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Multiple Sclerosis: HELP
Articles by Hans Peter Hartung
Based on 192 articles published since 2009
(Why 192 articles?)
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Between 2009 and 2019, H-P Hartung wrote the following 192 articles about Multiple Sclerosis.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8
1 Guideline Recommendations for a Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS). 2012

Langdon, D W / Amato, M P / Boringa, J / Brochet, B / Foley, F / Fredrikson, S / Hämäläinen, P / Hartung, H-P / Krupp, L / Penner, I K / Reder, A T / Benedict, R H B. ·Royal Holloway, University of London, Surrey, UK. d.langdon@rhul.ac.uk ·Mult Scler · Pubmed #22190573.

ABSTRACT: BACKGROUND: Cognitive impairment in MS impacts negatively on many patients at all disease stages and in all subtypes. Full clinical cognitive assessment is expensive, requiring expert staff and special equipment. Test versions and normative data are not available for all languages and cultures. OBJECTIVE: To recommend a brief cognitive assessment for multiple sclerosis (MS) that is optimized for small centers, with one or few staff members, who may not have neuropsychological training and constructed to maximize international use. METHODS: An expert committee of twelve members representing the main cultural groups that have so far contributed considerable data about MS cognitive dysfunction was convened. Following exhaustive literature review, peer-reviewed articles were selected to cover a broad spectrum of cultures and scales that targeted cognitive domains vulnerable to MS. Each was rated by two committee members and candidates scales were rated on psychometric qualities (reliability, validity, and sensitivity), international application, ease of administration, feasibility in the specified context, and acceptability to patients. RESULTS: The committee recommended the Symbol Digit Modalities Test, if only 5 minutes was available, with the addition of the California Verbal Learning Test - Second Edition and the Brief Visuospatial Memory Test - Revised learning trials if a further 10 minutes could be allocated for testing. CONCLUSIONS: A brief cognitive assessment for MS has been recommended. A validation protocol has been prepared for language groups and validation studies have commenced.

2 Editorial Reconstitution of the peripheral immune repertoire following withdrawal of fingolimod. 2017

Warnke, Clemens / Graf, Jonas / Hartung, Hans-Peter. ·Department of Neurology, University Hospital of Cologne, Cologne, Germany. · Department of Neurology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany. ·Mult Scler · Pubmed #28749310.

ABSTRACT: -- No abstract --

3 Editorial Natalizumab-associated progressive multifocal leukoencephalopathy is not preceded by elevated drug concentrations. 2017

Warnke, Clemens / Hartung, Hans-Peter. ·Department of Neurology, University Hospital Cologne, Cologne, Germany. · Department of Neurology, Medical Faculty, Heinrich-Heine-Universität Düsseldor, Düsseldorf, Germany. ·Mult Scler · Pubmed #28481191.

ABSTRACT: -- No abstract --

4 Editorial Targeting semaphorins in MS as a treatment strategy to promote remyelination: A tale of mice, rats and men. 2015

Kremer, David / Hartung, Hans-Peter / Küry, Patrick. ·Department of Neurology, Heinrich-Heine University, Germany. · Department of Neurology, Heinrich-Heine University, Germany hans-peter.hartung@uni-duesseldorf.de. ·Mult Scler · Pubmed #26432852.

ABSTRACT: -- No abstract --

5 Editorial Switching from natalizumab to fingolimod: A randomized, placebo-controlled study in RRMS. 2015

Kappos, Ludwig / Radue, Ernst-Wilhelm / Comi, Giancarlo / Montalban, Xavier / Butzkueven, Helmut / Wiendl, Heinz / Giovannoni, Gavin / Hartung, Hans-Peter / Derfuss, Tobias / Naegelin, Yvonne / Sprenger, Till / Mueller-Lenke, Nicole / Griffiths, Sarah / von Rosenstiel, Philipp / Gottschalk, Rebecca / Zhang, Ying / Dahlke, Frank / Tomic, Davorka / Anonymous981006. ·From Neurology, the Departments of Medicine, Clinical Research and Biomedicine (L.K., T.D., Y.N., T.S.), the Medical Image Analysis Center (MIAC) (E.-W.R., T.S., N.M.-L.), and the Department of Radiology, Division of Neuroradiology (T.S.), University Hospital, University of Basel, Switzerland · the Department of Neuroscience (G.C.), Scientific Institute H. San Raffaele, University of Milan, Italy · Vall d'Hebron University Hospital (X.M.), Barcelona, Spain · Royal Melbourne Hospital (H.B.), Parkville, Australia · the Department of Neurology (H.W.), University of Münster, Germany · the Neuroscience and Trauma Centre (G.G.), Blizard Institute, Barts and The London School of Medicine and Dentistry, London, UK · the Department of Neurology (H.-P.H.), Heinrich Heine University, Düsseldorf, Germany · Oxford PharmaGenesis Ltd. (S.G.), Tubney Warren Barns, Oxford, UK · Novartis Pharma AG (P.v.R., Y.Z., F.D., D.T.), Basel, Switzerland · and Novartis Pharmaceutical Corporation (R.G.), East Hanover, NJ. ·Neurology · Pubmed #26024899.

ABSTRACT: OBJECTIVE: To investigate the effect of different natalizumab washout (WO) periods on recurrence of MRI and clinical disease activity in patients switching from natalizumab to fingolimod. METHODS: In this multicenter, double-blind, placebo-controlled trial (TOFINGO), patients with relapsing-remitting multiple sclerosis (RRMS) were randomized 1:1:1 to 8-, 12-, or 16-week WO followed by fingolimod treatment over 32 weeks from last natalizumab infusion (LNI). Brain MRI was performed at baseline and weeks 8, 12, 16, 20, and 24. RESULTS: Of 142 enrolled and randomized patients, 112 (78.9%) completed the study (8 weeks, n = 41/50; 12 weeks, n = 31/42; 16 weeks, n = 40/50). Number (95% confidence interval [CI]) of active (new/newly enlarged T2) lesions from LNI through 8 weeks of fingolimod treatment (primary outcome) was similar in the 8-week (2.1 [1.7-2.6]) and 12-week WO groups (1.7 [1.3-2.2]) and higher in the 16-week WO group (8.2 [7.3-9.1]). During the WO period only, the number (95% CI) of active lesions increased with increasing WO duration (8 weeks, 0.4 [0.2-0.6]; 12 weeks, 2.1 [1.6-2.6]; 16 weeks, 3.6 [3.0-4.2]). Over the 24 weeks from LNI, gadolinium-enhancing T1 lesion counts were lower in the 8-week WO group (14.1 [5.67-22.53]) than in the 12-week (21.3 [1.41-41.19]) or 16-week (18.5 [8.40-28.60]) WO groups. More patients were relapse-free in the 8-week (88%) and 12-week (91%) WO groups than the 16-week WO group (84%). Sixty-eight percent of patients experienced adverse events (mostly mild/moderate), with similar incidence across groups. No unusually severe relapses or opportunistic infections occurred. CONCLUSIONS: Initiating fingolimod therapy 8-12 weeks after natalizumab discontinuation is associated with a lower risk of MRI and clinical disease reactivation than initiation after 16-week WO. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with RRMS switching from natalizumab to fingolimod, shorter natalizumab WO periods are associated with less MRI disease activity than are longer WO periods.

6 Editorial The new therapeutic landscape in multiple sclerosis: exciting times and new perspectives. 2014

Hartung, Hans-Peter / Kieseier, Bernd C. ·Department of Neurology, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany. ·Curr Opin Neurol · Pubmed #24751962.

ABSTRACT: -- No abstract --

7 Editorial Risks and benefits of multiple sclerosis therapies: need for continual assessment? 2011

Kieseier, Bernd C / Wiendl, Heinz / Hartung, Hans-Peter / Leussink, Verena-Isabell / Stüve, Olaf. · ·Curr Opin Neurol · Pubmed #21483261.

ABSTRACT: PURPOSE OF REVIEW: The aim is to describe and discuss the ongoing debate on how to balance an increase in clinical efficacy against a heightened risk of developing serious side-effects, as has surfaced recently with some novel therapies for relapsing forms of multiple sclerosis. RECENT FINDINGS: New therapies are emerging that differ with regard to their mechanism of action, their mode of administration, their side-effect profile and the clinical benefits that they offer to patients in comparison with established therapeutic modalities in multiple sclerosis. Treating physicians will need to make choices on the best treatments for their patients on the basis of limited experience. This process requires optimal assessment of risks and benefits. SUMMARY: Careful assessment of the risk-benefit profile of the various options may allow treatment choices and perhaps ensure that patients obtain the most benefit from treatment without being exposed to unnecessary risk.

8 Editorial Beyond axonal transection: hippocampal damage in multiple sclerosis. 2011

Aktas, Orhan / Hartung, Hans-Peter. · ·Ann Neurol · Pubmed #21446019.

ABSTRACT: -- No abstract --

9 Editorial Bioavailability of interferon-beta in patients with multiple sclerosis - fishing for the surrogate. 2010

Kieseier, B C / Hartung, H-P. · ·Eur J Neurol · Pubmed #20050905.

ABSTRACT: -- No abstract --

10 Editorial Bleak prospects for primary progressive multiple sclerosis therapy: downs and downs, but a glimmer of hope. 2009

Hartung, Hans-Peter / Aktas, Orhan. · ·Ann Neurol · Pubmed #19847907.

ABSTRACT: -- No abstract --

11 Review Monoclonal Antibodies for Multiple Sclerosis: An Update. 2019

Graf, Jonas / Aktas, Orhan / Rejdak, Konrad / Hartung, Hans-Peter. ·Department of Neurology, University Hospital, Medical Faculty Heinrich-Heine-University, Moorenstraße 5, 40225, Düsseldorf, Germany. · Department of Neurology, Medical University of Lublin, Lublin, Poland. · Department of Neurology, University Hospital, Medical Faculty Heinrich-Heine-University, Moorenstraße 5, 40225, Düsseldorf, Germany. hans-peter.hartung@uni-duesseldorf.de. ·BioDrugs · Pubmed #30604390.

ABSTRACT: The use of monoclonal antibodies in multiple sclerosis (MS) patients is in a transitional period. Studies regarding well-established, effective antibodies such as natalizumab and alemtuzumab focus more and more on long-term efficacy and safety, risk management, and treating complications. Primary progressive MS, a disease that was long considered to be unmodifiable, is currently in focus following ocrelizumab being approved as the first drug with a proven beneficial effect on the disease course. Conversely, post-marketing safety mechanisms have also proven to function as daclizumab has been suspended after a series of relevant serious adverse events. Currently, new therapies are emerging that promise more convenience and an improved safety profile (ofatumumab) or remyelinating potential with clinical improvement (opicinumab). While it is very unlikely that monoclonal antibodies will ever cure MS, they have become very valuable therapeutic tools to better patient outcomes. This review focuses on developments of monoclonal antibodies used in the past, present, and near future in MS patients.

12 Review Human Endogenous Retroviruses in Neurological Diseases. 2018

Küry, Patrick / Nath, Avindra / Créange, Alain / Dolei, Antonina / Marche, Patrice / Gold, Julian / Giovannoni, Gavin / Hartung, Hans-Peter / Perron, Hervé. ·Department of Neurology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany. · Section of infections of the Nervous System, National Institute of Neurological Diseases and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, MD, USA. · Service de Neurologie, Groupe Hospitalier Henri Mondor, Assistance Publique Hopitaux de Paris (APHP), Université Paris Est, Créteil, France. · Department of Virology, University of Sassari, Sassari, Italy. · Institute for Advanced Biosciences (IAB), University of Grenoble-Alpes, La Tronche, France; Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 1209, La Tronche, France. · Centre for Neuroscience and Trauma, Blizard Institute, Queen Mary University, London, UK; The Albion Centre, Prince of Wales Hospital, Sydney, Australia. · Centre for Neuroscience and Trauma, Blizard Institute, Queen Mary University, London, UK. · Department of Neurology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany. Electronic address: hans-peter.hartung@uni-duesseldorf.de. · Geneuro, Plan les Ouates, Geneva, Switzerland; University of Lyon, Lyon, France. ·Trends Mol Med · Pubmed #29551251.

ABSTRACT: The causes of multiple sclerosis and amyotrophic lateral sclerosis have long remained elusive. A new category of pathogenic components, normally dormant within human genomes, has been identified: human endogenous retroviruses (HERVs). These represent ∼8% of the human genome, and environmental factors have reproducibly been shown to trigger their expression. The resulting production of envelope (Env) proteins from HERV-W and HERV-K appears to engage pathophysiological pathways leading to the pathognomonic features of MS and ALS, respectively. Pathogenic HERV elements may thus provide a missing link in understanding these complex diseases. Moreover, their neutralization may represent a promising strategy to establish novel and more powerful therapeutic approaches.

13 Review Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. 2018

Thompson, Alan J / Banwell, Brenda L / Barkhof, Frederik / Carroll, William M / Coetzee, Timothy / Comi, Giancarlo / Correale, Jorge / Fazekas, Franz / Filippi, Massimo / Freedman, Mark S / Fujihara, Kazuo / Galetta, Steven L / Hartung, Hans Peter / Kappos, Ludwig / Lublin, Fred D / Marrie, Ruth Ann / Miller, Aaron E / Miller, David H / Montalban, Xavier / Mowry, Ellen M / Sorensen, Per Soelberg / Tintoré, Mar / Traboulsee, Anthony L / Trojano, Maria / Uitdehaag, Bernard M J / Vukusic, Sandra / Waubant, Emmanuelle / Weinshenker, Brian G / Reingold, Stephen C / Cohen, Jeffrey A. ·Faculty of Brain Sciences, University College London, London, UK. · Division of Neurology, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. · Institute of Healthcare Engineering, University College London, London, UK; Institute of Neurology, University College London, London, UK; Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, Netherlands. · Neurology Department, Sir Charles Gairdner Hospital, Perth, WA, Australia. · National Multiple Sclerosis Society, New York, NY, USA. · Department of Neurology, Vita-Salute San Raffaele University-Ospedale San Raffaele, Milan, Italy. · Institute for Neurological Research Dr. Raúl Carrea, FLENI, Buenos Aires, Argentina. · Department of Neurology, Medical University of Graz, Graz, Austria. · The Neuroimaging Research Unit, San Raffaele Scientific Institute, Vita-Salute San Raffaele University-Ospedale San Raffaele, Milan, Italy. · Department of Medicine, The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada. · Department of Multiple Sclerosis Therapeutics, School of Medicine, Fukushima Medical University, Fukushima, Japan; Multiple Sclerosis and Neuromyelitis Optica Center, Southern TOHOKU Research Institute for Neuroscience, Koriyama, Fukushima, Japan. · Department of Neurology, New York University Langone Medical Center, New York, NY, USA. · Department of Neurology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany. · Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital and University of Basel, Basel, Switzerland. · Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai, New York, NY, USA. · Departments of Internal Medicine and Community Health Sciences, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada. · Queen Square Multiple Sclerosis Centre, University College London, London, UK. · Centre d'Esclerosi Múltiple de Catalunya, Vall d'Hebron University Hospital, Barcelona, Spain; Division of Neurology, University of Toronto, St Michael's Hospital, Toronto, ON, Canada. · Department of Neurology, Johns Hopkins University, Baltimore, MD, USA. · Danish Multiple Sclerosis Center, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark. · Centre d'Esclerosi Múltiple de Catalunya, Vall d'Hebron University Hospital, Barcelona, Spain. · Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada. · Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, Bari, Italy. · Department of Neurology, VU University Medical Center, Amsterdam, Netherlands. · Service de neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-inflammation, Hôpital Neurologique, Hospices Civils de Lyon, Bron, France; Centre des Neurosciences de Lyon, INSERM 1028 et CNRS UMR5292, Lyon, France; Université Claude Bernard Lyon 1, Faculté de Médecine Lyon-Est, Villeurbanne, Auvergne-Rhône-Alpes, France. · Department of Neurology, University of California at San Francisco, San Francisco, CA, USA. · Department of Neurology, Mayo Clinic, Rochester, MN, USA. · Scientific and Clinical Review Associates LLC, Salisbury, CT, USA. · Neurologic Institute, Cleveland Clinic, Cleveland, OH, USA. Electronic address: cohenj@ccf.org. ·Lancet Neurol · Pubmed #29275977.

ABSTRACT: The 2010 McDonald criteria for the diagnosis of multiple sclerosis are widely used in research and clinical practice. Scientific advances in the past 7 years suggest that they might no longer provide the most up-to-date guidance for clinicians and researchers. The International Panel on Diagnosis of Multiple Sclerosis reviewed the 2010 McDonald criteria and recommended revisions. The 2017 McDonald criteria continue to apply primarily to patients experiencing a typical clinically isolated syndrome, define what is needed to fulfil dissemination in time and space of lesions in the CNS, and stress the need for no better explanation for the presentation. The following changes were made: in patients with a typical clinically isolated syndrome and clinical or MRI demonstration of dissemination in space, the presence of CSF-specific oligoclonal bands allows a diagnosis of multiple sclerosis; symptomatic lesions can be used to demonstrate dissemination in space or time in patients with supratentorial, infratentorial, or spinal cord syndrome; and cortical lesions can be used to demonstrate dissemination in space. Research to further refine the criteria should focus on optic nerve involvement, validation in diverse populations, and incorporation of advanced imaging, neurophysiological, and body fluid markers.

14 Review Benefit-Risk Profile of Sphingosine-1-Phosphate Receptor Modulators in Relapsing and Secondary Progressive Multiple Sclerosis. 2017

Comi, Giancarlo / Hartung, Hans-Peter / Bakshi, Rajesh / Williams, Ian M / Wiendl, Heinz. ·Department of Neurology and INSPE, Scientific Institute Hospital San Raffaele, Vita-Salute San Raffaele University, Milan, Italy. comi.giancarlo@hsr.it. · Department of Neurology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany. · Center for Neuropsychiatry, LVR Klinikum, Düsseldorf, Germany. · Novartis Pharma AG, Basel, Switzerland. · Oxford PharmaGenesis Ltd, Oxford, UK. · Department of Neurology, University Hospital Münster, Münster, Germany. ·Drugs · Pubmed #28905255.

ABSTRACT: Since the approval of fingolimod, several selective sphingosine-1-phosphate receptor modulators have entered clinical development for multiple sclerosis. However, side effects can occur with sphingosine-1-phosphate receptor modulators. By considering short-term data across the drug class and longer term fingolimod data, we aim to highlight the potential of sphingosine-1-phosphate receptor modulators in multiple sclerosis, while offering reassurance that their benefit-risk profiles are suitable for long-term therapy. Short-term fingolimod studies demonstrated the efficacy of this drug class, showed that cardiac events upon first-dose administration are transient and manageable, and showed that serious adverse events are rare. Early-phase studies of selective sphingosine-1-phosphate receptor modulators also show efficacy with a similar or improved safety profile, and treatment initiation effects were reduced with dose titration. Longer term fingolimod studies demonstrated sustained efficacy and raised no new safety concerns, with no increases in macular edema, infection, or malignancy rates. Switch studies identified no safety concerns and greater patient satisfaction and persistence with fingolimod when switching from injectable therapies with no washout period. Better outcomes were seen with short than with long washouts when switching from natalizumab. The specific immunomodulatory effects of sphingosine-1-phosphate receptor modulators are consistent with the low observed rates of long-term, drug-related adverse effects with fingolimod. Short-term data for selective sphingosine-1-phosphate receptor modulators support their potential effectiveness in multiple sclerosis, and improved side-effect profiles may widen patient access to this drug class. The long-term safety, tolerability, and persistence profiles of fingolimod should reassure clinicians that sphingosine-1-phosphate receptor modulators are likely to be suitable for the long-term treatment of multiple sclerosis.

15 Review Interdisciplinary Risk Management in the Treatment of Multiple Sclerosis. 2016

Havla, Joachim / Warnke, Clemens / Derfuss, Tobias / Kappos, Ludwig / Hartung, Hans-Peter / Hohlfeld, Reinhard. ·Institute for Clinical Neuroimmunology, Biomedical Center and Hospital, Ludwig-Maximilians Universität München, Munich; Department of Neurology, Faculty of Medicine, Heinrich Heine University Düsseldorf; Department of Neurology, University Hospital Basel; Munich Cluster for Systems Neurology (SyNergy). ·Dtsch Arztebl Int · Pubmed #28130920.

ABSTRACT: BACKGROUND: Multiple sclerosis (MS) is the most common autoimmune disease of the central nervous system. There are at least 150 000 persons with MS in Germany. Recent years have seen the approval of new drugs against. METHODS: This article is based on pertinent literature retrieved by a selective search in PubMed as well as on documentation of relevant risks and adverse effects in "red hand letters" (information bulletins from pharmaceutical companies to physicians about adverse drug effects) and elsewhere, along with data provided by the German Multiple Sclerosis Competence Network. RESULTS: In recent years, there have been major advances enabling better, more individualized treatment of patients with MS. Physicians must, however, give due consideration to potentially severe or even life-threatening adverse drug effects. These can include, for example, transaminase elevation (hepatotoxicity), cardio- and nephrotoxicity, or lympho- and leukopenia with a variable risk of infection. Among patients taking natalizumab, the cumulative risk of developing progressive multifocal leukencephalopathy (PML) may be 1:100 or higher, depending on the individual risk profile. Rare cases of PML have also been seen under treatment with fingolimod and dimethyl fumarate. Moreover, any type of immunosuppressive treatment can, at least theoretically, increase the risk of malignant disease. Secondary autoimmune diseases can arise as well: approximately 35% of patients treated with alemtuzumab develop autoimmune thyroid disease within two years, and 2% of patients who take daclizumab have severe autoimmune dermatological side effects. Teriflunomide, fingolimod, natalizumab, mitoxantrone, interferon β1-a/b, and daclizumab can all damage the liver. There are also psychiatric, reproductive, and vaccineassociated risks and side effects that must be considered. CONCLUSION: Newer drugs for MS have enabled more effective treatment, but are also associated with a higher risk of side effects. Interdisciplinary risk management is needed.

16 Review Ocrelizumab for the treatment of relapsing-remitting multiple sclerosis. 2016

Menge, Til / Dubey, Divyanshu / Warnke, Clemens / Hartung, Hans-Peter / Stüve, Olaf. ·a Department of Neurology , Heinrich-Heine University Düsseldorf , Düsseldorf , Germany. · b Department of Neurology , LVR-Klinikum Düsseldorf , Düsseldorf , Germany. · c Department of Neurology and Neurotherapeutics , UT Southwestern Medical Center , Dallas , TX , USA. · d Neurology Section , VA North Texas Health Care System, Medical Service , Dallas , TX , USA. ·Expert Rev Neurother · Pubmed #27552111.

ABSTRACT: INTRODUCTION: Despite recent advances in pharmacological management, multiple sclerosis (MS), an autoimmune disease of the central nervous system, remains a leading cause of disability. In relapsing-remitting (RR)MS, neurologists most commonly utilize immunomodulatory or immunosuppressive agents to benefit their patients. With the introduction of humanized monoclonal antibodies (mAbs) ablation of distinct immune populations has become possible. Depletion of B cells by anti-CD20 mAbs has repeatedly proven to be a very rapid and effective means to diminish disease activity in RRMS. AREAS COVERED: We discuss the biological rationale, development, and recent clinical study results of the second generation anti-CD20 mAb ocrelizumab. Expert commentary: The topline results of two phase-III randomized clinical trials demonstrate superiority of ocrelizumab over interferon beta in RRMS patients with regards to clinical and paraclinical outcome parameters. The short term adverse events profile appears favorable. However, long-term effects of repeated B cell depletion are currently unknown.

17 Review Pharmacological management of spasticity in multiple sclerosis: Systematic review and consensus paper. 2016

Otero-Romero, Susana / Sastre-Garriga, Jaume / Comi, Giancarlo / Hartung, Hans-Peter / Soelberg Sørensen, Per / Thompson, Alan J / Vermersch, Patrick / Gold, Ralf / Montalban, Xavier. ·Multiple Sclerosis Centre of Catalonia (Cemcat), Department of Neurology-Neuroimmunology, Vall d'Hebron University Hospital, Barcelona, Spain/Preventive Medicine and Epidemiology Department, Vall d'Hebron University Hospital, Barcelona, Spain sotero@cem-cat.org. · Multiple Sclerosis Centre of Catalonia (Cemcat), Department of Neurology-Neuroimmunology, Vall d'Hebron University Hospital, Barcelona, Spain. · Neurological Department, Institute of Experimental Neurology (INSPE), Scientific Institute Hospital San Raffaele, University Vita-Salute San Raffaele, Milan, Italy. · Department of Neurology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany. · Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. · Department of Brain Repair & Rehabilitation, Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK. · Université Lille, INSERM, CHU Lille, Lille Inflammation Research International Center (LIRIC) UMR 995, Lille, France. · Department of Neurology, Ruhr University, St. Josef-Hospital, Bochum, Germany. ·Mult Scler · Pubmed #27207462.

ABSTRACT: BACKGROUND AND OBJECTIVES: Treatment of spasticity poses a major challenge given the complex clinical presentation and variable efficacy and safety profiles of available drugs. We present a systematic review of the pharmacological treatment of spasticity in multiple sclerosis (MS) patients. METHODS: Controlled trials and observational studies were identified. Scientific evidence was evaluated according to pre-specified levels of certainty. RESULTS: The evidence supports the use of baclofen, tizanidine and gabapentin as first-line options. Diazepam or dantrolene could be considered if no clinical improvement is seen with the previous drugs. Nabiximols has a positive effect when used as add-on therapy in patients with poor response and/or tolerance to first-line oral treatments. Despite limited evidence, intrathecal baclofen and intrathecal phenol show a positive effect in severe spasticity and suboptimal response to oral drugs. CONCLUSION: The available studies on spasticity treatment offer some insight to guide clinical practice but are of variable methodological quality. Large, well-designed trials are needed to confirm the effectiveness of antispasticity agents and to produce evidence-based treatment algorithms.

18 Review Steering through complexity: management approaches in multiple sclerosis. 2016

Cree, Bruce A C / Hartung, Hans-Peter. ·aDepartment of Neurology, Multiple Sclerosis Center, University of California, San Francisco, California, USA bDepartment of Neurology and Center for Neuropsychiatry, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany. ·Curr Opin Neurol · Pubmed #27058222.

ABSTRACT: PURPOSE OF REVIEW: This review evaluates current and late-phase developing therapies for multiple sclerosis in regard to therapeutic efficacy and patient safety in light of recent published and presented observations from 2015. RECENT FINDINGS: We describe data that provide supportive evidence for comparisons of therapeutic efficacy of multiple sclerosis therapies and review available data on rare but serious adverse events associated with these therapies. SUMMARY: Serious adverse events that are sometimes rare and unpredictable may substantially alter current approaches to multiple sclerosis treatments. New therapies that have proved superior effects compared with older therapies will also impact multiple sclerosis treatment practice in the near future.

19 Review Optic neuritis as a phase 2 paradigm for neuroprotection therapies of multiple sclerosis: update on current trials and perspectives. 2016

Aktas, Orhan / Albrecht, Philipp / Hartung, Hans-Peter. ·Department of Neurology, Medical Faculty, Heinrich Heine University Düsseldorf, Germany. ·Curr Opin Neurol · Pubmed #27035900.

ABSTRACT: PURPOSE OF REVIEW: In multiple sclerosis as the most common inflammatory demyelinating disease in Western countries, major therapeutic success has been achieved with regard to strategies targeting immunological master switches. These approaches effectively reduce inflammatory disease activity but fail to address ongoing neurodegeneration or disturbed regeneration. However, intense research efforts investigating molecular mechanisms of disease have identified 'druggable' targets for prevention of inflammatory neurodegeneration and disturbed regeneration. This review covers recent developments in clinical trials using optic neuritis as a model for screening such neuroprotective and neuroregenerative therapeutic approaches. RECENT FINDINGS: Optic neuritis has been used in a series of recent pilot studies investigating the effects of erythropoietin, simvastatin, autologous mesenchymal stem cells, phenytoin, as well as blockade of LINGO-1 (opicinumab). Of note, these studies applied novel outcome measures related to function and structure of the visual pathway, including optical coherence tomography, full-field visual-evoked potentials, multifocal visual-evoked potential, high as well as low-contrast visual acuity. Comparison of these different approaches reveals novel insights into short-term evolution of neurobiological effects during optic neuritis and the window of opportunity for therapeutic interventions. SUMMARY: Translation of neuroprotective and neuroregenerative approaches to clinical reality represents a huge challenge. Optic neuritis as a prototypic autoimmune demyelinating disease offers an option for testing new therapies targeting key deleterious processes in multiple sclerosis.

20 Review Recent achievements in stem cell-mediated myelin repair. 2016

Jadasz, Janusz Joachim / Lubetzki, Catherine / Zalc, Bernard / Stankoff, Bruno / Hartung, Hans-Peter / Küry, Patrick. ·aDepartment of Neurology, Medical Faculty, Heinrich-Heine-University of Düsseldorf, Düsseldorf, Germany bSorbonne Universités UPMC Univ Paris 06, UMR_S 1127, ICM-GHU Pitié-Salpêtrière cInserm U1127, F-75013 dCNRS UMR7225, F-75013 eAssistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière and Hôpital Saint-Antoine, Paris, France. ·Curr Opin Neurol · Pubmed #27035898.

ABSTRACT: PURPOSE OF REVIEW: Following the establishment of a number of successful immunomodulatory treatments for multiple sclerosis, current research focuses on the repair of existing damage. RECENT FINDINGS: Promotion of regeneration is particularly important for demyelinated areas with degenerated or functionally impaired axons of the central nervous system's white and gray matter. As the protection and generation of new oligodendrocytes is a key to the re-establishment of functional connections, adult oligodendrogenesis and myelin reconstitution processes are of primary interest. Moreover, understanding, supporting and promoting endogenous repair activities such as mediated by resident oligodendroglial precursor or adult neural stem cells are currently thought to be a promising approach toward the development of novel regenerative therapies. SUMMARY: This review summarizes recent developments and findings related to pharmacological myelin repair as well as to the modulation/application of stem cells with the aim to restore defective myelin sheaths.

21 Review Repair strategies for multiple sclerosis: challenges, achievements and perspectives. 2016

Stankoff, Bruno / Jadasz, Janusz Joachim / Hartung, Hans-Peter / Küry, Patrick / Zalc, Bernard / Lubetzki, Catherine. ·aSorbonne Universités UPMC Univ Paris 06, UMR_S 1127, ICM-GHU Pitié-Salpêtrière bINSERM U1127 cCNRS UMR7225 dAssistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière and Hôpital Saint-Antoine, Paris, France eDepartment of Neurology, Medical Faculty, Heinrich-Heine-University of Düsseldorf, Düsseldorf, Germany. ·Curr Opin Neurol · Pubmed #27035897.

ABSTRACT: PURPOSE OF REVIEW: Despite major progress in multiple sclerosis (MS) treatment, to date, accumulation of irreversible clinical disability is not sufficiently prevented with immunotherapies. In this context, repair strategies aimed at reducing axonal damage are becoming a very active field of preclinical and clinical research. RECENT FINDINGS: Improved understanding of the cellular and molecular mechanisms of myelin repair, together with the emergence of new therapeutic candidates are paving the way for novel therapeutic strategies in MS. In parallel, there is a very active development of imaging methods to assess lesions ongoing remyelination that are crucially needed to evaluate therapeutic efficacy. SUMMARY: The current development of a very dynamic and multidisciplinary research on remyelination should accelerate the development of myelin repair strategies in MS, to prevent disability progression.

22 Review Disease-modifying therapies and infectious risks in multiple sclerosis. 2016

Winkelmann, Alexander / Loebermann, Micha / Reisinger, Emil C / Hartung, Hans-Peter / Zettl, Uwe K. ·Department of Neurology, University of Rostock, Gehlsheimer Strasse 20, 18147 Rostock, Germany. · Department of Tropical Medicine and Infectious Diseases, University of Rostock, Ernst-Heydemann-Strasse 6, 18057 Rostock, Germany. · Department of Neurology, Heinrich Heine University Düsseldorf, Moorenstrasse 5, 40225 Düsseldorf, Germany. ·Nat Rev Neurol · Pubmed #26943779.

ABSTRACT: Immunomodulatory and immunosuppressive treatments for multiple sclerosis (MS) are associated with an increased risk of infection, which makes treatment of this condition challenging in daily clinical practice. Use of the expanding range of available drugs to treat MS requires extensive knowledge of treatment-associated infections, risk-minimizing strategies and approaches to monitoring and treatment of such adverse events. An interdisciplinary approach to evaluate the infectious events associated with available MS treatments has become increasingly relevant. In addition, individual stratification of treatment-related infectious risks is necessary when choosing therapies for patients with MS, as well as during and after therapy. Determination of the individual risk of infection following serial administration of different immunotherapies is also crucial. Here, we review the modes of action of the available MS drugs, and relate this information to the current knowledge of drug-specific infectious risks and risk-minimizing strategies.

23 Review Advances in and Algorithms for the Treatment of Relapsing-Remitting Multiple Sclerosis. 2016

Ingwersen, Jens / Aktas, Orhan / Hartung, Hans-Peter. ·Department of Neurology, Medical Faculty, University Hospital, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. · Department of Neurology, Medical Faculty, University Hospital, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. hans-peter.hartung@uni-duesseldorf.de. ·Neurotherapeutics · Pubmed #26701666.

ABSTRACT: Treatment options in relapsing-remitting multiple sclerosis have increased considerably in recent years; currently, a dozen different preparations of disease-modifying therapies are available and some more are expected to be marketed soon. For the treating neurologist this broad therapeutic repertoire not only greatly improves individualized management of the disease, but also makes choices more complex and difficult. A number of factors must be considered, including disease activity and severity, safety profile, and patient preference. We here discuss the currently existing options and suggest treatment algorithms for managing relapsing-remitting multiple sclerosis.

24 Review [Current aspects of therapy conversion for multiple sclerosis]. 2015

Kolber, P / Luessi, F / Meuth, S G / Klotz, L / Korn, T / Trebst, C / Tackenberg, B / Kieseier, B / Kümpfel, T / Fleischer, V / Tumani, H / Wildemann, B / Lang, M / Flachenecker, P / Meier, U / Brück, W / Limmroth, V / Haghikia, A / Hartung, H-P / Stangel, M / Hohlfeld, R / Hemmer, B / Gold, R / Wiendl, H / Zipp, F. ·Klinik und Poliklinik für Neurologie, Forschungszentrum Translationale Neurowissenschaften (FTN), Forschungszentrum für Immuntherapie (FZI), Rhine Main Neuroscience Network (rmn2), Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Langenbeckstr. 1, 55101, Mainz, Deutschland. · Klinik und Poliklinik für Neurologie, Forschungszentrum Translationale Neurowissenschaften (FTN), Forschungszentrum für Immuntherapie (FZI), Rhine Main Neuroscience Network (rmn2), Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Langenbeckstr. 1, 55101, Mainz, Deutschland. luessi@uni-mainz.de. · Klinik für Allgemeine Neurologie, Universitätsklinikum Münster, Münster, Deutschland. · Neurologische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München; Munich Cluster for Systems Neurology (SyNergy), München, Deutschland. · Klinik für Neurologie, Medizinische Hochschule Hannover, Hannover, Deutschland. · Klinik für Neurologie, Klinische Neuroimmunologie, Universitätsklinikum Gießen und Marburg, Marburg, Deutschland. · Neurologische Klinik, Universitätsklinikum der Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Deutschland. · Institut für Klinische Neuroimmunologie, Klinikum der Universität München, Munich Cluster for Systems Neurology (SyNergy), München, Deutschland. · Klinik für Neurologie, Universitätsklinikum Ulm, Ulm, Deutschland. · Neurologische Klinik, Universitätsklinikum Heidelberg, Heidelberg, Deutschland. · NeuroPoint Patientenakademie, Ulm, Deutschland. · Neurologisches Rehabilitationszentrum Quellenhof, Bad Wildbad, Deutschland. · NeuroCentrum, Grevenbroich, Deutschland. · Abtl. Neuropathologie, Universitätsmedizin Göttingen der Georg-August-Universität Göttingen, Göttingen, Deutschland. · Klinik für Neurologie und Palliativmedizin, Kliniken der Stadt Köln, Köln, Deutschland. · St. Josef-Hospital, Universitätsklinikum der Ruhr-Universität Bochum, Bochum, Deutschland. · Abt. Klinische Neuroimmunologie und Neurochemie, Klinik für Neurologie, Medizinische Hochschule Hannover, Zentrum für Systemische Neurowissenschaften Hannover (ZSN), Hannover, Deutschland. ·Nervenarzt · Pubmed #26269289.

ABSTRACT: In recent years the approval of new substances has led to a substantial increase in the number of course-modifying immunotherapies available for multiple sclerosis. Therapy conversion therefore represents an increasing challenge. The treatment options sometimes show complex adverse effect profiles and necessitate a long-term and comprehensive monitoring. This article presents an overview of therapy conversion of immunotherapies for multiple sclerosis in accordance with the recommendations of the Disease-Related Competence Network for Multiple Sclerosis and the German Multiple Sclerosis Society as well as the guidelines on diagnostics and therapy for multiple sclerosis of the German Society of Neurology and the latest research results. At the present point in time it should be noted that no studies have been carried out for most of the approaches for therapy conversion given here; however, the recommendations are based on theoretical considerations and therefore correspond to recommendations at the level of expert consensus, which is currently essential for the clinical daily routine.

25 Review Dimethyl fumarate in relapsing-remitting multiple sclerosis: rationale, mechanisms of action, pharmacokinetics, efficacy and safety. 2015

Dubey, Duvyanshu / Kieseier, Bernd C / Hartung, Hans P / Hemmer, Bernhard / Warnke, Clemens / Menge, Til / Miller-Little, William A / Stuve, Olaf. ·UT Southwestern, Dallas, TX, USA. ·Expert Rev Neurother · Pubmed #25800129.

ABSTRACT: Dimethyl fumarate (DMF), a fumaric acid ester, is a new orally available disease-modifying agent that was recently approved by the US FDA and the EMA for the management of relapsing forms of multiple sclerosis (MS). Fumaric acid has been used for the management of psoriasis, for more than 50 years. Because of the known anti-inflammatory properties of fumaric acid ester, DMF was brought into clinical development in MS. More recently, neuroprotective and myelin-protective mechanism actions have been proposed, making it a possible candidate for MS treatment. Two Phase III clinical trials (DEFINE, CONFIRM) have evaluated the safety and efficacy of DMF in patients with relapsing-remitting MS. Being an orally available agent with a favorable safety profile, it has become one of the most commonly prescribed disease-modifying agents in the USA and Europe.

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