratory muscle strength training significantly reduces overall dysphagia severity in PD patients, with a sustained effect after 3 months compared with sham training. This was mainly achieved by improving swallowing efficiency. The treatment effect is probably caused by peripheral mechanisms, as no changes in the cortical swallowing network were identified. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28552DOI Listing
March 2021

Impact of complement activation on clinical outcomes in multiple sclerosis.

Ann Clin Transl Neurol 2021 04 1;8(4):944-950. Epub 2021 Mar 1.

Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, 48149, Germany.

We determined activation profiles of the classical and alternative complement pathway in 39 treatment-naïve patients with early relapse-onset MS. Plasma concentrations of complement fragments were unchanged in MS compared to 32 patients with non-inflammatory neurological diseases. Profiles in patients experiencing clinical exacerbations did not differ from patients with stable disease and did not correlate with baseline EDSS, numbers of T2 lesions and time to second relapse. Long-term EDSS outcomes 4 years after diagnosis did not significantly correlate with baseline complement levels. These data do not support the use of complement activation products as biomarkers for disease activity in early MS.
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http://dx.doi.org/10.1002/acn3.51334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045986PMC
April 2021

Intravenous methadone causes acute toxic and delayed inflammatory encephalopathy with persistent neurocognitive impairments.

BMC Neurol 2021 Feb 22;21(1):85. Epub 2021 Feb 22.

Department of Neurology with Institute of Translational Neurology, University Hospital Muenster, Albert-Schweitzer-Campus 1, A1, 48149, Münster, Germany.

Background: The mu-opioid agonist methadone is administered orally and used in opioid detoxification and in the treatment of moderate-to-severe pain. Acute oral methadone-use and -abuse have been associated with inflammatory and toxic central nervous system (CNS) damage in some cases and cognitive deficits can develop in long-term methadone users. In contrast, reports of intravenous methadone adverse effects are rare.

Case Presentation: Here, we report a patient who developed acute bilateral hearing loss, ataxia and paraparesis subsequently to intravenous methadone-abuse. While the patient gradually recovered from these deficits, widespread magnetic resonance imaging changes progressed and delayed-onset encephalopathy with signs of cortical dysfunction persisted. This was associated with changes in the composition of monocyte and natural killer cell subsets in the cerebrospinal fluid.

Conclusion: This case suggests a potential bi-phasic primary toxic and secondary inflammatory CNS damage induced by intravenous methadone.
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http://dx.doi.org/10.1186/s12883-021-02108-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898738PMC
February 2021

Serum neurofilament light and tau as prognostic markers for all-cause mortality in the elderly general population-an analysis from the MEMO study.

BMC Med 2021 02 15;19(1):38. Epub 2021 Feb 15.

Institute of Epidemiology and Social Medicine, University of Münster, Domagkstraße 3, 48149, Münster, Germany.

Background: Neurofilament light chain (NfL) is a cytoskeletal protein component whose release into blood is indicative of neuronal damage. Tau is a microtubule-associated protein in neurons and strongly associated with overall brain degeneration. NfL and tau levels are associated with mortality in different neurological diseases, but studies in the general population are missing. We investigated whether NfL and tau serum levels could serve as prognostic markers for overall mortality in elderly individuals without pre-defined neurological conditions. Further, we investigated the cross-sectional associations between NfL, tau, neuropsychological functioning, and brain structures.

Methods: In 1997, 385 inhabitants of Augsburg who were aged 65 years and older were included in the Memory and Morbidity in Augsburg Elderly (MEMO) study. They participated in a face-to-face medical interview including neuropsychological tests and magnetic resonance imaging (MRI) of the brain. NfL and tau were measured from non-fasting blood samples using highly sensitive single molecule array assays. To assess the prognostic accuracy of the biomarkers, concordance statistics based on the predicted 5-year survival probabilities were calculated for different Cox regression models. Associations between the biomarkers and the neuropsychological test scores or brain structures were investigated using linear or logistic regression.

Results: NfL (HR 1.27, 95% CI [1.14-1.42]) and tau (1.20 [1.07-1.35]) serum levels were independently associated with all-cause mortality. NfL, but not tau, increased the prognostic accuracy when added to a model containing sociodemographic characteristics (concordance statistic 0.684 [0.612-0.755] vs. 0.663 [0.593-0.733]), but not when added to a model containing sociodemographic characteristics and brain atrophy or neuropsychological test scores. NfL serum levels were cross-sectionally associated with neuropsychological test scores and brain structures.

Conclusions: The association between NfL serum levels and brain atrophy and neuropsychological performance in individuals without overt neurological disease is similar to that seen in patients with neurodegenerative diseases. These findings support the concept of a continuum of physiological aging and incipient, subclinical pathology, and manifest disease. NfL, but not tau, serum levels might serve as a prognostic marker for all-cause mortality if no other clinical information is available.
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http://dx.doi.org/10.1186/s12916-021-01915-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883435PMC
February 2021

Characterisation of MS phenotypes across the age span using a novel data set integrating 34 clinical trials (NO.MS cohort): Age is a key contributor to presentation.

Mult Scler 2021 Jan 28:1352458520988637. Epub 2021 Jan 28.

Department of Neurology, University Hospital Münster, Münster, Germany.

Background: The Oxford Big Data Institute, multiple sclerosis (MS) physicians and Novartis aim to address unresolved questions in MS with a novel comprehensive clinical trial data set.

Objective: The objective of this study is to describe the Novartis-Oxford MS (NO.MS) data set and to explore the relationships between age, disease activity and disease worsening across MS phenotypes.

Methods: We report key characteristics of NO.MS. We modelled MS lesion formation, relapse frequency, brain volume change and disability worsening cross-sectionally, as a function of patients' baseline age, using phase III study data (≈8000 patients).

Results: NO.MS contains data of ≈35,000 patients (>200,000 brain images from ≈10,000 patients), with >10 years follow-up. (1) Focal disease activity is highest in paediatric patients and decreases with age, (2) brain volume loss is similar across age and phenotypes and (3) the youngest patients have the lowest likelihood (<25%) of disability worsening over 2 years while risk is higher (25%-75%) in older, disabled or progressive MS patients. Young patients benefit most from treatment.

Conclusion: NO.MS will illuminate questions related to MS characterisation, progression and prognosis. Age modulates relapse frequency and, thus, the phenotypic presentation of MS. Disease worsening across all phenotypes is mediated by age and appears to some extent be independent from new focal inflammatory activity.
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http://dx.doi.org/10.1177/1352458520988637DOI Listing
January 2021

Immune Cell Infiltration into the Brain After Ischemic Stroke in Humans Compared to Mice and Rats: a Systematic Review and Meta-Analysis.

Transl Stroke Res 2021 Jan 26. Epub 2021 Jan 26.

Department of Neurology with Institute of Translational Neurology, University of Münster, Albert-Schweitzer-Campus 1, Gebäude A1, 48149, Münster, Germany.

Although several studies have suggested that anti-inflammatory strategies reduce secondary infarct growth in animal stroke models, clinical studies have not yet demonstrated a clear benefit of immune modulation in patients. Potential reasons include systematic differences of post-ischemic neuroinflammation between humans and rodents. We here performed a systematic review and meta-analysis to summarize and compare the spatial and temporal distribution of immune cell infiltration in human and rodent stroke. Data on spatiotemporal distribution of immune cells (T cells, macrophages, and neutrophils) and infarct volume were extracted. Data from all rodent studies were pooled by means of a random-effect meta-analysis. Overall, 20 human and 188 rodent stroke studies were included in our analyses. In both patients and rodents, the infiltration of macrophages and neutrophils preceded the lymphocytic influx. Macrophages and neutrophils were the predominant immune cells within 72 h after infarction. Although highly heterogeneously across studies, the temporal profile of the poststroke immune response was comparable between patients and rodents. In rodent stroke, the extent of the immune cell infiltration depended on the duration and location of vessel occlusion and on the species. The density of infiltrating immune cells correlated with the infarct volume. In summary, we provide the first systematic analysis and comparison of human and rodent post-ischemic neuroinflammation. Our data suggest that the inflammatory response in rodent stroke models is comparable to that in patients with stroke. However, the overall heterogeneity of the post-ischemic immune response might contribute to the translational failure in stroke research.
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http://dx.doi.org/10.1007/s12975-021-00887-4DOI Listing
January 2021
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