Sven Schippling

University of Zurich, Zürich, Zurich, Switzerland

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Publications (58)253.6 Total impact

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    ABSTRACT: Neuromyelitis optica (NMO) is an inflammatory autoimmune disease of the central nervous system that preferentially targets the optic nerves and spinal cord. The clinical presentation may suggest multiple sclerosis (MS), but a highly specific serum autoantibody against the astrocytic water channel aquaporin-4 present in up to 80% of NMO patients enables distinction from MS. Optic neuritis may occur in either condition resulting in neuro-anatomical retinal changes. Optical coherence tomography (OCT) has become a useful tool for analyzing retinal damage both in MS and NMO. Numerous studies showed that optic neuritis in NMO typically results in more severe retinal nerve fiber layer (RNFL) and ganglion cell layer thinning and more frequent development of microcystic macular edema than in MS. Furthermore, while patients' RNFL thinning also occurs in the absence of optic neuritis in MS, subclinical damage seems to be rare in NMO. Thus, OCT might be useful in differentiating NMO from MS and serve as an outcome parameter in clinical studies. © The Author(s), 2015.
    Multiple Sclerosis 02/2015; · 4.86 Impact Factor
  • Proceedings of the XII International Congress of Neuroimmunology, Journal of Neuroimmunology; 10/2014
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    ABSTRACT: Progressive multifocal leukoencephalopathy is a currently untreatable infection of the brain. Here, we demonstrate in 2 patients that treatment with interleukin 7, JC polyomavirus (JCV) capsid protein VP1, and a Toll-like receptor 7 agonist used as adjuvant, was well tolerated, and showed a very favorable safety profile and unexpected efficacy that warrant further investigation.
    Clinical Infectious Diseases 09/2014; · 9.42 Impact Factor
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    ABSTRACT: Optic neuritis is an inflammatory optic neuropathy that affects many patients with multiple sclerosis (MS) at some point during their disease course. Differentiation of acute episodes of MS-associated optic neuritis from other autoimmune and inflammatory optic neuropathies is vital for treatment choice and further patient management, but is not always straightforward. Over the past decade, a number of new imaging, laboratory and electrophysiological techniques have entered the clinical arena. To date, however, no consensus guidelines have been devised to specify how and when these techniques can be most rationally applied for the diagnostic work-up of patients with acute optic neuritis. In this article, we review the literature and attempt to formulate a consensus for the investigation of patients with acute optic neuritis, both in standard care and in research with relevance to clinical treatment trials.
    Nature Reviews Neurology 07/2014; · 15.52 Impact Factor
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    ABSTRACT: Retinal optical coherence tomography (OCT) permits quantification of retinal layer atrophy relevant to assessment of neurodegeneration in multiple sclerosis (MS). Measurement artefacts may limit the use of OCT to MS research.
    Multiple Sclerosis 06/2014; · 4.86 Impact Factor
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    ABSTRACT: Neuromyelitis optica (NMO, Devic's syndrome), long considered a clinical variant of multiple sclerosis, is now regarded as a distinct disease entity. Major progress has been made in the diagnosis and treatment of NMO since aquaporin-4 antibodies (AQP4-Ab; also termed NMO-IgG) were first described in 2004. In this review, the Neuromyelitis Optica Study Group (NEMOS) summarizes recently obtained knowledge on NMO and highlights new developments in its diagnosis and treatment, based on current guidelines, the published literature and expert dis-cussion at regular NEMOS meetings. Testing of AQP4-Ab is essential and is the most important test in the diagnostic work-up of suspected NMO, and helps to distinguish NMO from other autoimmune diseases. Furthermore, AQP4-Ab testing has expanded our knowledge of the clinical pre-sentation of NMO spectrum disorders (NMOSD). In addition, imaging techniques, particularly magnetic reso-nance imaging of the brain and spinal cord, are obligatory in the diagnostic workup. It is important to note that brain lesions in NMO and NMOSD are not uncommon, do not rule out the diagnosis, and show characteristic patterns. Other imaging modalities such as optical coherence tomography are proposed as useful tools in the assessment of retinal damage. Therapy of NMO should be initiated early. Azathioprine and rituximab are suggested as first-line treatments, the latter being increasingly regarded as an established therapy with long-term efficacy and an acceptable safety profile in NMO patients. Other immu-nosuppressive drugs, such as methotrexate, mycophenolate mofetil and mitoxantrone, are recommended as second-line treatments. Promising new therapies are emerging in the form of anti-IL6 receptor, anti-complement or anti-AQP4-Ab biologicals.
    Journal of Neurology 01/2014; 261(1):1-16. · 3.84 Impact Factor
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    ABSTRACT: Neuromyelitis optica (NMO, Devic's syn-drome), long considered a clinical variant of multiple sclerosis, is now regarded as a distinct disease entity. Major progress has been made in the diagnosis and treatment of NMO since aquaporin-4 antibodies (AQP4-Ab; also termed NMO-IgG) were first described in 2004. In this review, the Neuromyelitis Optica Study Group (NEMOS) summarizes recently obtained knowledge on NMO and highlights new developments in its diagnosis and treatment, based on current guidelines, the published literature and expert dis-cussion at regular NEMOS meetings. Testing of AQP4-Ab is essential and is the most important test in the diagnostic work-up of suspected NMO, and helps to distinguish NMO from other autoimmune diseases. Furthermore, AQP4-Ab testing has expanded our knowledge of the clinical pre-sentation of NMO spectrum disorders (NMOSD). In addition, imaging techniques, particularly magnetic reso-nance imaging of the brain and spinal cord, are obligatory in the diagnostic workup. It is important to note that brain lesions in NMO and NMOSD are not uncommon, do not rule out the diagnosis, and show characteristic patterns. Other imaging modalities such as optical coherence tomography are proposed as useful tools in the assessment of retinal damage. Therapy of NMO should be initiated early. Azathioprine and rituximab are suggested as first-line treatments, the latter being increasingly regarded as an established therapy with long-term efficacy and an acceptable safety profile in NMO patients. Other immu-nosuppressive drugs, such as methotrexate, mycophenolate Members of Neuromyelitis Optica Study Group (NEMOS) are listed in the appendix.
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    ABSTRACT: Progressive multifocal leukoencephalopathy (PML) is the most common clinical presentation of JC virus-associated CNS disease and has emerged as a major safety concern in multiple sclerosis patients treated with the monoclonal antibody natalizumab. Here we report clinical, radiological and histological findings of a case of cerebellar granule cell neuronopathy (GCN), a JCV-associated CNS disease, so far unreported amongst patients treated with natalizumab. GCN should be considered as a JCV CNS manifestation in patients with newly developed, progressive cerebellar signs under treatment with natalizumab, especially in cases where cerebellar atrophy can be visualized by MRI. ANN NEUROL 2013. © 2013 American Neurological Association.
    Annals of Neurology 07/2013; · 11.91 Impact Factor
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    ABSTRACT: Multiple sclerosis (MS) is a devastating inflammatory disease of the brain and spinal cord that is thought to result from an autoimmune attack directed against antigens in the central nervous system. The aim of this first-in-man trial was to assess the feasibility, safety, and tolerability of a tolerization regimen in MS patients that uses a single infusion of autologous peripheral blood mononuclear cells chemically coupled with seven myelin peptides (MOG1-20, MOG35-55, MBP13-32, MBP83-99, MBP111-129, MBP146-170, and PLP139-154). An open-label, single-center, dose-escalation study was performed in seven relapsing-remitting and two secondary progressive MS patients who were off-treatment for standard therapies. All patients had to show T cell reactivity against at least one of the myelin peptides used in the trial. Neurological, magnetic resonance imaging, laboratory, and immunological examinations were performed to assess the safety, tolerability, and in vivo mechanisms of action of this regimen. Administration of antigen-coupled cells was feasible, had a favorable safety profile, and was well tolerated in MS patients. Patients receiving the higher doses (>1 × 10(9)) of peptide-coupled cells had a decrease in antigen-specific T cell responses after peptide-coupled cell therapy. In summary, this first-in-man clinical trial of autologous peptide-coupled cells in MS patients establishes the feasibility and indicates good tolerability and safety of this therapeutic approach.
    Science translational medicine 06/2013; 5(188):188ra75. · 14.41 Impact Factor
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    ABSTRACT: Neutrophil extracellular traps (NETs) trap and kill pathogens very efficiently but also activate dendritic cells and prime T cells. Previously, we demonstrated that neutrophils are primed and circulating NETs are elevated in relapsing remitting multiple sclerosis (RRMS), a T cell-mediated autoimmune disease. Here, we demonstrate gender specific differences in circulating NETs but not in neutrophil priming in RRMS patients. Although the results from our systematic and in depth characterization of these patients argue against a major role of circulating NETs in this disease, they suggest that NETs may underlie gender-specific differences in MS pathogenesis.
    Journal of neuroimmunology 06/2013; · 2.84 Impact Factor
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    ABSTRACT: BACKGROUND: Axonal and neuronal damage are widely accepted as key events in the disease course of multiple sclerosis. However, it has been unclear to date at which stage in disease evolution neurodegeneration begins and whether neuronal damage can occur even in the absence of acute inflammatory attacks. OBJECTIVE: To characterize inner retinal layer changes in patients with clinically isolated syndrome (CIS). METHOD: 45 patients with CIS and age- and sex-matched healthy controls were investigated using spectral domain optical coherence tomography. Patients' eyes were stratified into the following categories according to history of optic neuritis (ON): eyes with clinically-diagnosed ON (CIS-ON), eyes with suspected subclinical ON (CIS-SON) as indicated by a visual evoked potential latency of >115ms and eyes unaffected by ON (CIS-NON). RESULTS: CIS-NON eyes showed significant reduction of ganglion cell- and inner plexiform layer and a topography similar to that of CIS-ON eyes. Seven eyes were characterized as CIS-SON and likewise showed significant retinal layer thinning. The most pronounced thinning was present in CIS-ON eyes. CONCLUSION: Our findings indicate that retinal pathology does occur already in CIS. Intraretinal layer segmentation may be an easily applicable, non-invasive method for early detection of retinal pathology in patients unaffected by ON.
    Multiple Sclerosis 05/2013; · 4.86 Impact Factor
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    ABSTRACT: JC virus (JCV) is an opportunistic virus known to cause progressive multifocal leukoencephalopathy. Anti-JC virus (Anti-JCV) antibody prevalence in a large, geographically diverse, multi-national multiple sclerosis (MS) cohort was compared in a cross-sectional study. Overall, anti-JCV antibody prevalence was 57.6%. Anti-JCV antibody prevalence in MS patients ranged from approximately 47% to 68% across these countries: Norway, 47.4%; Denmark, 52.6%; Israel, 56.6%; France, 57.6%; Italy, 58.3%; Sweden, 59.0%; Germany, 59.1%; Austria, 66.7% and Turkey, 67.7%. Prevalence increased with age (from 49.5% in patients < 30 years of age to 66.5% in patients ≥ 60 years of age; p < 0.0001 comparing all age categories), was lower in females than in males (55.8% versus 61.9%; p < 0.0001) and was not affected by prior immunosuppressant or natalizumab use.
    Multiple Sclerosis 03/2013; · 4.86 Impact Factor
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    ABSTRACT: BACKGROUND AND PURPOSE: Optical coherence tomography (OCT) has shown thinning of the retinal nerve fibre layer (RNFL) and total macular volume (TMV) in multiple sclerosis (MS) patients. Measures of retinal atrophy are associated with the brain parenchymal fraction (BPF) assessed by magnetic resonance imaging (MRI). However, in MS, data on the relation of OCT measures and grey and white matter volumes are contradictory. We performed a prospective cross-sectional study with a statistically pre-defined endpoint to test our hypothesis that OCT measures of neuro-axonal degeneration are related to global and partial brain atrophy in early forms of MS. METHODS AND RESULTS: Forty-four patients with clinically isolated syndrome (n = 10) or relapsing-remitting MS (n = 34; mean disease duration = 3.2 years, median EDSS = 1.5) were enrolled in the study. Peripapillary- and volumetric OCT scans of the macula were performed using latest spectral-domain OCT technology. BPF as well as white and grey matter fractions (WMF/GMF) were assessed by 1.5 Tesla MRI scans. Generalized estimating equation models adjusted for age and linear regression statistics were used to assess the association between OCT and MRI measures. RNFL thickness, TMV and age were significantly associated with BPF. RNFL thickness and TMV independently predicted WMF (P = 0.003 and P = 0.032) but not GMF (P = 0.717 and P = 0.357) when corrected for age. In contrast, age was strongly associated with GMF (P < 0.001) but not WMF. CONCLUSION: Our study suggests that, in early MS, OCT measures of retinal atrophy are related to volumetric changes in the white but not grey matter compartment as assessed by MRI. It further substantiates the association of retinal thinning and brain tissue loss in MS.
    European Journal of Neurology 01/2013; · 3.85 Impact Factor
  • European Journal of Neurology 01/2013; · 3.85 Impact Factor
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    ABSTRACT: Annualized relapse rates (ARR) in the placebo cohorts of phase-3 randomized controlled trials (RCT) of new treatments for relapsing remitting multiple sclerosis (RRMS) have decreased substantially during the last two decades. The causes of these changes are not clear. We consider a better understanding of this phenomenon essential for valuing the effects of new drugs and by designing new trials. To identify predictive factors of on-study ARR in early and recent MS trials. ARR, rate of relapse-free patients, trial start dates, baseline demographics, relapse definitions and the use of McDonald criteria were retrieved by literature research of the placebo cohorts from RRMS phase-3 trials. Predictors were estimated by univariate and multivariate regression analyses and random-effects meta-regression. In addition, regression models were calculated by the Sylvia Lawry Centre's (SLC), including individual case data from clinical trials performed until 2000. The most reliable meta-analytic results can be gained from pooled individual case data. In lack of this, random-effects meta-analyses are recommended. Data from 12 published and one unpublished trial show a decrease of ARR from 1988 to 2012 (adjR(2) = 0.807, p<0.0001). Regression models identified McDonald criteria followed by baseline mean age and the pre-study relapse rate as predictors of the ARR. The pooled individual case data (n = 505) confirmed a decrease of ARR over time. The pre-study relapse rate was the best predictor for on-study relapses. Lacking individual case data after implementation of the McDonald criteria excludes a direct comparison concerning McDonald criteria. Pre-study relapse rate was the best predictor for on-study relapse rate but failed to explain the decrease of the ARR over time alone. Higher age at baseline and the implementation of McDonald criteria were associated as well with a lowered relapse rate in the random-effects meta-regression. These findings need further clarification based on individual case data.
    PLoS ONE 11/2012; 7(11):e50347. · 3.53 Impact Factor
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    ABSTRACT: The "MS in the 21st Century" initiative was established with the purpose of (1) defining how multiple sclerosis (MS) treatment and standards of care should look in the 21st century; (2) developing a minimum standard of care across the world; and (3) motivating the broad MS community to align standards of care and challenge the current treatment paradigm. The aim was to develop a consensus statement to reach and influence the broader MS community. An expert steering group from Europe and Canada-consisting of neurologists, patient advocates, a pharmacoepidemiologist/pharmacoeconomist, and representatives from national MS centers-participated in a series of workshop-driven meetings between February 2011 and 2012. After three phases of discussions, the steering group identified that the overall vision for future care of MS should be full access to personalized treatment, with reimbursement, to achieve freedom from disease. They constructed seven overall principles that support this vision: personalized care, patient engagement, commitment to research, regulatory body education and reimbursement issues, new endpoints in clinical trials, more therapy options, and MS centers of excellence. This consensus statement outlines the key aspects of the seven principles that need to be addressed. The "MS in the 21st Century Steering Group" hopes that this consensus statement acts as a call to action for healthcare providers and decision-makers to address simultaneously the overarching principles that will guide patient management in order to improve outcomes for people with MS.
    Journal of Neurology 08/2012; 260(2). · 3.84 Impact Factor
    This article is viewable in ResearchGate's enriched format
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    ABSTRACT: BACKGROUND: Retinal nerve fibre layer (RNFL) thinning is associated with brain atrophy in multiple sclerosis (MS). An influence of optic neuritis is well documented but sparsely investigated. Recently, the retinal ganglion cell layer (GCL) has been shown to provide superior information regarding visual function and retinal neurodegeneration as compared with RNFL. OBJECTIVE: To investigate the association of white and grey matter brain volume with peripapillary RNFL and macular GCL in MS patients with and without a history of optic neuritis. METHODS: 63 patients with relapsing-remitting MS were included in a two-centre cross-sectional prospective study. All patients underwent retinal examination with spectral domain optical coherence tomography and 1.5 T MRI for determination of normalized brain volume (NBV), white matter volume (NWMV) and grey matter volume (NGMV). RESULTS: Both RNFL and GCL were associated with NBV, NWMV and NGMV in eyes without previous optic neuritis. This association is disrupted in the case of NGMV following optic neuritis. CONCLUSIONS: Both RNFL and GCL as parameters of neuro-axonal damage are comparably linked to whole brain as well as white and grey matter atrophy. An event of optic neuritis interferes with this relation, adding further damage to the optic nerve and disrupting especially an association with grey matter.
    Multiple Sclerosis 08/2012; · 4.86 Impact Factor
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    ABSTRACT: Background / Purpose: Fatigue is one of the most frequent symptoms in multiple sclerosis (MS), affecting up to 90% of patients at onset or during the course of the disease. Repetitive transcranial magnetic stimulation (rTMS) has proven efficacious for treating depression. Main conclusion: Effects on brain-derived neurotrophic factor (BDNF) serum level were observed in both TMS verum arms, prefrontal cortex (PFC) and motor cortex (MC), but not in the sham group.
    22nd Meeting of the European Neurological Society 2012; 08/2012
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    ABSTRACT: Susac syndrome, a rare but probably underdiagnosed combination of encephalopathy, hearing loss, and visual deficits due to branch retinal artery occlusion of unknown aetiology has to be considered as differential diagnosis in various conditions. Particularly, differentiation from multiple sclerosis is often challenging since both clinical presentation and diagnostic findings may overlap. Optical coherence tomography is a powerful and easy to perform diagnostic tool to analyse the morphological integrity of retinal structures and is increasingly established to depict characteristic patterns of retinal pathology in multiple sclerosis. Against this background we hypothesised that differential patterns of retinal pathology facilitate a reliable differentiation between Susac syndrome and multiple sclerosis. In this multicenter cross-sectional observational study optical coherence tomography was performed in nine patients with a definite diagnosis of Susac syndrome. Data were compared with age-, sex-, and disease duration-matched relapsing remitting multiple sclerosis patients with and without a history of optic neuritis, and with healthy controls. Using generalised estimating equation models, Susac patients showed a significant reduction in either or both retinal nerve fibre layer thickness and total macular volume in comparison to both healthy controls and relapsing remitting multiple sclerosis patients. However, in contrast to the multiple sclerosis patients this reduction was not distributed over the entire scanning area but showed a distinct sectorial loss especially in the macular measurements. We therefore conclude that patients with Susac syndrome show distinct abnormalities in optical coherence tomography in comparison to multiple sclerosis patients. These findings recommend optical coherence tomography as a promising tool for differentiating Susac syndrome from MS.
    PLoS ONE 06/2012; 7(6):e38741. · 3.53 Impact Factor
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    ABSTRACT: Retinal optical coherence tomography (OCT) is an imaging biomarker for neurodegeneration in multiple sclerosis (MS). In order to become validated as an outcome measure in multicenter studies, reliable quality control (QC) criteria with high inter-rater agreement are required. A prospective multicentre study on developing consensus QC criteria for retinal OCT in MS: (1) a literature review on OCT QC criteria; (2) application of these QC criteria to a training set of 101 retinal OCT scans from patients with MS; (3) kappa statistics for inter-rater agreement; (4) identification reasons for inter-rater disagreement; (5) development of new consensus QC criteria; (6) testing of the new QC criteria on the training set and (7) prospective validation on a new set of 159 OCT scans from patients with MS. The inter-rater agreement for acceptable scans among OCT readers (n = 3) was moderate (kappa 0·45) based on the non-validated QC criteria which were entirely based on the ophthalmological literature. A new set of QC criteria was developed based on recognition of: (O) obvious problems, (S) poor signal strength, (C) centration of scan, (A) algorithm failure, (R) retinal pathology other than MS related, (I) illumination and (B) beam placement. Adhering to these OSCAR-IB QC criteria increased the inter-rater agreement to kappa from moderate to substantial (0.61 training set and 0.61 prospective validation). This study presents the first validated consensus QC criteria for retinal OCT reading in MS. The high inter-rater agreement suggests the OSCAR-IB QC criteria to be considered in the context of multicentre studies and trials in MS.
    PLoS ONE 04/2012; 7(4):e34823. · 3.53 Impact Factor
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Publication Stats

688 Citations
253.60 Total Impact Points

Institutions

  • 2015
    • University of Zurich
      • Division of Neuropsychology
      Zürich, Zurich, Switzerland
  • 2014
    • University Hospital Zürich
      Zürich, Zurich, Switzerland
  • 2007–2014
    • University Medical Center Hamburg - Eppendorf
      • • Institute of Neuroimmunology and Clinical Multiple Sclerosis Research (inims)
      • • Department of Neurology
      Hamburg, Hamburg, Germany
  • 2013
    • Max-Delbrück-Centrum für Molekulare Medizin
      Berlín, Berlin, Germany
  • 2009–2013
    • Zentrum für Molekulare Neurobiologie Hamburg
      Hamburg, Hamburg, Germany
    • Universität Ulm
      • Clinic of Neurology
      Ulm, Baden-Wuerttemberg, Germany
  • 2012
    • Medizinische Universität Innsbruck
      • Univ.-Klinik für Neurologie
      Innsbruck, Tyrol, Austria
  • 2011
    • Charité Universitätsmedizin Berlin
      • Department of Nephrology
      Berlín, Berlin, Germany
  • 2007–2009
    • University of Hamburg
      • • Department of Diagnostic and Interventional Neuroradiology
      • • Department of Neurology
      Hamburg, Hamburg, Germany
  • 2008
    • University College London
      • Sobell Department of Motor Neuroscience and Movement Disorders
      London, ENG, United Kingdom